South-seq: DNA Sequencing for Newborn Nurseries in the South
Phase: NA
Conditions: Whole Genome Sequencing
Sponsor: University of Alabama at Birmingham

Version 1.0; 02/18/2019 
1 
Protocol 
Informed Consent Form 
Statistical Analysis Plan 
for
NCT03842995 
South-seq: Deoxyribonucleic Acid (DNA) Sequencing for 
Newborn Nurseries in the South 

Version 1.0; 02/18/2019 
2 
 
Manual of Operations and Procedures (MOOP) for DNA 
Sequencing for Newborn Nurseries in the South (SouthSeq) 
 
Principal Investigators: 
Bruce Korf, MD, PhD 
Greg Cooper, PhD 
Greg Barsh, MD 
Clinical Trial Lead: 
Maria I. Danila, MD, MSc, MSPH 
Version 4.0; 3/17/2020 
Summary of Changes from Previous Version: 
 
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
3.c.4 
Probands who met inclusion/exclusion 
criteria but passed away prior to sample 
collection can be included 
Expands the pool of eligible probands 
3.b 
Update staff roster, organization, and 
responsibilities 
Staff have been added and removed from the 
project 
Appendix 3 
Updated site consents 
Modified genomic data sharing section 
Appendix 7 
Amended enrollment, ROR (in-person) and 
(at-home) 
Amended to become more sensitive to families 
of deceased probands 

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Table of Contents 
1. 
INTRODUCTION ................................................................................................................................................................. 5 
2. 
OVERVIEW ......................................................................................................................................................................... 5 
3. 
MOOP CONTENTS AND ORGANIZATION ........................................................................................................................... 5 
3.a 
Study Flow Diagram .................................................................................................................................................. 5 
3.b 
Staff Roster, Organization and Responsibilities ......................................................................................................... 6 
3.b.1 
Organization .................................................................................................................................................... 11 
3.c 
Communication Plan ............................................................................................................................................... 18 
3.c.1 
Participant Recruitment .................................................................................................................................. 19 
3.c.2 
Proband Eligibility Criteria ............................................................................................................................... 19 
3.c.3 
Screening Log .................................................................................................................................................. 21 
3.c.4 
Participant Enrollment .................................................................................................................................... 22 
3.c.5 
Participant Retention ...................................................................................................................................... 23 
3.d 
Informed Consent and HIPAA ................................................................................................................................. 23 
3.d.1 
Informed Consent (IC) Process ........................................................................................................................ 23 
3.d.2 
Informed Consent Form .................................................................................................................................. 24 
3.e 
Study Intervention ................................................................................................................................................... 25 
3.e.1 
Participant Randomization .............................................................................................................................. 25 
3.e.2 
Implementation of the Intervention ............................................................................................................... 25 
3.e.3 
Intervention Materials .................................................................................................................................... 27 
3.e.4 
Study Outcomes .............................................................................................................................................. 28 
3.e.5 
Data Collection ................................................................................................................................................ 28 
3.f 
Participant Evaluations and Follow-Up ................................................................................................................... 31 
3.f.1 
Timeline and Visit Schedule ............................................................................................................................ 31 
3.f.2 
Scope ............................................................................................................................................................... 31 
3.f.3 
Follow-Up of Participants during the Study .................................................................................................... 43 
3.g 
Safety Reporting ...................................................................................................................................................... 44 
3.g.1 
Errors in Reporting of Results .......................................................................................................................... 44 
3.h 
Data and Safety Monitoring Board (DSMB) Activities ............................................................................................. 46 
3.h.1 
DSMB Responsibilities ..................................................................................................................................... 46 
3.h.2 
DSMB Board Process ....................................................................................................................................... 46 
3.h.3 
DSMB Meeting Format .................................................................................................................................... 46 
3.h.4 
Meeting Materials ........................................................................................................................................... 47 

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3.h.5 
DSMB Reports ................................................................................................................................................. 47 
3.h.6 
DSMB Confidentiality ...................................................................................................................................... 47 
3.i Study Compliance ........................................................................................................................................................ 47 
3.j 
Data Collection and Outcome Instruments ............................................................................................................. 48 
3.j.1 
Source Documentation .................................................................................................................................... 48 
3.j.2 
General Instructions for Completing Forms .................................................................................................... 49 
3.j.3 
Retention of Study Documentation ................................................................................................................ 49 
3.j.4 
Administrative Forms ...................................................................................................................................... 49 
3.k 
Data Management .................................................................................................................................................. 49 
3.l Reports ........................................................................................................................................................................ 50 
3.m 
Study Completion and Closeout Procedures ........................................................................................................... 50 
3.n 
Policies .................................................................................................................................................................... 51 
3.n.1 
Confidentiality Procedures .............................................................................................................................. 52 
3.n.2 
Publications ..................................................................................................................................................... 52 
3.o 
MOOP Maintenance ................................................................................................................................................ 52 
4. 
BIBLIOGRAPHY ................................................................................................................................................................ 53 

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Abbreviations 
ACMG 
American College of Medical Genetics and Genomics 
CAP/CLIA 
College of American Pathologists/Clinical Laboratory Improvement 
Amendment 
COA 
Children’s of Alabama 
CSER2 
Phase II of the Clinical Sequencing Evidence-Generating Research 
DCC 
Data Coordinating Center 
DSMB 
Data Safety Monitoring Board 
EMR 
Electronic Medical Record 
FACToR 
The Feelings About genomic Testing Results 
FAQ 
 Frequently Asked Questions 
FTP 
File Transfer Protocol 
GC 
Genetic Counselor 
GCOS 
Genetic Counseling Outcome Scale 
GCP 
Good Clinical Practice 
GG 
Genome Gateway 
HA 
HudsonAlpha 
HRQoL 
Health-Related Quality of Life 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonization of Technical Requirements 
for Pharmaceuticals for Human Use 
IRB 
Institutional Review Board 
IUGR 
(Symmetric) Intrauterine Growth Restriction 
IVH 
Intraventricular Hemorrhage 
MOOP 
Manual of Operating Procedures 
NEC 
Necrotizing Enterocolitis 
NGHRI 
National Human Genome Research Institute 
NICU 
 Neonatal Intensive Care Unit 
NIH 
National Institutes of Health 
NOA 
Notice of Award 
PHI 
Protected Health Information 
PI 
Principle Investigator 
PII 
Personally Identifiable Information 
ROP 
Retinopathy of Prematurity 
ROR 
Return of Results 
SOP 
Standard Operating Procedures 
UAB 
University of Alabama at Birmingham 
UMMC 
University of Mississippi, Medical Center 
VRC 
Variant Review Committee 
WIRB 
Western Institutional Review Board 
WGS 
Whole Genome Sequencing 

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1. INTRODUCTION 
The National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH) must ensure compliance 
with federal laws and regulations, including procedures and policies to protect the safety of all participants in the clinical 
studies it supports. In preparing to implement a study, the Principal Investigators (PI) must be aware of the terms of 
award outlined in their Notice of Award (NOA) with respect to required reporting, data and safety monitoring oversight, 
and Institutional Review Board (IRB) approval. 
The role of the manual of operating procedures (MOOP) is to facilitate consistency in the SouthSeq study implementation 
and data collection across study visits and participants. Use of the MOOP increases the likelihood that the results of the 
study will be scientifically credible and provides reassurance that participant safety and scientific integrity are closely 
monitored. 
2. OVERVIEW 
The University of Alabama at Birmingham (UAB), in partnership with HudsonAlpha (HA) Institute for Biotechnology, will 
serve as the Clinical Coordinating Center and the Data Coordinating Center for SouthSeq. The SouthSeq MOOP should 
serve as the study manual to help study staff in executing study procedures. This MOOP (and its appendices) include the 
protocol, survey forms, and site-specific Informed Consent Forms (ICFs). The SouthSeq MOOP is a dynamic document that 
will be updated throughout the study to reflect any protocol or ICFs amendments, as well as the refinement of the study 
forms and procedures. Any edits or changes to the MOOP will be noted in track changes with an updated version number 
and date; electronic copies will be sent via email to site research nurse/coordinators and archived on Freedcamp 
(freedcamp.com). 
3. MOOP CONTENTS AND ORGANIZATION 
3.a Study Flow Diagram 
Figure 1. Participant Level Timeline 

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Outcomes Assessment 
Legend 
Outcomes Survey 
Web Survey via Genome 
Gateway 
ROR visit completed in- 
person or over the phone 
 
Baseline 
Genome Sequencing 
Completed 
Return of 
results 
(ROR) visit 
ROR 
survey 
1 mo 
Post-ROR 
4 mo 
Post-ROR 
4 mo+ 
Post-ROR 
 
 
GCOS and 
FACToR 
 
 
 
Primary Outcome: Patient empowerment as measured by Genetic Counseling Outcomes Scale (GCOS) 
Secondary and Exploratory Outcomes: The Feelings About genomic Testing Results (FACToR) 
 
 
 
3.b Staff Roster, Organization and Responsibilities 
Table 1. Study Roster 
 
Name 
Role 
Address 
Phone # 
Email 
HudsonAlpha 
Michelle Amaral, 
PhD 
Data Analysis and 
Senior Scientist 
HudsonAlpha 
601 Genome Way, 
Huntsville, AL 35806 
256-327-5220 
mamaral@hudsonalpha.org 
Greg Barsh, MD, 
PhD 
PI 
HudsonAlpha 
601 Genome Way, 
Huntsville, AL 35806 
256-327-5266 
gbarsh@hudsonalpha.org 
Kevin Bowling, PhD 
Data Analysis and 
Senior Scientist 
HudsonAlpha 
601 Genome Way, 
Huntsville, AL 35806 
256-327-0494 
kbowling@hudsonalpha.org 
Meagan Cochran, 
MS, CGC* 
Genetic Counselor 
for HA (UAB/COA 
Liaison) 
HudsonAlpha 
601 Genome Way, 
Huntsville, AL 35806 
256-327-9777 
mcochran@hudsonalpha.org 
Greg Cooper, PhD 
PI 
HudsonAlpha 
601 Genome Way, 
Huntsville, AL 35806 
256-327-9490 
gcooper@hudsonalpha.org 
Kelly East, MS, CGC 
Lead Genetic 
Counselor for HA 
HudsonAlpha 
601 Genome Way, 
Huntsville, AL 35806 
256-327-0461 
keast@hudsonalpha.org 
 
Randomization 

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Candice Finnila, 
PhD# 
Clinical Project 
Manager and Data 
Analysis 
HudsonAlpha 
601 Genome Way, 
Huntsville, AL 35806 
256-327-9839 
cfinnila@hudsonalpha.org 
David Gray, MS 
Bioinformatics 
HudsonAlpha 
601 Genome Way, 
Huntsville, AL 35806 
256-327-9758 
dray@hudsonalpha.org 
Veronica Greve, 
MS, CGC* 
Genetic Counselor 
for HA (Women’s 
Hospital Liaison) 
HudsonAlpha 
601 Genome Way, 
Huntsville, AL 35806 
256-327-9594 
vgreve@hudsonalpha.org 
Susan Hiatt, PhD 
Data Analysis and 
Senior Scientist 
HudsonAlpha 
601 Genome Way, 
Huntsville, AL 35806 
256-327-0932 
shiatt@hudsonalpha.org 
Adam Hott, EdD 
Genome Gateway 
Administrator 
HudsonAlpha 
601 Genome Way, 
Huntsville, AL 35806 
256-327-0574 
ahott@hudsonalpha.org 
Whitley Kelley, MS, 
CGC* 
Genetic Counselor 
for HA (UMMC 
Liaison) 
HudsonAlpha 
601 Genome Way, 
Huntsville, AL 35806 
256-327-9819 
wkelley@hudsonalpha.org 
Donald Latner, PhD 
Data Analysis and 
Senior Scientist 
HudsonAlpha 
601 Genome Way, 
Huntsville, AL 35806 
256-327-0426 
dlatner@hudsonalpha.org 
James Lawlor, MS 
Bioinformatics 
HudsonAlpha 
601 Genome Way, 
Huntsville, AL 35806 
256-327-9758 
jlawlor@hudsonalpha.org 
Michelle 
Thompson, PhD 
Data Analysis and 
Senior Scientist 
HudsonAlpha 
601 Genome Way, 
Huntsville, AL 35806 
256-327-9721 
mthompson@hudsonalpha.org 
University of Alabama at Birmingham/ Children’s of Alabama 
Fallon Brewer, MS, 
CGC 
Genetic Counselor 
University of 
Alabama at 
Birmingham 
205-934-5384 
flevine@uabmc.edu 
Waldemar Carlo, 
MD 
Neonatologist 
Children’s of 
Alabama 
WCarlo@peds.uab.edu 
Brian Sims, MD 
Neonatologist 
Children’s of 
Alabama 
BSims@peds.uab.edu 
Shirley Cosby, RN 
Research Nurse 
for UAB 
University of 
Alabama at 
Birmingham and 
Children’s of 
Alabama 
SCosby@peds.uab.edu 
Rebecca Heaven, 
MSN, PHD 
Nurse in the 
CVICU 
Children’s of 
Alabama 
Rebecca.Heaven@childrensal.or 
g 
Hannah Hightower, 
MD 
Neonatologist 
University of 
Alabama at 
Birmingham and 
Children’s of 
Alabama 
hhightower@peds.uab.edu 
(prefers email) 

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Anna Hurst, MD, 
MS 
Medical Geneticist 
University of 
Alabama at 
Birmingham 
205-934-4983 
achurst@uabmc.edu 
Jegen Kandasamy, 
MD 
Neonatologist 
University of 
Alabama at 
Birmingham and 
Children’s of 
Alabama 
Jkandasamy@peds.uab.edu 
Bruce Korf, MD, 
PhD 
PI 
University of 
Alabama at 
Birmingham 
205-934-9411 
bkorf@uabmc.edu 
Amanda Luedecke, 
MS, CGC 
Genetic counselor 
University of 
Alabama at 
Birmingham 
205-934-9500 
aluedecke@uabmc.edu 
Deborah Laney, RN 
Research Nurse 
for UAB 
University of 
Alabama at 
Birmingham and 
Children’s of 
Alabama 
dlaney@peds.uab.edu 
Tara McNair, RN 
Research Nurse 
for UAB 
University of 
Alabama at 
Birmingham and 
Children’s of 
Alabama 
tmcnair@peds.uab.edu 
Lee Ann Merin, RN 
Research Nurse 
for UAB 
University of 
Alabama at 
Birmingham and 
Children’s of 
Alabama 
205-934-0095 
lmerin@peds.uab.edu 
Ashley Moellinger, 
MSN, CPNP-AC 
CV Pediatric nurse 
practitioner, nurse 
in the CVICU 
Children’s of 
Alabama 
205-638-3450 
Ashley.Moellinger@childrensal. 
org 
Whitney Narmore 
Genetic Counselor 
Assistant 
University of 
Alabama at 
Birmingham 
205-934-5510 
wtnarmore@uabmc.edu 
UAB Clinical Trial Team 
Maria I. Danila, 
MD, MSc, MSPH 
Co-I, Clinical Trial 
Lead Investigator 
at the 
Coordinating 
Center 
University of 
Alabama at 
Birmingham Division 
of Clinical 
Immunology and 
Rheumatology, FOT 
838, Birmingham, AL, 
35294 
205-975-1961 
mdanila@uabmc.edu 
Jeff Foster, MPH 
Clinical Trial 
Project Manager 
University of 
Alabama at 
Birmingham Division 
205-996-6086 
pjfoster@uabmc.edu 

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of Clinical 
Immunology and 
Rheumatology, FOT 
820, Birmingham, AL, 
35294 
Nicole Ledwon 
Clinical Trial 
Administrative 
Assistant 
University of 
Alabama at 
Birmingham Division 
of Clinical 
Immunology and 
Rheumatology, FOT 
820, Birmingham, AL, 
35294 
nledwon@uabmc.edu 
Amy Mudano, MPH 
University of 
Alabama at 
Birmingham Division 
of Clinical 
Immunology and 
Rheumatology, FOT 
820, Birmingham, AL, 
35294 
amymudano@uabmc.edu 
Josh Melnick, MPH 
Clinical Trial Study 
Coordinator 
University of 
Alabama at 
Birmingham Division 
of Clinical 
Immunology and 
Rheumatology, FOT 
820, Birmingham, AL, 
35294 
205-975-0583 
jmelnick@uabmc.edu 
David Redden, PhD 
Biostatistician 
University of 
Alabama at 
Birmingham 
205-975-9165 
dredden@uab.edu 
Kenneth Saag, MD, 
MSc 
Co-I 
University of 
Alabama at 
Birmingham Division 
of Clinical 
Immunology and 
Rheumatology, FOT 
820, Birmingham, AL, 
35294 
205-996-9784 
ksaag@uabmc.edu 
University of Louisville 
Alex Asamoah, MD 
Medical Geneticist 
University of 
Louisville 
Alexander.asamoah@louisville.e 
du 
Kyle Brothers, MD, 
PhD 
Co-I 
University of 
Louisville 
kyle.brothers@louisville.edu 

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Sara Deans, RN 
Primary Nurse 
Coordinator 
Contact 
University of 
Louisville 
Sarah.deans@louisville.edu 
Kelly Jackson, MS, 
CGC 
Genetic Counselor 
University of 
Louisville 
Kelly.jackson@louisville.edu 
Kristen Lee 
Gossett, BS, CCRC 
Team Leader for 
Nurse 
Coordinators 
University of 
Louisville 
Kristen.lee@louisville.edu 
Jennifer Nason, RN 
Supporting Nurse 
Coordinator 
University of 
Louisville 
Jennifer.nason@louisville.edu 
Carla Rich, MA 
Research 
Coordinator 
University of 
Louisville 
carla.rich@louisville.edu 
Josie Timmons 
Site 
Administrative 
Coordinator 
University of 
Louisville 
josie.timmons@louisville.edu 
University of Mississippi Medical Center 
Laura Hendon, MS, 
CGC 
Site Genetic 
Counselor for 
UMMC 
University of 
Mississippi Medical 
Center (UMMC) 
601-815-4487 
lhendon@umc.edu 
Renate Savich, MD, 
FAAP 
Neonatologist, 
UMMC Site PI 
University of 
Mississippi Medical 
Center (UMMC) 
2500 North State 
Street Jackson, MS 
39216 
601-815-7158 
rsavich@umc.edu 
Carly Tuura, RN 
NICU Research 
Nurse Coordinator 
University of 
Mississippi Medical 
Center (UMMC) 
601-862-8116 
(cell) 
ctuura@umc.edu 
Elizabeth White 
Researcher 
(Pediatrics and 
Neonatology) 
University of 
Mississippi Medical 
Center (UMMC) 
601-815-4078 
elwhite@umc.edu 
Heather Williams, 
RN 
Research Nurse 
University of 
Mississippi Medical 
Center (UMMC) 
601-815-3070 
hbarth@umc.edu 
University of Utah 
Sara Knight, PhD 
Co-I 
University of Utah 
sara.knight@hsc.utah.edu 
Woman’s Hospital (Baton Rouge) 
Kelly Laborde, RN 
Research Nurse 
for Woman’s 
Hospital 
Woman’s Hospital 
(Baton Rouge) 
100 Woman’s Way 
Baton Rouge, LA 
70817 
kelly.laborde@womans.org 
Steven B. Spedale, 
MD FAAP 
Neonatologist, 
Woman’s Hospital 
Site PI 
Woman’s Hospital 
(Baton Rouge) 
100 Woman’s Way 
Baton Rouge, LA 
70817 
225-928-2555 
steve.spedale@infamedics.com 

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Hillary Janani, MS, 
CGC 
Site Genetic 
Counselor for 
Woman’s Hospital 
Woman’s Hospital 
(Baton Rouge) 
100 Woman’s Way 
Baton Rouge, LA 
70817 
225-924-8310 
Hillary.janani@womans.org 
Children’s Hospital of New Orleans 
Hannah 
Meddaugh, 
MGCS,LCGC 
Genetic Counselor 
Children’s Hospital of 
New Orleans 
200 Henry Clay Ave, 
New Orleans, LA 
70118 
504-896-9254 
Hannah.Meddaugh@lcmchealth 
.org 
Jessica Patrick- 
Esteve, MD, MSPH 
Neonatologist, 
Children’s NOLA 
Site PI 
Children’s Hospital of 
New Orleans 
200 Henry Clay Ave, 
New Orleans, LA 
70118 
jpatri@lsuhsc.edu 
Marla Johnston, 
RN, MSN 
Research nurse at 
Children’s 
Hospital New 
Orleans 
Children’s Hospital of 
New Orleans 
200 Henry Clay Ave, 
New Orleans, LA 
70118 
504-896-9718 
Marla.Johnston@lcmchealth.org 
Anne Nuttli, MD 
NICU Fellow and 
researcher 
Children’s Hospital of 
New Orleans 
200 Henry Clay Ave, 
New Orleans, LA 
70118 
504-896-9418 
anuttl@lsuhsc.edu 
* Will be point of contact regarding results for site genetic counselors (GCs)/ neonatal intensive care unit (NICU) staff, 
study coordinator, reviewing variants, writing letters, uploading letters, assigning learning, and reviewing records 
# Point of contact for any study related questions 
3.b.1 
Organization 
In this multi-site clinical trial, sites will be supervised by HudsonAlpha and by the site PI at each respective site (UAB, the 
University of Mississippi Medical Center [UMMC], Woman’s Hospital (Baton Rouge), and Children’s Hospital of New 
Orleans) according to the established monitoring standard operating procedures (SOPs). HA, in collaboration with the 
Clinical Trials Team at UAB, will oversee the clinical trial to assure satisfactory data recording, adherence to the study 
protocol, and Good Clinical Practice (GCP), as well as monitor recruitment utilizing reports generated by the 
physician/team leaders at each site. The staff listed in the study roster will be responsible for all aspects of the clinical 
trial. This includes but is not limited to the following: 
• 
Finalizing the study protocol and protocol modifications 
• 
Development of the Manual of Operating Procedures (MOOP) and its maintenance 
• 
Participant randomization 
• 
Development and implementation of the data flow and data tracking 
• 
Development of procedures for data entry, error identification, and error correction 
• 
Quality control procedures 
• 
Submitting for Internal Review Board (IRB) review and approval 

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• 
Creating reports - enrollment, participant status (e.g., withdrawals) 
• 
Maintaining the study binder (regulatory and clinical documents) 
o ICF and W9 form will be uploaded to genome gateway and hardcopies will be stored in the hardcopy 
study binder 
o All other forms can be maintained within the electronic study binder or on Genome Gateway 
• 
Preparation of all study materials: recruitment materials, tracking documents, official reports 
• 
Identifying, recruiting, screening, and enrolling participants 
• 
Obtaining ICF from each participant 
• 
Protecting participants' rights 
• 
Collecting study data and following participants through study completion 
• 
Compliance and accountability with the administration of the study intervention 
• 
Communicating questions, concerns, and/or observations to the PIs 
All of the above activities will be carried out by the SouthSeq team on a weekly basis, or more frequently as needed, and 
will be monitored by the PIs and co-investigators. In the event a problem is identified by either study site PI or staff, a 
teleconference/webinar will be scheduled to review the issue. These teleconferences/webinars will be organized by 
Candice Finnila, PhD, SouthSeq Clinical Project Manager, and specific staff as designated by Dr. Finnila. Organized 
teleconferences/webinars will include discussions of overall recruitment status and identified barriers to recruitment 
experienced by the site with the study teams at HA and UAB. If the site study team members are unable to participate on 
the teleconference call, information about recruitment barriers and recruitment status can be shared via email in 
advance of the clinical trials team weekly meeting. 
The study will be conducted under the auspices of the IRBs at UAB, UMMC, Woman’s Hospital (Baton Rouge), and 
Children’s Hospital of New Orleans. UAB’s IRB will serve as the main reviewer in accordance with the reliance 
agreements. Before initiating the clinical trial within the SouthSeq study, the site PI will have written and dated full 
approval from the responsible IRB for the protocol. In the event changes/amendments to the protocol or other study 
materials (e.g. participant-related documents, study advertisements) are made, approved amendments will be submitted 
to the respective sites, as notification of changes. The UAB IRB has approved Genome Gateway as the electronic data 
entry system. 
Site investigators will also promptly report to Dr. Finnila all protocol deviations in the study, all unanticipated problems 
involving risks to human subjects or others, and any protocol deviations, to eliminate immediate hazards to subjects. The 
UAB IRB will be promptly notified when necessary. 
(1) HudsonAlpha (HA) Institute for Biotechnology 
The HudsonAlpha Institute for Biotechnology is a non-profit research institute located in Huntsville, AL. As part of the 
SouthSeq project, HudsonAlpha is responsible for intake of participant samples, with follow through to development of a 
College of American Pathologists/Clinical Laboratory Improvement Amendment (CAP/CLIA)-certified genetic Sanger 
report and a family-friendly report (see appendix 1) created by the genetic counselors (GC) at HudsonAlpha that will be 
returned to the proband’s (neonate being sequenced) family. More specifically, HudsonAlpha is charged with the 
handling and processing of proband samples, isolating genomic DNA, preparing sequencing libraries, conducting whole 
genome sequencing (WGS), completing genomic data analysis, curating and annotating identified genetic variation, 
interpreting genetic variants, sending variants for validation in a CAP/CLIA-certified independent laboratory, overseeing 
and leading variant review committee (VRC) meetings, and writing genetic counseling letters that will accompany delivery 
of technical Sanger reports to participant families. 

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Genome Gateway 
Genome Gateway, a web interface developed by HudsonAlpha, will be used to facilitate communication, education and 
the sharing of information between the study staff and study participants. Genome Gateway provides a simple user 
interface that is intuitive and easy to navigate for participants, healthcare providers, and researchers. It is hosted on a 
HIPAA-compliant platform with a secure, unique login system, physical and data security, and disaster recovery and 
backup. 
Genome Gateway was initially created to provide support to patients and healthcare providers during clinical 
appointments, including a dynamic family history tool that creates a pedigree, tailored learning articles (modules) 
assignable per individual, secure messaging and customized questionnaire deployment. Current account types are listed 
below: 
- 
Admin Account: An administrative account for the user(s) who require global access to the website, including 
access to a back-end console website used for management of functions within the user-facing site. This account 
provides the highest level of permissions and is restricted to a small number of users, who are responsible for 
addition of website content and management of the data and workflow within Genome Gateway. 
 
- 
Patient Account: An account for study participants (or parents in the case of SouthSeq). This account gives access 
to their personal settings and demographic information, allows entry of family history information, completion of 
surveys, and access to learning modules. For SouthSeq, participants can also access files and messages sent to 
them by study staff. Patients can also reply to messages. 
 
- 
Provider Account: An account for study personnel who interact with the patients as providers. This can include 
neonatologists, nurse practitioners, clinical geneticists, research study coordinators, research nurses, and GCs. 
Providers can access participant profiles (including personally identifiable information [PII]/ patient health 
information [PHI]), complete surveys regarding participants ("administered surveys"), and send messages and 
files to participants and other research staff. Providers also have access to learning modules. 
 
- 
Researcher Account: An account for study personnel who need access to de-identified data for research 
purposes, but who do not interact directly with participants. Researchers can access completed administered 
surveys, but only in a de-identified manner. Researchers can also send/receive messages to/from other study 
personnel. 
Whole Genome Sequencing (WGS) 
At least 1 mL of blood will be drawn from each newborn participant into a 4mL EDTA tube (blood collection method and 
location of venipuncture will be left up to the clinical staff, but should be combined with routine care if possible). Blood 
will be shipped as soon as possible following study enrollment/specimen collection. Blood tubes that are not shipped day 
of venipuncture will be stored at 4οC until shipment. If the newborn has had a blood transfusion, they can still be enrolled 
and a blood sample can still be collected. Isolation of genomic DNA from whole blood will be performed in the 
HudsonAlpha Clinical Services Laboratory (CSL) using the QIA symphony instrument (Qiagen). Sequencing libraries will be 
constructed from genomic DNA using the CSL's custom whole genome library preparation protocol. Sequencing will be 
completed on the Illumina HiSeq X or NovaSeq sequencing platform. DNA library fragments will be sequenced from both 
ends (paired) with a read length of 150 base pairs. WGS will be completed to an approximate depth of 30X, with 

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requirement that at least 80% of base positions reach 20X coverage. Genetic variation will be called using GATK3 (Broad 
Institute) and variants will be loaded into a custom software analysis application (Codicem, HudsonAlpha) which will 
annotate variants with relevant information in order to aid in variant curation and interpretation. Variant classification 
will be determined according to the guidelines set forth by the American College of Medical Genetics and Genomics 
(Richards et. al., 2015, PMID: 25741868). Variants that are classified as pathogenic, likely pathogenic, or of uncertain 
significance will be included in a research report and PerkinElmer, EGL-Eurofins, or HudsonAlpha CSL will perform Sanger 
confirmation, where validation will take approximately 28 days. Variants of interest to the analysts will be discussed by 
the Variant Review Committee (consisting of neonatologists, medical geneticists, nurse coordinators, GCs, research 
scientists, ethicists, etc.) to determine whether they should be returned. Variants deemed to be returnable to 
participants will be written into a genetic counseling report generated by GCs at HudsonAlpha, which, along with the 
CAP/CLIA-certified Sanger validation report, if available, will be returned to the participant family by a GC or healthcare 
provider, and placed in the proband’s medical record. 
(2) University of Alabama at Birmingham (UAB) Women & Infants Center and Children’s of 
Alabama (COA) 
Located in the largest metropolitan region in Alabama, UAB Women & Infants Center has a 120 bed level IV NICU with 
~1,500 admissions per year and is physically connected to Children’s of Alabama (COA), which has a 40 bed NICU and a 20 
bed cardiovascular ICU, with ~400 admissions per year. The Division of Neonatology is directed by Dr. Wally Carlo (UAB 
Site PI), and includes 15 attending neonatologists. The NICU is also the site of an active medical genetics consultation 
service including Dr. Anna Hurst. A chart review of 2017 UAB admissions indicated that 47% were African American and 
8% were Hispanic. 
(i) Responsibilities 
• 
Identify potential participants in the nursery or inpatient setting using the inclusion/exclusion criteria outlined in 
the study protocol 
• 
Obtain consent from interested participants 
• 
Collect W9 from parents/caregivers, so they may be paid for their participation in the clinical trial 
• 
Collect blood specimens from the enrolled proband and parents, if available 
• 
Assistance in creation and set-up of Genome Gateway account for the parents/caregivers 
• 
Direct participant (parent or caregiver) to complete baseline survey and family history questionnaire/pedigree via 
Genome Gateway 
• 
The research nurse will complete assigned surveys in Genome Gateway. These surveys are focused on 
clinical phenotypes, previous genetic testing, prenatal testing (if known) and the enrollment process. 
• 
May call parents/caregivers when surveys are not completed within specific time frames. 
• 
Ship samples to the HudsonAlpha Clinical Services Laboratory and submit them for sequencing via online portal 
• 
Schedule participant family for a return of results (ROR) appointment with a genetic counselor/healthcare 
provider based on randomization assignment. Coordinate the ROR appointment day logistics including space, 
personnel, audio recording, and asking families to complete initial follow-up survey in Genome Gateway 
• 
If travel to the site is an issue, a phone call may be scheduled to return genetic results (though this is not 
the preferred method) 
• 
Place the clinical Sanger report, along with the family-friendly genetic counseling letter in the child’s medical 
record so that clinicians have access to the finding(s) 
(3) Clinical Trials Group at UAB 

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16 
 
The clinical trials group is one of the most active academic clinical investigational programs at the UAB. The group has 
played a pivotal role in the advancement of healthcare, patient care, and access to treatments. 
(i) Responsibilities 
• 
Development of clinical trial’s objectives, design, and methods 
• 
Oversight of the scientific and technical direction of the trial 
• 
Submit and process W9’s for payment from parents/caregivers at all participating sites 
• 
Track survey completion and payments 
• 
Ensure compliance with GCP principles, quality management, and oversee monitoring systems 
• 
Ensure protocol compliance 
(4) University of Mississippi Medical Center (UMMC) 
The UMMC, located in Jackson, MS provides tertiary care for the entire state, with a 102 bed level IV NICU and ~950 
admissions per year. The Division of Neonatology and Newborn Medicine is directed by Dr. Renate Savich (UMMC site PI) 
and includes 14 neonatologists. Dr. Brian Kirmse is Chief, Division of Pediatric Genetics. A unique population is the 
Mississippi Band of Choctaw, a group of ~10,000 individuals that mostly reside in the central portion of Mississippi, and 
who are disproportionately affected by both chronic disease and congenital anomalies. The demographics of NICU 
population at this site include 41% African American, 3% Choctaw, and 3% Hispanic patients. 
(i) Responsibilities 
• 
Identify potential participants in the nursery or inpatient setting using the inclusion/exclusion criteria outlined in 
the study protocol 
• 
Obtain consent from interested participants 
• 
Collect W9 from parents/caregivers, so they may be paid for their participation in the clinical trial 
• 
Collect blood specimens from the enrolled proband and parents, if available 
• 
Assistance in creation and set-up of Genome Gateway account for the parents/caregivers 
• 
Direct participant (parent or caregiver) to complete baseline survey and family history questionnaire/pedigree via 
Genome Gateway 
• 
Research nurse will complete assigned surveys in Genome Gateway. These surveys are focused on clinical 
phenotypes, previous genetic testing, prenatal testing (if known) and the enrollment process. 
• 
May call parents/caregivers when surveys are not completed within specific time frames. 
• 
Ship samples to the HudsonAlpha Clinical Services Laboratory and submit them for sequencing via online portal 
• 
Schedule participant family for a return of results (ROR) appointment with a genetic counselor/healthcare 
provider based on randomization assignment. Coordinate ROR appointment day logistics including space, 
personnel, audio recording, and asking families to complete the baseline surveys in Genome Gateway 
• 
If travel is an issue, a phone call may be scheduled to return genetic results (though this is not the 
preferred method) 
• 
Place the clinical Sanger report along with the family-friendly genetic counseling letter in the child’s medical 
record so that clinicians will have access to the finding(s) 
(5) Woman’s Hospital (Baton Rouge) 
Located in Baton Rouge, LA Woman’s Hospital has an 84 bed Level IIIc NICU with ~1100 admissions per year. The Division 
of Neonatology is directed by Dr. Steve Spedale (Woman’s Hospital Site PI), and includes 10 attending neonatologists and 

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17 
 
11 neonatal nurse practitioners. The Genetics consultation service is directed by Dr. Duane Superneau and there is a full- 
time in-house GC, Hillary Wienpahl. The demographics of the NICU population at this site include 43% African American 
and 3% Hispanic infants. 
(i) Responsibilities 
• 
Identify potential participants in the nursery or inpatient setting using the inclusion/exclusion criteria outlined in 
the study protocol 
• 
Obtain consent from interested participants 
• 
Collect W9 from parents/caregivers, so they may be paid for their participation in the clinical trial 
• 
Collect blood specimens from the enrolled proband and parents, if available 
• 
Assistance in creation and set-up of Genome Gateway account for the parents/caregivers 
• 
Direct participant (parent or caregiver) to complete baseline survey and family history questionnaire/pedigree via 
Genome Gateway 
• 
Research nurse will complete assigned surveys in Genome Gateway. These surveys are focused on clinical 
phenotypes, previous genetic testing, prenatal testing (if known) and the enrollment process. 
• 
May call parents/caregivers when surveys are not completed within specific time frames. 
• 
Ship samples to the HudsonAlpha Clinical Services Laboratory and submit them for sequencing via online portal 
• 
Schedule participant family for a return of results (ROR) appointment with a genetic counselor/healthcare 
provider based on randomization assignment. Coordinate ROR appointment day logistics including space, 
personnel, audio recording, and asking families to complete the baseline surveys in Genome Gateway 
• 
If travel is an issue, a phone call may be scheduled to return genetic results (though this is not the 
preferred method) 
• 
Place the clinical Sanger report along with the family-friendly genetic counseling letter in the child’s medical 
record so that clinicians will have access to the finding(s) 
(6) Children’s Hospital of New Orleans 
Children’s Hospital, located in New Orleans, LA, has a 36 bed level IV NICU with ~200 admissions per year, and has a 20 
bed cardiovascular ICU, with ~65 admissions per year. The Division of Neonatology is directed by Dr. Brian Barkemeyer 
(Site PI), and includes 8 attending neonatologists through an affiliation with Louisiana State University Health Sciences 
Center – New Orleans with plans to hire 2 more neonatologists by July 2019. Through this partnership, Children’s 
Hospital trains the largest group of future neonatologists and pediatricians in Louisiana. The demographics of the NICU 
population at this site include 37% African American and 12% Hispanic infants. 
(i) Responsibilities 
• 
Identify potential participants in the nursery or inpatient setting using the inclusion/exclusion criteria outlined in 
the study protocol 
• 
Obtain consent from interested participants 
• 
Collect W9 from parents/caregivers, so they may be paid for their participation in the clinical trial 
• 
Collect blood specimens from the enrolled proband and parents, if available 
• 
Assistance in creation and set-up of Genome Gateway account for the parents/caregivers 
• 
Direct participant (parent or caregiver) to complete baseline survey and family history questionnaire/pedigree via 
Genome Gateway 

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• 
Research nurse will complete assigned surveys in Genome Gateway. These surveys are focused on clinical 
phenotypes, previous genetic testing, prenatal testing (if known) and the enrollment process. 
• 
May call parents/caregivers when surveys are not completed within specific time frames. 
• 
Ship samples to the HudsonAlpha Clinical Services Laboratory and submit them for sequencing via online portal 
• 
Schedule participant family for a return of results (ROR) appointment with a genetic counselor/healthcare 
provider based on randomization assignment. Coordinate ROR appointment day logistics including space, 
personnel, audio recording, and asking families to complete the baseline surveys in Genome Gateway 
• 
If travel is an issue, a phone call may be scheduled to return genetic results (though this is not the 
preferred method) 
• 
Place the clinical Sanger report along with the family-friendly genetic counseling letter in the child’s medical 
record so that clinicians will have access to the finding(s) 
 
(7) University of Louisville & Norton Children’s Hospital 
Norton Children’s Hospital, located in Louisville, KY provides tertiary care for much of Kentucky and Southern Indiana. 
NCH features a 101 bed level IV NICU that covers over 1100 admissions per year. The NICU is staffed by two neonatology 
groups. The University of Louisville, Division of Neonatology with its 24 neonatologists staffs the NICU at NCH, a Neonatal 
Follow-up Program, and several other NICUs in the region. Norton Children’s Neonatology with 14 neonatologists staffs 
the NICU at NCH, a High Risk Neonatology Follow-up Clinic, and several other NICUs in the region. The demographics of 
the NICU population at NCH includes 19% African American and 4% Hispanic patients. A second NICU at the University of 
Louisville Hospital offers a secondary recruitment site if needed. 
(i) Responsibilities 
• 
Identify potential participants in the nursery or inpatient setting using the inclusion/exclusion criteria outlined in 
the study protocol 
• 
Obtain consent from interested participants 
• 
Collect W9 from parents/caregivers, so they may be paid for their participation in the clinical trial 
• 
Collect blood specimens from the enrolled proband and parents, if available 
• 
Assistance in creation and set-up of Genome Gateway account for the parents/caregivers 
• 
Direct participant (parent or caregiver) to complete baseline survey and family history questionnaire/pedigree via 
Genome Gateway 
• 
Research nurse will complete assigned surveys in Genome Gateway. These surveys are focused on clinical 
phenotypes, previous genetic testing, prenatal testing (if known) and the enrollment process. 
• 
May call parents/caregivers when surveys are not completed within specific time frames. 
• 
Ship samples to the HudsonAlpha Clinical Services Laboratory and submit them for sequencing via online portal 
• 
Schedule participant family for a return of results (ROR) appointment with a genetic counselor/healthcare 
provider based on randomization assignment. Coordinate ROR appointment day logistics including space, 
personnel, audio recording, and asking families to complete the baseline surveys in Genome Gateway 
• 
If travel is an issue, a phone call may be scheduled to return genetic results (though this is not the 
preferred method) 
• 
Place the clinical Sanger report along with the family-friendly genetic counseling letter in the child’s medical 
record so that clinicians will have access to the finding(s) 

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19 
 
3.c Communication Plan 
As this protocol is currently being carried out at multiple sites (HudsonAlpha, UAB, UMMC, Woman’s Hospital (Baton 
Rouge), and Children’s Hospital of New Orleans it is strongly recommended that each site meets as a group to at a 
minimum biweekly to discuss the ongoing progress of the study. 
Topics of discussion at each meeting may include: 
• 
Recruitment progress 
• 
Enrollment and ROR progress/status 
• 
Issues or concerns with the study and possible solutions (e.g., Genome Gateway concerns) 
• 
Other study updates 
Additionally, the clinical project manager (Dr. Candice Finnila) will keep the overall study and clinical trial investigators 
informed of the weekly progress of the study work group meetings via email updates that include the following 
information: 
• 
Screening log (maintained by each site’s research nurse/coordinator and compiled by Dr. Finnila) 
• 
Consort diagram detailing number of participants enrolled (updated via Freedcamp website twice/month) 
o Including demographics and enrollment site 
o Update on the study findings to be returned (overall diagnostic rate and number of primary and 
secondary findings) 
• 
Other study updates 
• 
Review status of data collection, including pending surveys, timeliness of the data, completeness of data, and 
data elements requiring possible adjudication, verification, or further explanation. 
In addition, meetings will be conducted within and among various study working groups and personnel to discuss the on- 
going progress of the study, as well as any urgent topics. Specifically: 
• 
PI Meeting: These meetings will occur as needed and attendees include Drs. Bruce Korf, Greg Cooper, Greg Barsh, 
Candice Finnila and Kevin Bowling. This group will meet to discuss items required by the funding group and other 
high-level items that might impact the study. 
• 
SouthSeq Leadership: attendees include Drs. Bruce Korf, Greg Cooper, Greg Barsh, Maria Danila, Kevin Bowling, 
and Candice Finnila. This group meets weekly to discuss topics that require high-level decisions and involve 
direction of the study and clinical trial. 
• 
SouthSeq Operations: attendees include PIs, research nurses, GCs, and representation from the clinical trial team 
from UAB and analysis group from HudsonAlpha. These meetings will be held ad hoc for the duration of project. 
The purpose of the call is to discuss any topics that may impact multiple study sites and troubleshoot potential 
resolutions. 
• 
Clinical Trials: attendees include Dr. Maria Danila, Dr. Elizabeth Rahn, Dr. Candice Finnila, Kelly East, Dr. Kyle 
Brothers, Dr. Sara Knight, Jeff Foster, Dr. Renate Savich, Dr. David Redden, Josh Melnick, weekly for duration of 
project for the purpose of discussing the clinical trial portion of the study. Site research nurses/coordinators may 
request call-in information if they would like to attend. 
• 
GC Virtual Huddle: attendees include all HudsonAlpha GCs and site-specific GCs, bi-weekly for duration of project, 
purpose of the call is to discuss the progress of returning results, challenging cases, and trouble-shoot any genetic 
counseling issues that arise. 

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20 
 
• 
Qualitative: attendees include Dr. Sara Knight, Dr. Kyle Brothers, Carla Rich, Dr. Maria Danila, Dr. Elizabeth Rahn, 
Dr. Candice Finnila, Kelly East, Whitley Kelley, Dr. Renate Savich, Dr. Ashley Cannon, and Jaimie Richards weekly 
for the duration of project, purpose of the call is to discuss qualitative dimensions of the study including key 
informant interviews, semi-structured interviews with parents, cognitive interviews, and deliberative 
engagement events. 
• 
Education and Training: attendees include Kelly East, Dr. Elizabeth Rahn, Dr. Sara Knight and Dr. Maria Danila, bi- 
weekly until patient education and provider training materials are finalized (then this call will transition to an as- 
needed basis), purpose of the call is to discuss the progress of the development and testing of patient/provider 
education and training materials. 
• 
Variant Review Committee (VRC): attendees include medical geneticists, neonatologists, other clinical specialists, 
nurses, GCs, ethicists, research scientists, and PIs (Drs. Korf, Cooper, and Barsh). These meetings will most likely 
be held on a weekly basis, depending on the number of reports requiring discussion, and will be site specific. At 
these meetings genetic variations will be discussed in the context of clinical phenotype, and variant sign-off will 
occur. It is at a VRC meeting where decisions will be made as to what variants are returned to participant 
families, and to what extent it is believed that the genetic findings describe the participant’s phenotype. 
3.c.1 
Participant Recruitment 
The goal of SouthSeq study is to recruit and enroll 1,500 newborns (probands) with signs suggestive of a genetic disorder 
being treated at hospitals in which African Americans and rural populations are highly represented. The SouthSeq clinical 
trial will recruit and enroll parents or caregivers from 800 newborns enrolled in the parent SouthSeq study. Recruitment 
will draw from the five major pediatric institutions (UAB/Children’s of Alabama, UMMC, Woman’s Hospital (Baton 
Rouge), Children’s Hospital of New Orleans, and the University of Louisville/Norton’s Children Hospital. A central goal of 
this project is to expand the access of genomic medicine to underrepresented minorities and/or medically underserved 
communities, which feature prominently in the South. 
Families with newborns will be recruited, in addition to families with stillborn babies, directly from the four pediatric sites 
meeting the study eligibility criteria. Families can be approached perinatally and can consent to participate prior to birth. 
The inclusion and exclusion criteria will be reviewed with potential participants and the informed consent will be 
obtained by the site study coordinator. Study procedures will not begin until the signed informed consent forms have 
been obtained. Consent must be obtained from any parent/caregiver who thinks they might ever participate in the 
clinical trial. 
Study primary investigators will meet as part of a monthly operations meeting to discuss topics relevant across all 
recruitment sites. In the event a problem is identified by either study site PI or staff, a teleconference/webinar or a direct 
conversation with a PI or coordinator will be scheduled to review the issue. 
In addition to the robust set of learning available within Genome Gateway, a one-page flyer has been created to provide 
a high-level overview of the study (see Appendix 5), and will be used for participant recruitment and to help build 
awareness for the study. Basic information about the study will also be housed on the public facing website: 
hudsonalpha.org/southseq. 
 
 
3.c.2 
Proband Eligibility Criteria 
Inclusion Criteria: 

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21 
 
An infant receiving care in the nursery or other inpatient setting, e.g. surgical and/or cardiac intensive care unit during 
their first hospital admission or first 12 months of life, AND meeting one of the following criteria: 
a) A pattern of congenital anomalies consistent with a genetic, i.e, syndromic cause, and for which the primary care 
team does not know of an obvious etiology. “Obvious etiology” refers to a genetic, infectious, or environmental 
cause that has been or can be rapidly confirmed by history and/or laboratory testing, e.g. Trisomy 21, TORCH 
infection, fetal hydantoin exposure. 
b) A major medical condition such as seizures, neurological abnormality (hypotonia, hypertonia), metabolic 
abnormality, or conjugated hyperbilirubinemia for which the primary care team does not know of an obvious 
etiology. As noted above, “obvious etiology” refers to a genetic, infectious, or environmental cause that has been 
or can be rapidly confirmed by history and/or laboratory testing, e.g. intraventricular hemorrhage associated with 
significant prematurity, seizures associated with an inborn error of metabolism for which a molecular diagnosis 
can be confirmed. 
c) Parent or caregiver must be willing to participate and answer clinical trial surveys 
Exclusion Criteria: 
a) A pattern of findings and/or abnormalities consistent with known or strong suspicion for a chromosomal 
aneuploidy (Ts13, 18, 21, Monosomy X). 
b) Isolated anomalies known to have a low diagnostic yield for Mendelian causes, e.g. gastroschisis, hydronephrosis. 
c) A pattern of findings and/or abnormalities consistent with confirmed teratogenic exposures, e.g. hydantoin, 
valproate. 
d) A pattern of findings and/or abnormalities consistent with confirmed congenital infection, e.g. TORCH. 
e) Parent or caregiver is not available or willing to participate and answer clinical trial surveys** 
**Families who choose not to participate in the clinical trial (randomization and surveys) can still be enrolled in the study 
(WGS and ROR). This option will not be advertised, but if someone specifically asks if the surveys are required, it is 
acceptable to say no. 
Notes: 
1. Patients with suspected Down syndrome or life-threatening whole chromosome aneuploidies in which acute 
clinical care depends on a diagnosis, e.g. Ts13 or Ts18, will not be enrolled, but patients with congenital 
anomalies for which a clinical chromosomal microarray would otherwise be obtained may be enrolled. 
2. Patients with a history of potential teratogenic exposures or congenital infection may be eligible for inclusion if 
there are congenital anomalies and/or conditions that are not explained by the potential teratogen or infection. 
In this situation, one of the study investigators should be consulted. 
3. “Pattern of findings and/or abnormalities” refers to established principles for medical genetics, in which general 
guidelines are “2 or major congenital anomalies”, “1 major and 2 or more minor anomalies”, “1 major anomaly 
and an unexplained major medical condition”, or “1 major anomaly and a first degree relative with the same 
anomaly”, with examples (not intended to be exhaustive) indicated below. 
 
Major 
Structural malformations likely 
to require surgical intervention 
or be of significant functional 
effect 
Minor 
Physical variants that are a 
departure from normal 
development but only have a 
cosmetic effect 
Medical Conditions 
Medical conditions not explained 
by prematurity (such as NEC, 
ROP, IVH) 

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Structural brain malformations 
(holoprosencephaly, 
schizencephaly) 
Abnormal hair whorls (position or 
number -- absent, triple, multiple) 
Seizures 
Cleft lip and palate 
Abnormal fontanelles (third 
sagittal, metopic) 
Cataracts 
Severe micrognathia 
Preauricular pits or tags 
Unexplained Hypoglycemia 
Macroglossia 
Atypical ear formation or 
placement (microtia, cupped, 
crumpled, low-set) 
Conjugated (direct) 
hyperbilirubinemia 
Structural heart defect 
Epicanthal folds 
Hearing Loss (confirmed) 
Congenital diaphragmatic hernia 
Cleft/bifid uvula 
Ichthyosis 
Structural renal anomaly 
Neck webbing 
Hypotonia 
Coloboma – iris or retina 
Supernumerary nipple 
Myopathy 
Tracheoesophageal fistula 
Sacral dimple 
Arthrogryposis 
Symmetric IUGR 
Syndactyly 
Hepatic dysfunction 
Anotia 
Single transverse palmar crease 
Apnea (central or obstructive) 
Omphalocele 
Clinodactyly 
Vertebral anomalies 
Hypospadias 
Limb deficiency or shortening 
Abnormal pigmentation 
Ambiguous genitalia 
Dysmorphic findings not otherwise 
mentioned 
Biliary atresia 
Imperforate anus 
Heterotaxy 
 
3.c.3 
Screening Log 
The primary intent for completing a screening log (see appendix 11) is to report trial results and to assess the 
generalizability of findings. It is important to maintain consistency and accuracy when completing the log. Each potential 
participant will be assigned a screening ID: 
• 
UAB Screening IDs: 10001 through 10999 
• 
UMMC Screening IDs: 20001 through 20999 
• 
Woman’s Hospital (Baton Rouge) Screening IDs: 30001 through 30999 
• 
Children’s Hospital of New Orleans Screening IDs: 40001 through 40999 
• 
University of Louisville Screening IDs: 50001 through 50999 
 
It is important to complete all fields and if the proband’s parents/caregivers don’t participate it is important to complete 
a decliner survey (see appendix 2). The decliner survey can be completed post-encounter by a research nurse 
/coordinator using their judgment to determine the reason(s) for not participating. 

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23 
 
The Screening Log will only include those that are approached for participation. General information about the number of 
individuals admitted to the hospital can be collected later. 
 
Sections of Screening Log to be completed: 
• 
Proband demographics (sex, ethnicity, race) 
• 
Date of consent (if enrolled) 
• 
SouthSeq ID (if enrolled) 
• 
Eligible for enrollment (if not, provide a reason) 
• 
Completion of decliner survey (if needed) – this is optional to the family 
• 
Completion of W9 (form needed for participant payments)* 
 
 
The Screening Log will be kept by each site’s research nurse/coordinator and will be sent monthly to Dr. Finnila to 
compile a study wide list of screened participants. 
*Please make sure the participant writes legibly and is using their legal name to ensure prompt payment. 
 
3.c.4 
Participant Enrollment 
Newborns with possible congenital anomalies will be screened to determine if they satisfy inclusion and exclusion 
criteria. Parents or caregivers of the newborn (i.e. proband) will be enrolled in the clinical trial (includes WGS) once ICF is 
signed. Mothers, under 18 years or older, may consent for themselves and their children to participate. In addition, 
probands may be included that have passed away prior to sample collection. 
Consent of at least one parent/caregiver is necessary for enrollment of the proband and participation in the clinical 
trial, but if the other parent/caregiver will potentially complete any surveys it is crucial to have them sign a consent 
form, complete a W9 form, and complete the enrollment survey. Prior to enrollment the study objectives will be 
explained to potential participants. After answering questions posed by the potential participating family, and before any 
protocol-specified procedures are initiated, participants must sign the ICF. A copy of the signed and dated ICF will be 
provided to the family via Genome Gateway unless they prefer a paper copy. Basic demographic information and 
reason(s) for exclusion must be logged for all individuals who sign the ICF, but withdraw before receiving WGS. During the 
enrollment visit, the following procedures will be performed. 
• 
Review inclusion/exclusion criteria 
• 
Review, signing and noting the date Informed consent form (ICF) 
• 
Documentation date of birth (proband and parent(s)/caregiver(s)) 
• 
Documentation parent/caregiver self-reported race/ethnicity 
• 
Creation of Genome Gateway account 
• 
Collection contact information for enrolled parent/caregiver 
• 
Collection of information for a non-household contact, if participant is willing, asked in enrollment survey via 
Genome Gateway 
• 
Completion of W9 (payment for survey completion) form by any parent/caregiver who will complete a survey 
• 
Administration of the baseline survey (Site specific to determine how much help is given to participating families) 
• 
Encouraging review of initial online learning topics in Genome Gateway 

Version 1.0; 02/18/2019 
24 
 
Families that are approached but decline to participate will be asked to complete a decliner survey. The survey includes 
basic demographic information and the reason for not participating (to be completed by research nurse/coordinator) 
(see Appendix 2: Decliner Survey). The reason(s) for not participating are documented and transferred from the survey 
(or based on what the coordinator was told) to the clinical trial Screening Log. The form can be filled out at the 
coordinator’s discretion. It can be done at the time of the patient encounter or completed after depending on comfort 
level and time availability. The decliner survey will be completed on paper and uploaded to Genome Gateway. Steps for 
uploading documents to Genome Gateway can be found 3.f.2 section 1. 
 
3.c.5 
Participant Retention 
After enrollment, the site study coordinator will contact potential family participants in a variety of ways (messaging 
through Genome Gateway platform, by mail, by phone and in-person) for optimal retention. Retention efforts begin with 
recruitment and are an ongoing process and congeniality, respectfulness and friendliness in interactions with participants 
is important in this endeavor. To increase retention research the nurse/coordinator responsible for recruitment will be 
responsible for accommodating the scheduling needs of all participants. The following major principles and commonly 
used strategies to maximize retention and minimize loss to follow-up will be employed during the trial, some examples 
are included here: 
• 
Stressing the idea that participants have an active role in the research and are part of the research team 
• 
Enhancing participants understanding of the study’s mission and the protocol 
• 
Building relationship with the participant and focusing on participant satisfaction, with the study staff taking a 
central role on this effort 
• 
Actively discuss with participants any questions and concerns pertaining to their newborn’s condition 
• 
Identifying potential problems and key retention factors, and developing intervention strategies regarding 
retention 
 
It is highly recommended that the ROR visit be conducted in-person. The research nurse/coordinator will contact the 
participants to schedule their ROR visit. 
1. The study site staff will phone the participant up to 2 times to offer times for the in-person ROR 
2. In case the participant is not reached by phone, the research coordinator will call the non-household contact 
3. In case the non-household contact is not reached by phone, the research coordinator will send the participant a 
certified letter (appendix 14) (includes family friendly WGS results letter). If the family has questions, the phone 
number to the HA genetic counselor assigned to the recruiting site will be provided. 
 
In the event, a study participant parent or caregiver participant does not return to the clinical trial site for an in-person 
return of results appointment, then: 
4. The study site staff will phone up to 2 times to offer results disclosure over the phone 
5. Call the non-household contact (see contact schedule above) 
6. Send a certified letter that includes the family-friendly WGS results letter, and have the Sanger results letter 
added to the medical record. The report is also available within Genome Gateway. 
 
3.d Informed Consent and HIPAA 
3.d.1 
Informed Consent (IC) Process 

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25 
 
One of the study research nurses/coordinators involved in the enrollment visit will carry out the process of IC. During the 
enrollment visit, the study participant (i.e. parent or caretaker of the infant who will have WGS testing) will review the ICF 
and then the research study coordinator obtaining consent will explain each section. During this process, individuals will 
be informed of all study aspects so that they can make an informed decision. Participants will then confirm their 
willingness to participate in the research study by signing the ICF. Consent of at least one parent/caregiver is required 
for the newborn to be enrolled and participate in the clinical trial, but both parents/caregivers are recommended if 
both are involved in care of proband. The participant will be given as much time as they need to read and ask questions 
about the ICF. The newborn’s parent or participant’s legally authorized representative will be informed that he/she is not 
obligated to participate in the study and that it is strictly voluntary. The individual or participant’s legal authorized 
representative will be informed that that he/she may withdraw from the study at any time and that withdrawal of 
consent will not affect his/her newborn’s subsequent medical treatment or relationship with the treating physician. 
• 
A frequently asked questions pamphlet (FAQ) has been provided to the study coordinators to help answer 
common patient questions. This is available in the Genome Gateway learning section as well as a hard 
copy/electronic file. This FAQ will be a live document and will continue to be modified as additional questions 
arise. This document is not IRB-approved and should not be given to participant families. 
The IC process will ensure that there is no penalty for not participating in a clinical trial and that treatment for the 
newborn will not be compromised if families choose to not participate, or if they cease participation at any time. By 
signing the ICF, the participant authorizes the use of their newborn’s PHI, indicates that they understand the study and its 
benefits and risks, and agrees to all other aspects of the study outlined in the form. 
 
A signed version of the ICF will be kept by the study staff in the study binder and on Genome Gateway. Copies of the 
signed ICF and W9 form will be uploaded to Genome Gateway. See section 3.f.2, section 1 for details on uploading 
documents to Genome Gateway. These documents will be added to the particular participant’s “files” section. 
 
The ICF contains or assures the following: 
• 
Disclosure of relevant information to participants about the research 
• 
The participant’s comprehension of the information 
• 
The participant’s voluntary agreement to participate in the clinical trial without coercion or undue influence 
• 
Disclosure of any appropriate alternative procedures and their risks and benefits 
• 
Disclosure of the extent of confidentiality that will be maintained 
• 
Statement of compensation and/or medical treatment available if injury occurs 
• 
Name, address, and telephone number of the participants 
 
During the study period, if there is a change in any of the study procedures that may affect the participant, the ICF will be 
revised and approved by the UAB IRB and then the supporting sites will be notified. Per NIH policy, the signed consent 
forms will be scanned into Genome Gateway and kept as part of the study record for at least 7 years after completion of 
the study and stored electronically in servers housed within the UAB School of Medicine and HudsonAlpha (sites will 
maintain all forms till completion of the study. After completion, all sites will send their paper materials to UAB for 
storage). Participants can withdraw their consent and revoke their data authorization at any time by informing the local 
study coordinator or investigator (if this occurs, please contact HudsonAlpha and Dr. Finnila). For participants that 
withdraw their consent, no further data will be collected via surveys and the recruitment site will be notified. If results 
have not yet been returned at the time of withdrawal, no results will be reported. In this case, the participant’s Genome 
Gateway account will be disabled, and the study team will be notified not to contact them. 
3.d.2 
Informed Consent Form 

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See appendix 3 for the informed consent forms (site-specific) 
3.e Study Intervention 
In this non-inferiority trial, we aim to compare technology-assisted community-based WGS result delivery by healthcare 
providers with formal genetic counseling by genetic counselors (GCs). The clinical trial will include parents/caretakers of 
newborns who undergo WGS. We estimate that 800 parents/caregivers will be enrolled into the clinical trial. Given the 
complexity of secondary findings and their implications, the parents of all children with secondary findings in the 
American College of Medical Genetics and Genomics (ACMG) gene list will be provided with formal genetic counseling 
(standard of care) and will thus be excluded from the clinical trial. We estimate that ~1.5% of sequenced probands will 
have such findings. Families enrolled before and after the trial period, (the trial is slated to end in January 2021, 
contingent on whether a no cost extension is to be awarded) will receive results from a GC. 
 
 
3.e.1 
Participant Randomization 
Randomization will occur centrally once the WGS results are available and clinical summaries of results are created, ~45- 
90 days after enrollment, using a computer-generated random number generator. The unit of randomization will be at 
the family level. Permuted block randomization with varying block size will be utilized. Randomization will be stratified by 
site and type of WGS result (positive/inconclusive/no finding). Participating families will be assigned to one of the two 
study arms in a 1:1 ratio. The randomization status of a participant family will be communicated to a site at the same 
time that the results and clinical summary/family-friendly report are provided to the site, and the site is notified that 
results are ready to be returned. The Randomization Binder will be kept by Kelly East, lead GC at HudsonAlpha, and will 
be communicated to the sites by uploading the result file within GG to the site coordinator and to the disclosing health 
care provider, if known. When files are uploaded, a note will be made of the randomization status. The randomization 
status of each case will also be documented and tracked in a secure, password-protected excel file outside of Genome 
Gateway, which will not be accessible to the rest of the study team. 
3.e.2 
Implementation of the Intervention 
Participants in both study arms will be provided with a similar set of resources and genetics learning topics (see section 
3.e.3 appendix 4 for resources and learning topics available on Genome Gateway) at the screening/enrollment visit to 
supplement in-person genetics consultation. Following randomization, parents will be scheduled for a WGS results 
delivery visit, 3 months (+/- 1 month) after enrollment by the research nurse/coordinator at each site. WGS result 
delivery visits will be coordinated when possible with a NICU follow-up appointment (if available at the site) to minimize 
additional visits and burden to the participants. In the case when an infant has yet to be discharged from the NICU, the 
study visit for the return of results and the assessments associated with this visit will occur in the hospital. In a case 
where the child dies prior to WGS result availability, or is no longer inpatient, an outpatient study visit with the parents 
should be scheduled for return of results. In rare instances where extenuating circumstances would prohibit a parent 
from attending an in-person return of results, results may be disclosed over the phone. Importantly, return of results over 
the phone should be limited to individuals who have extenuating circumstances prohibiting return to the hospital and not 
preferentially to those with certain WGS result types (e.g., negative). At the WGS results delivery visit, the clinician (either 
trained healthcare provider or GC, depending on the arm) will explain to parents the: 
1. Type of WGS result (positive/inconclusive/no finding) 
2. Level of diagnostic certainty of the result 
3. Recurrence risk, if known 

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4. Implications, if any, for family members 
5. Recommended next steps for follow-up and continued medical management in light of result (e.g. typical 
management guidelines for a certain condition, follow-up testing) 
6. Support resources available 
Genetic Counselor’s at HudsonAlpha will prepare and provide a family-friendly report of WGS results for both study arms 
(see appendix 1 for family –friendly report example). All families will be oriented to Genome Gateway and encouraged to 
review learning topics appropriate to their diagnostic findings, which will be assigned to them following result disclosure 
by a HudsonAlpha Genetics Counselor. 
Study investigators will audio record the return of results sessions, whether in-person or over the phone, so that GCs at 
HA can check for minor, major, and high-risk errors in communication of the WGS findings that will be corrected, 
appropriately. (see appendix 13 for the audio recording process) 
(1) Results (ROR) Recordings 
Prior to the WGS result disclosure participants will be reminded that the interaction will be recorded using a digital audio 
recorder, and their GG account username/password will be needed post-ROR for completion of the GCOS and FACToR 
measures. They will be reminded that the purpose of the recording is to help the study team understand how the results 
are described and what questions and topics come up during the discussion. Participants will be reminded that the 
recordings will only be used by the SouthSeq study and no identifiable information will be shared outside of the study 
team. 
Participants are given an opportunity to opt-out of the recording, but their results would have to be delivered by a GC. 
This can cause a delay if the participant is scheduled to have results delivered by a trained healthcare provider. 
Participants will not be given a copy of the recording. However, if they self-select to record the session on their own 
device that is permissible. 
The GC or physician conducting the results disclosure will begin by verbally introducing the people attending the return of 
results session. This introduction/preamble will be scripted (appendix 13), the audio recording is begun and the family ID 
is stated clearly on the recording, as well as the name of the clinician doing the disclosure. 
The parents/caregivers are counseled on the genetic test results, and when the interaction is finished, the recording is 
stopped. The digital recording file is uploaded in Genome Gateway to the designated HudsonAlpha GC (based on site) by 
the site study coordinator within 72 hours (3 business days) for positive or VUS results and within 7 business days for 
negative results. Errors will not be tracked within the GC arm, but only within the trained healthcare provider arm. Below 
are the HudsonAlpha GCs assigned to each clinical site: 
Birmingham, AL (UAB): Meagan Cochran, MS, CGC 
Jackson, MS (UMMC): Whitley Kelley, MS, CGC 
Baton Rouge, LA (BR): Veronica Greve, MS, CGC 
New Orleans, LA(LSU): Veronica Greve, MS, CGC 
University of Louisville (UL): Meagan Cochran, MS, CGC 
 
The GG platform is built to accept all types of files including audio files. The file should be named following this format 
SITE_PARTICIPANT ID.filetype (ex. UAB_00034.mp3). 

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Files from the GC (control arm) disclosures will be stored for future analysis. Files from the trained health care provider 
(experimental arm) will be reviewed by a HA genetic counselor for error tracking. At least one genetic counselor will 
review each disclosure. For the first 10 disclosures, the cases will be reviewed by all 4 HA genetic counselors (Kelly East, 
Whitley Kelley, Meagan Cochran, and Veronica Greve) to monitor for inter-rater consistency in error tracking. Typically, 
the HA genetic counselor designated to a site will be the individual doing the review/error tracking for all experimental 
arm disclosures at that site except for when she is not available and another team member will support this work. 
Errors will be tracked within GG utilizing a participant-specific questionnaire that is assigned to the GC completing the 
review. This questionnaire will ask about the length of the recording, the name of the clinician doing the disclosure, and 
whether any errors were noted as well as the contents of the error. The questionnaire will ask separately about each 
error type (safety error, major error, minor error). See section 3.g.1 and figure 2 for a breakdown of error types. 
3.e.3 
Intervention Materials 
(1) Educational Materials for the Parents/Caregivers on Genome Gateway 
Educational materials have been created for parents/caregivers to provide background information about the goals of 
SouthSeq study and about what to expect as a participant in the clinical trial. Materials also cover background 
information about genomics, the types of results that may be received through WGS, and the potential impact of those 
results. 
Educational content is provided to the parent in multiple formats including text, 2D graphics, videos, and animations. 
Content is provided as a series of small sections (i.e., learning topics). Effort has been taken to develop educational 
content that is understandable to participants who may have a low literacy level. 
The primary delivery mechanism for the educational content is the Genome Gateway web platform. Genome Gateway 
serves as the single source for participating families to review their designated learning topics. Participating families will 
be given an account and automatically assigned a series of brief learning topics at enrollment. HudsonAlpha genetic 
counselors will assign all additional learning topics (tailored based on results) manually after ROR at the same time that 
an electronic version of the result report and letter are uploaded to the participant’s files. The topics will vary on the type 
of WGS result returned but will be assigned in a consistent manner across all patients. Each site has been provided with 
two iPads for the participating families to use for enrollment and viewing of the educational materials. 
(2) Educational Materials/Training for the Healthcare Providers 
Educational materials for the healthcare providers that will be involved in disclosing WGS results will be in the form of 1) 
in-person training, 2) materials hosted in Genome Gateway for enduring/just-in-time access. 
A half-day in-person training will occur at each site prior to the launch of the clinical trial. Contents of this training will 
include background information and logistics about SouthSeq, WGS, Genome Gateway and the clinical trial. The majority 
of the training will focus on the delivery of WGS results. The training will consist of a few short didactic talks, hands on 
learning activities, small group discussion, and role-plays. Additional training sessions will be conducted remotely over 
the phone with a HudsonAlpha GC to allow providers to work through the training materials and care for patients, as well 
as onboarding of new study personnel when necessary. A provider should not return results until fully onboarded (e.g. 
trained with the protocol). 

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Fact sheets about each training topic have been developed as part of the training materials and are available for later 
reference (see appendix 6). All training materials will be organized and hosted within Genome Gateway and assigned to 
the healthcare providers for enduring access. 
Providers who will be disclosing results to participants as part of the clinical trial must attend the in-person training or 
participate in a “make-up” training, consisting of watching recordings of didactic portions of the training and a virtual 
workshop/conference call with a HudsonAlpha GC to cover the discussion, hands-on, and role-play portions of the 
training. 
The family-friendly report that will be developed for each case (by a HA genetic counselor) will also provide just-in-time 
education to the providers about a specific result and what it means – and provide a road map for topics to discuss with 
the participant. 
If providers have questions regarding the study and specific results, they will be instructed to reach out to a HudsonAlpha 
GC for assistance, rather than their own site-specific GC. This will allow for centralized tracking and management of 
questions and issues that come up across all the sites and limit compromises to the clinical trial. 
3.e.4 
Study Outcomes 
The primary hypothesis for this non-inferiority trial is that there will be no clinically relevant difference in parental 
empowerment, as a measure of health-related quality of life between parents in the Experimental (trained healthcare 
provider) arm when compared to the Standard of Care (genetics providers) arm. The primary study outcome is parental 
empowerment (McAllister et. al., 2011, PMID: 21255005), which will be measured at the WGS return of results (ROR) 
visit, ~3 months after enrollment (see appendix 7 for survey measures). To ensure completion of the primary outcome, 
parents or caregivers will be asked to complete the parental empowerment measure on-site (or over the phone) 
immediately after the return of results. The remaining measures included in the ROR visit will be available to complete via 
Genome Gateway at their convenience. 
The Secondary hypotheses will be that the active treatment arm (trained healthcare providers) will be non-inferior to the 
control arm (GCs) in terms of personal utility (Li et. al., 2017, manuscript in submission) and uncertainty (Bieseker et. al., 
2017, PMID: 27925165) (see appendix 7 for survey measures). In addition to assessing quantitative outcomes, we will 
also assess qualitative outcomes, including the diagnostic “journey” parents experienced during their child’s stay in the 
nursery or inpatient setting, the emotions they experienced while waiting for genomic results and upon receiving these 
results, parents’ reasons for wanting a genetic diagnosis, and whether those expectations were met. 
3.e.5 
Data Collection 
Data will come from all 4 clinical sites via self-administered surveys conducted online using Genome Gateway, or via 
paper surveys (scanned into Genome Gateway) in case of technical failure, lack of computer access or poor computer 
literacy. Organization of surveys and time points is indicated in Table 2 and Figure 1 (organized with most important 
measures located at beginning of survey). If parents do not respond to initial requests to complete follow-up surveys, 
they will be sent three automated reminder messages within two weeks of each study visit using the messaging feature 
of the Genome Gateway platform. (Genome Gateway is able to send reminders once the survey has been assigned by the 
research nurse or coordinator the reminder can be sent as a text/email/or message in Genome Gateway). 
1. The study site staff will phone the participant up to 2 times to offer times for the in-person ROR 
2. In case the participant is not reached by phone, the research coordinator will call the non-household contact 

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3. In case the non-household contact is not reached by phone, the research coordinator will send the participant a 
certified (includes family friendly WGS results letter). If the family has questions, the phone number to the HA 
genetic counselor assigned to the recruiting site will be provided. 
 
The use of these different data sources and modes for data collection provide some redundancy to assure that all 
outcomes are appropriately ascertained, creates a pragmatic approach for the study, and minimizes burden to the 
parents (relief from frequent contacts with the study team outside of scheduled follow-up visits). The data sources and 
approaches proposed are based on the considerable experience of the UAB clinical trial team and our collaborators in 
building comprehensive data capture platforms, collecting survey results, and linking to administrative data sources. 

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Table 2. Study Outcome Instruments, Key Covariates, and Measurement Times 
 
Instrument 
Timing of Assessment 
Enrollment 
ROR 
1 m 
post 
ROR* 
4 m 
post 
ROR* 
4m + 2 
wk post 
ROR 
Informed Consent Form (ICF) 
x 
Outcome of Sequencing 
x 
Sociodemographic 
Age, race/ethnicity, marital status, 
education, socioeconomic status, 
insurance status 
x 
x 
x 
x 
Empowerment 
GCOS† (McAllister et.al, 2011) 
x 
x** 
Worry/Positive Psychological Effects 
with Genetic Testing 
FACToR¢ 
x** 
x 
x 
Satisfaction 
Adapted from PACE (Patient Assessment 
of Communication Effectiveness) (Mazor 
et al., 2016) 
x 
x 
Knowledge 
GKA‖ (Schmidlen et. al., 2016) 
x 
Child’s Health 
VAS∞ 
x 
x 
x 
x 
Uncertainty 
PUGS‡ (Bieseker et. al., 2017) 
x 
x 
Personal Utility 
PrUΔ ( Li et. al., 2017) 
x 
x 
Medical Activation 
Medical Actions and non-Med/Patient- 
Initiated Actions Attributable to Genomic 
Testing 
x 
Healthy literacy 
Health Literacy Screening Questions 
(Chew et. al., 2004) 
x 
Numeracy 
SNS◊ (Fagerlin et. al., 2007), (Zikmund- 
Fisher et. al., 2007) 
x 
General Health 
Adapted from SF-12¿ (Ware et. al., 1996) 
x 
x 
x 
x 
Social support 
MOS¶ (Sherbourne et. al., 1991) 
x 
x 
x 
x 
Understanding 
Novel Measure 
x 
x 
x 
Family Communication 
x 
Information Seeking 
x 
x 
x 
ENR: Enrollment * Post WGS (whole genome sequencing); †Genetic Counseling Outcome Scale; ‡Parental Perceptions of Uncertainties in Genomic 
Sequencing; ¢The Feelings About genomic Testing Results #Genetic Counseling Satisfaction Scale; ‖Genetic Knowledge Assessment; ∞Visual Analog Scale Δ 
Parental Personal Utility Scale; ◊Subjective Numeracy Scale; §National Health and Nutrition Examination Survey;¿12-Item Short Form Survey; ¶Medical 
Outcomes Study. In green, primary analyses. ** GCOS and FACToR need to be completed in-person (or over the phone) immediately after ROR delivery 
before leaving session. 
 
 
(1) Primary Outcomes 
The main outcome to be assessed as part of this randomized controlled clinical trial will be parental empowerment as 
measured at the main time point for our study (i.e., immediately after the ROR visit). Parental empowerment will be 
measured using the validated Genome Counseling Outcome Scale (GCOS), which contains 24, 7-point Likert type items, 
with higher scores representing greater empowerment. The GCOS-24 that we are using for our participants measures 
patient reported outcomes (PRO) and has been proposed as a measure to evaluate routine clinical genetics services 
(McAllister et. al., 2011, PMID: 21255005). 

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(2) Secondary Outcomes 
To avoid survey fatigue and undue emotional burden, not all secondary or exploratory outcome instruments will be 
administered at each time point. The secondary outcomes assessed at the main time point (WGS ROR visit) for this study 
are: personal utility and parental uncertainty. Personal utility will be assessed using the parental personal utility scale 
(PrU). Parental uncertainty will be assessed using the Parental Perceptions of Uncertainties in Genomic Sequencing 
(PUGS). 
(3) Exploratory Outcomes 
Genetic knowledge and background genetic education will be addressed using the Genetic Knowledge Assessment 
(Schmidlen et. al., 2016, PMID: 26306685). The Genetic Knowledge Assessment (GKA) is a questionnaire containing 15 
true/false knowledge items and 4 education background questions. In addition, we will assess parental subjective 
understanding of their child’s results by asking respondents to rate their agreement. 
(4) Covariates 
Beyond the primary, secondary, and exploratory outcomes described above, a schedule of other data being collected for 
use in various analyses is provided in table 2. 
The FACToR measure needs to be completed, alongside GCOS, in-person (or over the phone) immediately after ROR 
delivery before leaving session. 
3.f Participant Evaluations and Follow-Up 
3.f.1 Timeline and Visit Schedule 
3.f.2 Scope 
(1) Screening/Enrollment Visit 
• 
Potential newborns (probands) will be identified via electronic medical record (EMR) review or referral from 
clinical care team 
• 
Research nurse/coordinator will complete screening log and will assign a screening ID (see section 3.c.3 above) 
o Will review inclusion and exclusion criteria in protocol 
o Will communicate with site genetics staff to help determine eligibility 
• 
May email physician or nurse practitioner caring for newborn to notify them that the family will be approached 
for study 
• 
It is important to note that WGS does not replace standard clinical genetic testing (e.g. microarray) 
• 
Research nurse approaches families for consent 
o Talk in-person in private area of the hospital (e.g. patient room, conference room) 
o Call or phone to arrange a meeting time for working and/or long distance families 
o Maintain contact for undecided families 
o Explain study procedures and mention secondary findings 
o After the consent form is signed (only parents/caregivers who have consented can participate in the 
clinical trial) blood specimens are collected from the proband and parents, if available 
o If both parents/caregivers express interest in participating, both parents/caregivers should be 
consented and complete their own surveys 

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• 
Families are supplied with an iPad (two will be ordered for your site for use in this study) to complete Genome 
Gateway registration, the enrollment/baseline survey, and family history questionnaire/pedigree in Genome 
Gateway at enrollment. 
o The research nurse will not assist the parents/caregivers as much as possible with answering 
questions on the enrollment survey unless a technical issue arises. 
 
 
Detailed instructions regarding Genome Gateway participant registration and 
navigation are below: 
 
 

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• 
After logging-in to Genome Gateway, you will need to create a new patient account 
 
 
 

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Notes for research nurse/coordinator: 
• 
Each participant will need to be enrolled into a study site by selecting from the site list when filling out the 
patient enrollment 
• 
Each participant will need to be associated with a primary provider (varies by site -physician currently overseeing 
care for proband). Can be selected when filling out patient information 
• 
Study IDs will be automatically assigned to participants once a Genome Gateway account is created 
o Don’t forget to add study ID to the screening log 
• 
The study IDs will be visible under participants’ names on any screen with that information 
• 
The study ID number will also be printed on the blood sample tube labels 

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Patient Questionnaires 
 
 

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• 
Research nurse will complete assigned surveys in Genome Gateway. 
o These surveys are focused on phenotypes, previous genetic testing, prenatal testing (if known) 
and the enrollment process. (see screenshot steps below) 
o This information will be accessible to the analysis team at HudsonAlpha. 
 

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o The due date should be up to ROR (roughly 2 ½ months for baseline). All subsequent surveys will 
be set 1-month from the day you assign the survey. 
o The due date reminders will be automatically preselected for you (2-day before, 7-days before, 
and 14-days before) 
• 
Research nurse will ship samples to the Clinical Services Laboratory at HudsonAlpha and submit them for 
sequencing via online portal. 
• 
The research nurse will upload the W9 (needed for payment) and the informed consent form to GG. 
o Screenshots highlighting how to upload documents are below. 

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Uploading Documents to Genome Gateway 
 
 
 

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• 
Forms/survey measures completed at enrollment 
o Informed Consent Form (ICF)- (paper form uploaded to Genome Gateway; hard copy kept in 
study binder) 
o W9 form (paper form uploaded to GG; hard copy kept in study binder until clinical trial team 
informs the coordinator to destroy- 7 years) 
o Participant Enrollment Survey 
o Sociodemographic in GG 
o Genetic Counseling Outcome Scale (GCOS) 
o Genetic Knowledge Assessment (GKA) 
o Visual Analog Scale (VAS)- Child’s Health 
o Parental Perceptions of Uncertainties in Genomic Sequencing (PUGS) 
o Health Literacy 
o Subjective Numeracy Scale (SNS) 
o 12-item Short Form Survey (SF-12) 
o Medical Outcomes Survey (MOS) 
o Research Nurse/Coordinator Surveys (phenotype, other genetic testing, enrollment notes, etc.) 
If a parent/caretaker participant doesn’t respond to the baseline measures, the clinical trial team will contact the study 
coordinator, to remind the participant to complete surveys via GG and/or over the phone, after a biweekly data pull is 
completed to generate a list of non-completers. All data collected pre-ROR, will still be valid as baseline data. 
 
 
(2) Return of Results (ROR) Visit 

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• 
After samples are sequenced, analyzed, and variants of interest have been Sanger validated (by HudsonAlpha, 
PerkinElmer, EGL, etc.), the HudsonAlpha analysis team will contact the clinical team and hold a variant review 
meeting (VRC) to discuss any findings. 
• 
After VRC, the enrolled families will be scheduled for a return of results (ROR) appointment by the site research 
nurse/coordinator (preferably in-person) where a GC/healthcare provider will return the finding(s) 
o The ROR can be completed over the phone if necessary, as a last resort. Reasons for offering a phone 
ROR include families who are unwilling to return to clinic because of distance or psychosocial 
distress. Caution should be made to not let the type of result dictate the ROR setting (i.e. do not 
preferentially offer negative results phone disclosures and positive results in-person consultations). 
o If a phone ROR is to be completed, the same provider should do the disclosure who would have been 
expected to do an in-person meeting. The phone experience should be made to feel as similar to the 
in-person experience as possible (length, content, staff, flow). 
o It is important that the parent/caregiver who completes the enrollment surveys continue to be the 
person attending and completing the ROR visit and surveys (In-clinic survey and At-home survey). 
• 
The research nurse will place the clinical Sanger report along with the family-friendly genetic counseling letter in 
the child's medical record so that clinicians will have access to the finding(s). 
• 
The (GCOS/FACToR) ROR questionnaire is administered by the research nurse immediately following the ROR 
visit. After completion of the ROR visit, the 1-month post ROR, and 4-month post ROR post-enrollment can be 
programmed for automatic administration. 
o If completed over the phone, the answers need to be recorded on paper, and uploaded to 
Genome Gateway 
• 
Forms/survey measures completed at ROR visit 
o Sociodemographic 
o Genetic Counseling Outcome Scale (GCOS) 
 
This survey needs to be administered by the research nurse/coordinator after ROR. 
This is the primary outcome and needs to be completed directly after ROR. 
o The Feelings About genomic Testing Results (FACToR) 
 
This survey needs to be administered by the research nurse/coordinator after ROR. 
This needs to be completed directly after ROR because it is an important covariate. 
o Patient Assessment of Communication (Adapted from PACE) (Mazor et. al., 2016) 
o Visual Analog Scale (VAS)- Child’s Health 
o Parental Perceptions of Uncertainties in Genomic Sequencing (PUGS) 
o Parental Personal Utility Scale (PrU) 
o 12-item Short Form Survey (SF-12) 
o Medical Outcomes Survey (MOS) 
o Understanding (Novel Measure) 
• 
The research nurse/coordinator in partnership with HudsonAlpha will determine who the most 
appropriate clinical provider at each site is to receive the harmonized “provider survey.” This provider 
should be the physician likely to make a clinical decision based on the WGS results at the time of ROR. If 
the neonate is inpatient this physician will likely be a neonatologist providing medical care for the 
neonate, if already discharged it could be pediatrician or another specialist depending on the neonate’s 
symptoms. The site coordinator will determine the status of the proband (inpatient/outpatient) at the 
time of ROR (consulting with the family about this issue if already discharged) and will send the provider’s 
name and contact information to Kyle Brothers, MD, PhD (kyle.brothers@louisville.edu) within a week of 

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ROR appointment. Information can be sent via the Genome Gateway messaging tool. Information to be 
sent includes: 
o Study ID 
o Result type (positive/inconclusive/no finding) 
o ROR date 
o Clinical provider’s name 
o Clinical provider’s contact information (email (required), phone, address) 
 
(3) 1-month post-ROR Visit 
• 
Forms/survey measures completed at 1-month post-ROR visit 
o Sociodemographic (if status has changed) 
o The Feelings About Genomic Testing Results (FACToR) 
o Patient Assessment of Communication (Adapted from PACE) 
o Visual Analog Scale (VAS)-Child’s Health 
o 12-item Short Form Survey (SF-12) 
o Medical Outcomes Survey (MOS) 
o Understanding (Novel Measure) 
o Information Seeking 
 
(4) 4-month post-ROR Visit 
• 
Forms/survey measures completed at 4-month post-ROR visit 
o Sociodemographic (if status has changed) 
o The Feelings About Genomic Testing Results (FACToR) 
o Patient Assessment of Communication (Adapted from PACE) 
o Visual Analog Scale (VAS)- Child’s Health 
o Parental Personal Utility Scale (PrU) 
o 12-item Short Form Survey (SF-12) 
o Medical Outcomes Survey (MOS) 
o Understanding (Novel Measure) 
o Information Seeking 
 
(5) 4-month plus 2 weeks post-ROR Visit 
• 
Forms/survey measures to be completed at 4-month plus 2 weeks post-ROR visit 
o Family Communication 
o 
Medical Actions and non-Med/Patient-Initiated Actions Attributable to Genomic Testing 
 
3.f.3 Follow-Up of Participants during the Study 
Participants will be actively followed through all study visits until completion of the study. This includes, but is not limited 
to: 

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• 
Genome Gateway can provide email and text reminders (if participant provided a cell phone number and 
consented to text reminders) to users for the purpose of notifications of due dates, new messages, new file 
uploads, new learning assignments, and new questionnaires. 
• 
Research Nurses/coordinators will confirm contact information and remind the participants that they will be paid 
for follow-up surveys 
• 
A generic mailing will be sent to participants to keep them engaged and informed of their participation ** 
pending IRB approval** 
Upon onboarding of Genome Gateway, by default, all participants will receive text and email notifications from GG when 
any new assignment, questionnaire, files, or message is sent. The participants will have the option to decline email/text 
notifications during the onboarding process. They may also decline email/text notifications during the course of the trial, 
if the alerts become burdensome. When a provider or administrator assigns learning articles and questionnaires, a due 
date for those items must be set (the deadline for questionnaires is 1 month). If a due date is set for the completion of 
those, a set of reminders can be added which will cause an automatic email/text notification to be sent at a designated 
number of days before the due date. For example, it is possible to set a due date of January 12 with reminders to be sent 
2, 7, and 14 days prior to the due date. This is done at the time of assignment. 
3.g Safety Reporting 
3.g.1 
Errors in Reporting of Results 
Errors will be tracked within GG utilizing a participant-specific questionnaire that is assigned to the GC completing the 
review. This questionnaire will ask about the length of the recording, the name of the clinician doing the disclosure, and 
whether any errors were noted as well as the contents of the error. The questionnaire will ask separately about each 
error type (safety error, major error, minor error). See Figure 2 for a breakdown of error types. 
Figure 2. Types of Genetic Test Reporting Errors 
 
 
 
 
Minor Errors 

Version 1.0; 02/18/2019 
46 
 
In the case of a minor error, these errors will be tracked internally but no intervention will be made. 
Definition: Errors in the non-critical details that have little expected impact on participant understanding, decision-making 
and management. 
Examples: 
● Saying the participant “has the gene” instead of saying the participant “has a gene mutation” 
● Saying the gene is on the incorrect chromosome 
● Terminology misuse - heterozygous versus homozygous 
 
Major Errors 
In the case of a major error, the disclosing healthcare provider will receive a message from the reviewing GC clarifying the 
error and recommending he/she follow-up with the participant to convey corrected/additional information. The clinician 
is expected to correct the misconception both with the patient and any documentation they did clinically at their site. If 
the clinician asks for assistance or does not feel comfortable addressing the error, the genetic counselor will be 
responsive to those requests. If a participant reaches out to HA with questions, Kelly East will address concerns, but the 
disclosing healthcare provider is expected to be the one to have direct patient contact and a patient relationship. 
Definition: Errors in the critical content that have a significant expected impact on participant understanding, decision- 
making, and/or management. 
Examples: 
● Wrong recurrence risk (i.e. stating recurrence risk is 25% when it is actually <1%) 
● Confusion regarding etiology (de novo, parental carrier status) 
● False reassurance (i.e. counseling that WGS will provide a concrete answer as to participant’s life expectancy) 
○ 
Negative results and the misconception that it rules out genetic etiology (explicit statements) 
● Misunderstanding of pathogenicity/penetrance 
○ 
Likelihood of actual development of features/severity 
● Incorrect understanding of a VUS (saying it is highly unlikely to be the cause/is nothing to worry about; or saying 
it is definitely the cause) 
 
High-risk Safety Errors 
In the case of a high-risk safety error, this will be brought to the attention of the clinical trial leadership team and the 
Data Safety Monitoring Board (DSMB) for recommendations on how to manage the situation. 
Definition: Errors that have a high risk of immediate and detrimental impact on participant safety; should be reported to 
DSMB. 
Examples: 
● Recommendation of invasive testing or procedure based on a misinterpreted test result 
● Giving back wrong result; counseling the wrong family 
● Failure to report a high impact incidental finding 

Version 1.0; 02/18/2019 
47 
 
3.h Data and Safety Monitoring Board (DSMB) Activities 
We will convene a DSMB for additional monitoring of study procedures. The safety of the study participants is the highest 
priority for this project. The ability to make appropriate, sound scientific decisions regarding the outcome of each 
participant, as early as possible, is the top priority. The DSMB will be comprised of three scientists/clinicians who are 
independent of the study. All safety monitoring body member(s) will complete and sign the Conflict of Interest (COI) 
Statement. Elizabeth Rahn, PhD (Clinical Trial/Scientist) will provide and track the COI statements prior to providing 
DSMB members study materials and then track this on an annual basis. See appendix 8 for additional information. 
3.h.1 
DSMB Responsibilities 
• 
Review the outcome instruments, informed consent documents and plans for data safety and monitoring 
• 
Evaluate the progress of the clinical trial, including periodic assessments of data quality and timeliness, 
recruitment, accrual and retention, participant risk versus benefit, and other factors that can affect study 
outcome 
• 
Consider factors external to the study when relevant information becomes available, such as scientific or 
therapeutic developments that may have an impact on the safety of the participants or the ethics of the trial 
• 
Review study performance, make recommendations and assist in the resolution of problems reported by the 
Principal Investigator(s) (Clinical Trial PIs) 
• 
Protect the safety of the study participants and monitor the rate and scope of errors reported in the 
experimental arm of the clinical trial. 
• 
Report on the safety and progress of the trial 
• 
Make recommendations to the PIs concerning continuation, termination or other modifications of the trial based 
on the observed beneficial or adverse effects of the intervention under study 
• 
The PIs will report findings of the DSMB to NGHRI in accordance with reporting guidelines 
• 
Ensure the confidentiality of the study data and the results of monitoring 
• 
Assist in commenting on any problems with study conduct, enrollment, sample size, and/or data collection. 
 
The DSMB will discharge itself from its duties when the last participant completes the clinical trial. 
 
3.h.2 
DSMB Board Process 
At the initial meeting the DSMB will discuss the protocol, suggest modifications, and establish guidelines to study 
monitoring by the Board. The DSMB Chairperson, in consultation with the Principal Investigator and the study team, will 
prepare the agenda to address the review of provider education materials, modifications to the study protocol and 
informed consent document, initiation of the trial, reporting of return of results errors, and statistical analysis plan. 
Meetings of the DSMB will be held annually or more frequently at the discretion of the DSMB, if necessary. The study 
investigators or their designees will attend the meetings. An emergency meeting of the DSMB may be called at any time 
by the Chairperson or by the PIs should safety questions or other unanticipated problems arise. The meetings are closed 
to the public because discussions may address confidential participant data. The meetings are attended by the Principal 
Investigators and members of their staff. Meetings may be convened as conference calls, as well as in-person. 
3.h.3 
DSMB Meeting Format 

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48 
 
DSMB meetings will consist of open and closed sessions. Discussion held in all sessions is confidential. The PI and key 
members of the study team attend the open sessions. Discussion will focus on the conduct and progress of the study, 
including participant accrual, protocol compliance, and problems encountered. 
 
Each meeting must include a recommendation to continue or to terminate the study and whether the DSMB has any 
concerns about participant safety made by a formal DSMB majority or unanimous vote. Should the DSMB decide to issue 
a termination recommendation, the full vote of the DSMB is required. In the event of a split vote, majority vote will rule 
and a minority report will be appended. The DSMB Chair provides the tiebreaking vote in the event of a 50-50 split vote. 
A recommendation to terminate the study may be made by the DSMB at any time by majority vote. The Chair should 
provide such a recommendation to the PIs immediately by telephone and email. 
 
3.h.4 
Meeting Materials 
A DSMB interim report template will be prepared by the study staff, typically by the study statistician, and will be 
reviewed by the DSMB members at the first meeting. The format and the content of the reports for, and the plans for, 
interim analyses will be finalized and approved at the initial DSMB meeting, although changes throughout the trial may 
be requested by the Board. The reports will list and summarize safety data and describe the status of the study. All 
meeting materials will be sent to PIs who will forward the materials to the DSMB between 7 to 14 days prior to the 
meeting. The reports will be numbered and provided in sealed envelopes and can be returned within an express mailing 
package or by secure email, as the DSMB prefers. In select cases, PIs may approve direct mailing of the reports from the 
study to the DSMB. 
 
3.h.5 
DSMB Reports 
Reports generally include administrative reports by site that describe participants screened, enrolled, completed, and 
discontinued, as well as baseline characteristics of the study population, and interim error statistics from HudsonAlpha 
obtained through review of the ROR sessions (i.e. errors tracking). Other general information on study status may also be 
presented. The DSMB may direct additions and other modifications to the reports on a one-time or continuing basis. The 
reports may also contain data on study outcomes, including safety data, and perhaps efficacy data. 
 
A formal report containing the recommendations for continuation of, or modification to the study will be prepared by the 
DSMB Chairperson, PIs, or designee. The draft report will be sent to the DSMB members for review and approval. It is the 
responsibility of the PIs to distribute the DSMB recommendation to all co-investigators and to ensure that copies are 
submitted to the IRBs. As previously stated, the formal DSMB report must include a recommendation to continue or to 
terminate the study. This recommendation should be made by formal majority vote. A termination recommendation may 
be made by the DSMB at any time by majority vote. In the event of a split vote in favor of continuation, a minority report 
will be contained within the regular DSMB report. See Data Safety Monitoring Plan appendix 9 for additional information. 
 
3.h.6 
DSMB Confidentiality 
All materials, discussions and proceedings of the DSMB are completely confidential. Members and other participants in 
DSMB meetings are expected to maintain confidentiality. 
3.i Study Compliance 
Investigators will conduct the study in an efficient and diligent manner and in conformity with this protocol; generally 
accepted standards of GCP; and all applicable federal, state, and local laws, rules and regulations relating to the conduct 
of the clinical study. The clinical trial PI also will allow audits, IRB/Independent Ethics Committee review and regulatory 

Version 1.0; 02/18/2019 
49 
 
agency inspection (if required) of trial-related documents and procedures and provide for direct access to all study- 
related source data and documents. The investigators will prepare and maintain complete and accurate study 
documentation in compliance with GCP standards and applicable federal, state, and local laws, rules and regulations. 
Study documentation will be promptly and fully disclosed by the clinical trial PI upon request for inspection, copying, 
review, and audit at reasonable times by any regulatory agencies. The investigators will promptly take any reasonable 
steps that are requested by designated representatives as a result of an audit to cure deficiencies in the study 
documentation and GG surveys. Persons debarred from conducting or working on clinical studies by any court or 
regulatory agency will NOT be allowed to conduct or work on this study. 
 
3.j Data Collection and Outcome Instruments 
All data for this study will be collected by study staff in accordance with 21 CFR Part 11 rules and will meet all regulatory 
requirements. All data entry will use the Genome Gateway platform, with which our team has extensive experience. All 
outcome instruments will be completed electronically in the Genome Gateway platform by the participants or research 
nurse/study coordinator(s). Beyond the informed consent, participants will complete no paper surveys, unless there is a 
technical issue with the Genome Gateway platform, or a family cannot complete the survey measures online (paper 
copies will be used and scanned into Genome Gateway). All Genome Gateway forms filled out by participants or study 
personnel will be considered source documents and must be maintained in a study binder. 
 
3.j.1 Source Documentation 
All Genome Gateway forms filled out by participants or study personnel will be considered source documents and kept 
electronically. All electronic forms and logs in Genome Gateway platform are encrypted and password protected and 
hard copies can be printed if required. A detailed listing of all current study forms is below in Table 3. 
 
Table 3. Study Forms 
 
Form 
Visit Administered 
Instructions 
Location 
Informed Consent 
Enrollment Visit 
Participant/s reads consent. Study staff 
obtaining consent should sign, date, and time 
stamp 
Paper, uploaded to 
Genome Gateway 
Screening/Decliner 
Survey 
Enrollment Visit 
Completed by research nurse or study 
coordinator 
Electronic Copy 
Enrollment Survey 
Enrollment Visit 
Completed by parent or caregiver after study 
enrollment 
Genome Gateway 
Return of Results 
(ROR) Survey (In- 
clinic and At-home 
surveys) 
GCOS and FACToR at 
ROR Visit; Additional 
measures after visit 
Complete primary outcome measure (GCOS) 
and FACToR measure immediately after ROR, 
additional measures can be completed at 
participant’s convenience 
Genome Gateway 
1-month post-ROR 
Survey 
Complete 1-month 
post ROR 
Complete survey online using GG 
Genome Gateway 
4-month post-ROR 
Survey 
Complete 4-months 
post ROR 
Complete survey online using GG 
Genome Gateway 
4-month plus 2 
weeks post-ROR 
Survey 
Complete 4-months 
plus 2 weeks post- 
ROR 
Complete survey online using GG 
Genome Gateway 

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50 
 
User roles (researchers, providers, patients/participants and administrators) with secure log-in will be defined. The 
following information will be tracked: current user, database accessed, date, and time and the application will be stopped 
automatically after 15 minutes of user inactivity requiring a fresh log-in. All data will be collected via the questionnaires in 
Genome Gateway. The clinical trial study coordinator, clinical trial project manager and statistician will review all data 
collected weekly. This will help ensure all electronic forms are being completed correctly, are intact, and have been 
entered into system correctly. 
3.j.2 General Instructions for Completing Forms 
All data recorded in Genome Gateway will be maintained according to the International Council for Harmonization of 
Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines. Instructions for 
completing the questionnaires to ensure quality and consistency in data collection are below. 
3.j.3 Retention of Study Documentation 
Investigators will adhere to rigorous requirements and will retain copies of all paper (e.g. informed consent), electronic 
forms, and all other study documents for a period of no less than 7 years. Each site will maintain all documents, and at 
the close of the study UAB will retain all site documents. 
3.j.4 Administrative Forms 
Table 4. Administrative Forms 
 
Form 
Description 
Location 
Study Roster 
Complete study personnel roster and 
signature of all members of the study 
team. It is the responsibility of the 
Principal Investigators and/or Clinical 
Project Manager to: designate 
individuals approved to make form 
entries and changes, and note the 
date when any study team member is 
removed from the team for any 
reason. 
Study Binder; Table 1, section 3.b 
Schedule of Visits and Evaluations 
Listing of all schedule study visits and 
evaluations 
Study Binder; Table 2, section 3.f.1 
Training Log 
Record of trained study personnel 
Study Binder 
Appendix 10 
Screening Log 
Log of individuals screened and 
enrolled 
Study Binder 
Appendix 11 
Project Team Communication Log 
Record of official study calls/emails 
between study staff 
Study Binder 
Appendix 12 
 
3.k Data Management 
HudsonAlpha has extensive experience in data management, currently managing several studies. HudsonAlpha has 
developed the Genome Gateway platform that serves as a shared platform to seamlessly support data management 

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needs across the spectrum of this project. Genome Gateway is hosted on and data in is stored on a secure, HIPAA cloud- 
based platform offered through Datica, Inc. Data from SouthSeq participants used by researchers and genome analysts is 
coded and de-identified prior to being made available to those individuals. De-identified data is stored on a secure File 
Transfer Protocol (FTP) server hosted by HudsonAlpha and can be tracked via a unique study ID number generated for 
each participant. Genome Gateway is the center of data management for SouthSeq across all sites involved in the study. 
 
 
3.l Reports 
Reports will be prepared by the project manager, Dr. Finnila to keep the study staff up to date and engaged, as well as 
help to check quality control. These reports will take the form of: 
• 
Bi-weekly status emails to the PI 
o Number of enrollees 
o Status of any non-compliance (Number of participants who haven’t completed the required surveys) 
o Rate of WGS results (how long it takes for WGS results to be generated) 
o Any site-identified problems or concerns 
• 
Bi-weekly emails to Clinical Trials Team 
o Number of enrollees 
o Status of any non-compliance (Number of participants who haven’t completed the required surveys) 
o Rate of WGS results (how long it takes for WGS results to be generated) 
o List of completers for payment 
o Any site-identified problems or concerns 
• 
Enrollment and data and safety monitoring reports prepared by study personnel to be reported to the DSMB, 
NGHRI, and the IRB as requested. 
• 
Bi-weekly reports that will be compiled by the program manager in presentation form for the clinical trial 
meetings will include 
o Target and actual enrollment, 
o Enrollment status (screened, declined, active, completed, and lost to follow-up). 
o Individuals who have a Provider Genome Gateway account type can see if a participant has 
completed a survey 
o Electronic forms completed and entered 
Reports will start at month 2 of the clinical trial. 
3.m 
Study Completion and Closeout Procedures 
At the conclusion of the study, the following procedures will be done to verify all study-related obligations have been 
met. Verification that all study procedures have been completed include, but are not limited to the following procedures 
include: 
• 
All data has been collected 
• 
All data queries have been completed 
• 
All electronic source materials have been properly documented and archived 
• 
Assurance that correspondence and study files are accessible for audits 
• 
Reminder to investigators of their ongoing responsibility to maintain study records and to report any relevant 
study information to NGHRI. 
• 
IRB notification of the study completion and stored copy of the notification. 

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52 
 
• 
Preparation of a report summarizing the study’s conduct and results. 
• 
Participant notification of the study completion. 
 
3.n Policies 
All staff will be instructed in their study-specific responsibilities regarding data safety and confidentiality. Additionally all 
staff will be cautioned against the release of data to any unauthorized individuals and no data will be released to any 
individual without first obtaining approval from NGHRI and/or the IRBs. 
 
This section of the MOOP will discuss the safeguards that have been put in place by the PIs to ensure participant 
confidentiality and data security. 
 
The following is a list of study participant confidentiality safeguards: 
• 
Data flow procedures – HudsonAlpha will provide thorough data entry and confidentiality training to all staff 
involved in data collection and data entry. 
• 
Electronic files – All data identifying participants is kept as part of Genome Gateway and is hosted on a 
HIPAA-compliant server that uses both physical security as well as data encryption to secure data. 
• 
Data listings – No personally identifying data will be included in any published item (paper, database, etc.). 
The only place personally identifiable data is stored is within Genome Gateway. That data is only accessible to 
provider and administrator level users at the study sites. 
• 
Data distribution – Data listings containing names and other PHI are never distributed. Data access is 
controlled through Genome Gateway accounts. Only providers and administrators have access to PHI through 
Genome Gateway. Every assurance to keep those accounts to a minimum is being made. 
• 
Data disposal – Computer listings that contain participant-identifying information will be disposed of in an 
appropriate manner. 
• 
Access – Access to participant records in Genome Gateway is tightly controlled. Each research site has its own 
‘program’ within Genome Gateway allowing it to operate semi-autonomously from the other sites with 
regards to participant data. Provider accounts can be associated with a program providing that user with 
participant data that is limited only to those participants enrolled at that site. Any individual requesting a 
Genome Gateway account outside of a participant being enrolled in the study must have an administrator 
level user create the account. The limited number of administrator accounts associated with SouthSeq keep 
this capability limited to 5 individuals at HudsonAlpha involved in the study that are all certified to access PHI. 
• 
Storage – All data will be stored on either HudsonAlpha servers or by Datica, Inc., the HIPAA compliant 
hosting platform used by Genome Gateway. 
• 
Passwords – Accessing Genome Gateway requires both a unique username and password that must be at 
least 8 characters in length, contain at least one capital letter, one number and one special character. There 
is no general access to Genome Gateway allowed for the SouthSeq instance of the platform. Additionally, all 
users can have specific permissions added or removed based on need. 
• 
User Training – All staff at sites using Genome Gateway will have training on using the Genome Gateway 
platform that includes an emphasis on system security and on how participant data stored in Genome 
Gateway should be accessed, used and shared. 
• 
System Testing – All changes, updates, and new programs within Genome Gateway undergo multiple rounds 
of testing prior to deployment. A separate staging instance that mirrors the functionality of, but contains no 
data related to, the SouthSeq instance has been created for this purpose. Once testing has been conducted 
and verified on the staging instance, the deployment to the SouthSeq instance is also tested to ensure that 
functionality and performance is operational as expected. This includes an assurance that the username and 
password access still functions as expected. 

Version 1.0; 02/18/2019 
53 
 
• 
System Backups – Data is automatically backed up by Datica, Inc. as part of the hosting and storage service. 
Genome Gateway is hosted by Datica, Inc. and uses a cloud-based computer strategy to have multiple, 
redundant backup systems in place. Non-PHI data is backed up and stored each night on a separate, secure 
FTP site hosted by HudsonAlpha Institute for Biotechnology. 
 
3.n.1 
Confidentiality Procedures 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be transmitted to 
and stored in the UAB Department of Biostatistics in the School of Public Health, directed by Dr. David Redden (Co- 
Investigator). This will not include the participant’s contact or identifying information. Rather, individual participants and 
their research data will be identified by a unique study identification number. The study data entry and study 
management systems used by clinical sites and by research staff will be secured and password protected. At the end of 
the study, all survey data will be de-identified and archived at UAB. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use during the study. 
At the end of the study, all records will continue to be kept in a secure location for as long a period as dictated by the 
reviewing IRB, Institutional policies, or NGHRI requirements. 
 
3.n.2 
Publications 
National Institutes of Health (NIH) Public Access Policy ensures that the public has access to the published results of NIH 
funded research. It requires scientists to submit final peer-reviewed journal manuscripts that arise from NIH funds to the 
digital archive PubMed Central upon acceptance for publication. 
 
Publication will be based on data from HudsonAlpha, UAB, UMMC, Children’s Hospital of New Orleans and Woman’s 
Hospital (Baton Rouge) that has been analyzed as stipulated in the statistical analysis plan. Investigators will not present 
data gathered from one site before the full publication, unless formally agreed to by all Investigators. Upon completion of 
the study we will publish our findings in peer-reviewed journals. Authors must participate in the writing of the paper in 
accordance with the International Committee of Medical Journal Editors guidelines (N Engl J Med 1991). First authors are 
expected to delete names from the final list of authors if those individuals have not satisfied criteria for authorship in 
accordance with those guidelines. In general, the researcher who first conceived of the project and submitted a plan for 
the manuscript should have the option of serving as first author. Conflicts in first authorship will be resolved by the study 
team PIs. In addition to SouthSeq publications, study team members will be involved in Phase II of the Clinical Sequencing 
Evidence-Generating Research (CSER2)-wide consortium projects and publications. 
 
The SouthSeq study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical 
Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, this trial will be 
registered at ClinicalTrials.gov, dbGap, and results information from this trial will be submitted to ClinicalTrials.gov. 
 
3.o MOOP Maintenance 
The MOOP will be maintained and updated throughout the study by the clinical trial study staff at UAB, as necessary. The 
most current copies of the MOOP will be kept on Freedcamp platform (www.freedcamp.com), and a hard copy, in loose- 
leaf form, will be kept in staff issued binders along with other study files for staff reference. Each page of the MOOP is 
numbered, dated, and contains the version number to eliminate any confusion. As a living document the MOOP will be 
continuously reviewed by study staff to ensure the operating procedures described are accurate. If any procedures are 

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54 
 
changed or modified, the MOOP will be updated and the new version will be emailed and printed (by each site) for study 
binders for all study staff members. 
 
4. BIBLIOGRAPHY 
Bieseker et. al., 2017, PMID: 27925165 
Chew et. al., 2004, PMID: 15343421 
Fagerlin et. al., 2007, PMID: 17641137 
Li et. al., 2017, manuscript in submission 
Mazor et. al., 2016, PMID: 26979476 
McAllister et. al., 2011, PMID: 21255005 
Richards et. al., 2015, PMID: 25741868 
Schmidlen et. al., 2016, PMID: 26306685 
Sherbourne et. al., 1991, PMID: 2035047 
Ware et. al., 1996, PMID: 86228042 
Zikmund-Fisher et. al., 2007, PMID: 17652180 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 1: WGS Results Report (Family-Friendly) 

Page 1 of 2 
 
 
 
Participant Name: 
Participant ID#: 
Participant DOB: 
Report Date: 
This letter describes genetic test results from the SouthSeq research study (research protocol No. 
300000328). 
Your child was enrolled because he or she was in the neonatal intensive care unit (NICU) and 
had symptoms that may be due to a genetic problem. 
Reason for testing: Based on information provided to the research lab, the child has a history of 
[symptoms]. 
 
Results related to the reason for testing (also called primary results): 
No genetic changes reported (also called a negative result) 
Result 
• 
The whole genome sequencing test was not able to find a genetic cause for your child’s symptoms. 
• 
It is still possible that your child’s symptoms have a genetic cause. Current tests cannot find or 
understand all of the genetic changes that may cause health problems. 
Future care 
• 
No test is perfect. Genetic testing will continue to change and improve over time, as will the 
knowledge of how genetic changes can cause health problems. 
• 
Other genetic tests may be needed for your child based on [his/her] personal and family medical 
histories. Please continue follow-up with your child’s healthcare providers to learn about new 
information, testing options, or research studies. 
 
Results NOT related to the reason for testing (also called secondary results): 
No other genetic changes reported (also called a negative result). 
Keep in mind: 
• 
In addition to looking for the reason for your child’s symptoms, this test looked at 59 other genes* 
that can cause disease in the future. 
• 
The whole genome sequencing test did not find any specific genetic changes associated with risk 
of developing a disease in the future. 
• 
This does not mean your child will not develop a genetic disease in the future. Humans have more 
than 20,000 genes. There are many gene changes that may cause disease that the lab cannot find 
or understand. 
If you have questions, please contact your child’s healthcare team at the NICU where [he/she] 
was enrolled. 
You may also contact a study genetic counselor at the information below. 
Kelly East, MS, CGC 
Certified Genetic Counselor 
HudsonAlpha Institute for Biotechnology 
256-327-0461 

Page 2 of 2 
 
 
 
 
Participant Name: 
Participant ID#: 
Participant DOB: 
Report Date: 
 
Information about the test 
Keep this information for future use 
 
Whole genome sequencing was done on a research basis at the HudsonAlpha Institute for Biotechnology 
(not in a CAP/CLIA environment). Sequencing was done on an Illumina HiSeq X sequencer at an 
approximate depth of 30X. Variant pathogenicity was determined using ACMG criteria. 
 
*Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 
update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. 
Genet Med. 2017. https://www.nature.com/articles/gim2016190 

Page 1 of 2 
 
 
 
 
Participant Name: 
Participant ID#: 
Participant DOB: 
Report Date: 
This letter describes genetic test results from the SouthSeq research study (research protocol No. 
300000328). 
Your child was enrolled because he or she was in the neonatal intensive care unit (NICU) and 
had symptoms that may be due to a genetic problem. 
Reason for testing: Based on information provided to the research lab, the child has a history of 
[symptoms]. 
 
Results related to the reason for testing (also called primary results): 
No genetic changes report (also called a negative result) 
Result 
• 
The whole genome sequencing test was not able to find a genetic cause for your child’s symptoms. 
• 
It is still possible that your child’s symptoms have a genetic cause. Current tests cannot find or 
understand all of the genetic changes that may cause health problems. 
Future care 
• 
No test is perfect. Genetic testing will continue to change and improve over time, as will the 
knowledge of how genetic changes can cause health problems. 
• 
Other genetic tests may be needed for your child based on [his/her] personal and family medical 
histories. Please continue follow-up with your child’s healthcare providers to learn about new 
information, testing options, or research studies. 
 
Results NOT related to the reason for testing (also called secondary results): 
Disease-causing genetic change found (also called a positive result) 
Result 
• 
A change was found in one copy of your child’s APOB gene. 
• 
Changes in the APOB gene have been seen in people with high cholesterol. Based on this result 
your child may have an increased chance to have high cholesterol. 
Chance family members could have the same genetic change (recurrence risk) 
• 
This APOB gene change was inherited from your child’s mother. Other relatives on your child’s 
mother’s side of the family, including your child’s brothers and sisters, may also have this change 
and want to discuss this with their doctors. 
Future care 
• 
Your child’s doctors and nurses may talk with you about changes to your child’s care based on this 
result. 
• 
Please see the attached lab report for more specific information about this genetic change. 

Page 2 of 2 
 
This test looked at 59 genes* that can cause disease in the future. Humans have more than 20,000 
genes. There are many gene changes that may cause disease that the lab cannot find or 
understand. 
For More Information: 
• 
About [insert gene/condition]: 
• 
[Insert Source]: [insert link] 
• 
For support related to [insert gene/condition]: [insert link] 
 
 
 
Participant Name: 
Participant ID#: 
Participant DOB: 
Report Date: 
 
 
 
 
 
 
 
 
 
If you have questions, please contact your child’s healthcare team at the NICU where [he/she] 
was enrolled. 
You may also contact a study genetic counselor at the information below. 
 
 
 
Kelly East, MS, CGC 
Certified Genetic Counselor 
HudsonAlpha Institute for Biotechnology 
256-327-0461 
 
 
 
 
 
 
 
 
Information about the test 
Keep this information for future use 
 
Whole genome sequencing was done on a research basis at the HudsonAlpha Institute for Biotechnology 
(not in a CAP/CLIA environment). Sequencing was done on an Illumina HiSeq X sequencer at an 
approximate depth of 30X. Variant pathogenicity was determined using ACMG criteria. 
 
In addition to the affected child, laboratory reports may be available for parent samples. The last digit of 
the “ID2” section of the laboratory report header indicates whether a report is for the child/proband (P), 
mom (M), or dad (D). 
 
*Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 
update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. 
Genet Med. 2017. https://www.nature.com/articles/gim2016190 

Page 1 of 2 
 
 
Participant Name: 
Participant ID#: 
Participant DOB: 
Report Date: 
 
This letter describes genetic test results from the SouthSeq research study (research protocol No. 
300000328). 
Your child was enrolled because he or she was in the neonatal intensive care unit (NICU) and 
had symptoms that may be due to a genetic problem. 
Reason for testing: Based on information provided to the research lab, the child has a history of 
[symptoms]. 
 
Results related to the reason for testing (also called primary results): 
Genetic change was found (also called a positive result) 
Result 
• 
The whole genome sequencing test found a change in the SATB2 gene that is likely the reason for 
most or all of your child’s symptoms. 
• 
Changes in this gene have been seen in people with Glass syndrome. 
• 
People with glass syndrome can have difficulty learning, speech delay, and certain physical 
differences. 
Chance that family members could have the same genetic change (recurrence risk) 
• 
This genetic change was new in your child and not found in the blood of either parent. The chance 
that these two parents have another child together with the same genetic change is less than 1% 
(less than 1 in 100). 
• 
For your child, the chance of having a child with the same SATB2 change is 50% (1 in 2). 
Future care 
• 
Your child’s doctors and nurses may talk with you about changes to your child’s care based on this 
result. 
• 
Other genetic tests may be needed for your child based on [his/her] personal and family medical 
histories. 
• 
Please continue follow-up with your child’s healthcare providers to learn about new information, 
testing options, or research studies. 
• 
Please see the attached lab report for more specific information about this genetic change. 
 
Results NOT related to the reason for testing (also called secondary results): 
No other genetic changes found (also called a negative result) 
Keep in mind: 
• 
In addition to looking for the reason for your child’s symptoms, this test looked at 59 other genes* 
that can cause disease in the future. 
• 
The whole genome sequencing test did not find any specific genetic changes associated with risk 
of developing a disease in the future. 

Page 2 of 2 
 
• 
This does not mean your child will not develop a genetic disease in the future. Humans have more 
than 20,000 genes. There are many gene changes that may cause disease that the lab cannot find 
or understand. 
For More Information: 
• 
About [insert gene/condition]: 
• 
[Insert Source]: [insert link] 
• 
For support related to [insert gene/condition]: [insert link] 
 
Participant Name: 
Participant ID#: 
Participant DOB: 
Report Date: 
 
 
 
 
If you have questions, please contact your child’s healthcare team at the NICU where [he/she] 
was enrolled. 
You may also contact a study genetic counselor at the information below. 
 
 
Kelly East, MS, CGC 
Certified Genetic Counselor 
HudsonAlpha Institute for Biotechnology 
256-327-0461 
 
 
 
 
 
 
 
Information about the test 
Keep this information for future use 
 
Whole genome sequencing was done on a research basis at the HudsonAlpha Institute for Biotechnology 
(not in a CAP/CLIA environment). Sequencing was done on an Illumina HiSeq X sequencer at an 
approximate depth of 30X. Variant pathogenicity was determined using ACMG criteria. 
In addition to the affected child, laboratory reports may be available for parent samples. The last digit of 
the “ID2” section of the laboratory report header indicates whether a report is for the child/proband (P), 
mom (M), or dad (D). 
 
*Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 
update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. 
Genet Med. 2017. https://www.nature.com/articles/gim2016190 

Page 1 of 2 
 
 
Participant Name: 
Participant ID: 
Participant DOB: 
Report Date: 
 
This letter describes genetic test results from the SouthSeq research study (research protocol No. 
300000328). 
Your child was enrolled because he or she was in the neonatal intensive care unit (NICU) and 
had symptoms that may be due to a genetic problem. 
Reason for testing: Based on information provided to the research lab, the child has a history of 
[symptoms]. 
 
Results related to the reason for testing (also called primary results): 
Genetic change was found (also called a positive result) 
Result 
• 
The whole genome sequencing test found two changes in the DHCR7 gene that together are likely 
the reason for most or all of your child’s symptoms. 
• 
Changes in this gene have been seen in people with Smith-Lemli-Optiz syndrome (SLOS). 
• 
People with SLOS can have learning difficulties and certain facial and physical differences. 
Chance that family members could have the same genetic changes (recurrence risk) 
• 
One of the genetic changes was found in her mother’s blood. The other genetic change was found 
in her father’s blood. 
• 
Having one genetic change in DHCR7 does not cause SLOS. One change means someone is a 
carrier for SLOS. 
• 
When two carriers of SLOS have a child together, there is a 25% (1 in 4) chance with each 
pregnancy to have a child with SLOS. 
Future care 
• 
Your child’s doctors and nurses may talk with you about changes to your child’s care based on this 
result. 
• 
Other genetic tests may be needed for your child based on [his/her] personal and family medical 
histories. 
• 
Please continue to follow-up with your child’s healthcare providers to learn about new information, 
testing options, or research studies. 
• 
Please see the attached lab report for more specific information about these genetic changes. 
 
Results NOT related to the reason for testing (also called secondary results): 
No other genetic changes found (also called a negative result) 
Keep in mind: 
• 
In addition to looking for the reason for your child’s symptoms, this test looked at 59 other genes* 
that can cause disease in the future. 

Page 2 of 2 
 
• 
The whole genome sequencing test did not find any specific genetic changes associated with risk 
of developing a disease in the future. 
• 
This does not mean your child will not develop a genetic disease in the future. Humans have more 
than 20,000 genes. There are many gene changes that may cause disease that the lab cannot find 
or understand. 
For More Information: 
About [insert gene/condition]: [insert linik] 
Genetics Home Reference 
GeneReviews 
For support related to [insert gene/condition]: [insert link] 
 
Participant Name: 
Participant ID: 
Participant DOB: 
Report Date: 
 
 
 
 
If you have questions, please contact your child’s healthcare team at the NICU where [he/she] 
was enrolled. 
You may also contact a study genetic counselor at the information below. 
 
 
Kelly East, MS, CGC 
Certified Genetic Counselor 
HudsonAlpha Institute for Biotechnology 
256-327-0461 
 
 
 
 
 
 
 
Information about the test 
Keep this information for future use 
 
Whole genome sequencing was done on a research basis at the HudsonAlpha Institute for Biotechnology 
(not in a CAP/CLIA environment). Sequencing was done on an Illumina HiSeq X sequencer at an 
approximate depth of 30X. Variant pathogenicity was determined using ACMG criteria. 
In addition to the affected child, laboratory reports may be available for parent samples. The last digit of 
the “ID2” section of the laboratory report header indicates whether a report is for the child/proband (P), 
mom (M), or dad (D). 
 
*Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 
update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. 
Genet Med. 2017. https://www.nature.com/articles/gim2016190 

Page 1 of 3 
 
 
 
 
Participant Name: 
Participant ID#: 
Participant DOB: 
Report Date: 
 
This letter describes genetic test results from the SouthSeq research study (research protocol No. 
300000328). 
Your child was enrolled because he or she was in the neonatal intensive care unit (NICU) and 
had symptoms that may be due to a genetic problem. 
Reason for testing: Based on information provided to the research lab, the participant has a 
history of [symptoms]. 
 
Results related to the reason for testing (also called primary results): 
Uncertain genetic change found (also called an uncertain result) 
Result 
• 
The whole genome sequencing test found a change in the TPM3 gene. Some changes in the TPM3 
gene have been seen in people with several forms of myopathy, or muscle weakness. 
• 
The specific TPM3 gene change found in your child has not been seen before. The lab is not sure 
whether it can cause symptoms or is just a harmless (benign) gene change. 
Chance that family members could have the same genetic change (recurrence risk) 
• 
This genetic change was inherited from your child’s mother who has not reported symptoms. The 
child’s mother may need to have further testing to look for any signs or symptoms of the condition. 
• 
The chance that your child’s mother will have another child with the same genetic change is 50% 
(1 in 2). 
• 
For your child, the chance of having a child with the same TPM3 change is also 50% (1 in 2). 
• 
Because the meaning of this change is unknown, future children with the same TPM3 gene change 
may not necessarily have health problems. This result should not be used to predict symptoms in 
other children or family members until it is better understood. 
Future care 
• 
Your child’s doctors and nurses offer your child more tests or exams that would help them learn 
whether this change is the cause of your child’s symptoms. However, most of the time an uncertain 
genetic result will not change your child’s care. 
• 
If the lab gets more information about this change during the course of the research study, your 
child’s doctor will get an updated report. 
• 
Other genetic tests may be needed for your child based on [his/her] personal and family medical 
histories. Please continue to follow-up with your child’s healthcare providers to learn about new 
information, testing options, or research studies. 
• 
Please see the attached lab report for more specific information about this genetic change. 

Page 2 of 3 
 
For More Information: 
• 
About [insert gene/condition]: 
• 
[Insert Source]: [insert link] 
• 
For support related to [insert gene/condition]: [insert link] 
 
 
 
Participant Name: 
Participant ID#: 
Participant DOB: 
Report Date: 
 
 
 
 
Results NOT related to the reason for testing (also called secondary results): 
No other genetic changes reported (also called a negative result) 
Keep in mind: 
• 
In addition to looking for the reason for your child’s symptoms, this test looked at 59 other genes* 
that can cause disease in the future. 
• 
The whole genome sequencing test did not find any specific genetic changes associated with risk 
of developing a disease in the future. 
• 
This does not mean your child will not develop a genetic disease in the future. Humans have more 
than 20,000 genes. There are many gene changes that may cause disease that the lab cannot find 
or understand. 
 
 
 
If you have questions, please contact your child’s healthcare team at the NICU where [he/she] 
was enrolled. 
You may also contact a study genetic counselor at the information below. 
Kelly East, MS, CGC 
Certified Genetic Counselor 
HudsonAlpha Institute for Biotechnology 
256-327-0461 
 
 
 
 
 
Information about the test 
Keep this information for future use 
 
Whole genome sequencing was done on a research basis at the HudsonAlpha Institute for Biotechnology 
(not in a CAP/CLIA environment). Sequencing was done on an Illumina HiSeq X sequencer at an 
approximate depth of 30X. Variant pathogenicity was determined using ACMG criteria. 
In addition to the affected child, laboratory reports may be available for parent samples. The last digit of 
the “ID2” section of the laboratory report header indicates whether a report is for the child/proband (P), 
mom (M), or dad (D). 

Page 3 of 3 
 
 
 
 
Participant Name: 
Participant ID#: 
Participant DOB: 
Report Date: 
 
 
*Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 
update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. 
Genet Med. 2017. https://www.nature.com/articles/gim2016190 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 2: Decliner Survey 

1. Please identify the individual completing this survey. 
 Mother 
 Father 
 Other (please specify):  
 
 
2. What is your date of birth? --/--/---- 
 
3. What category or categories best describe you? Check all that apply. 
 American Indian, Native American, or Alaskan Native 
 Asian 
 Black or African American 
 Native Hawaiian/Pacific Islander 
 White or European American 
 Middle Eastern or North African/Mediterranean 
 Hispanic/Latino(a) 
 Prefer not to answer 
 Unknown/None of these fully describe me 
 
4. What category or categories best describe your child? Check all that apply. 
 American Indian, Native American, or Alaska Native 
 Asian 
 Black or African American 
 Native Hawaiian/Pacific Islander 
 White or European American 
 Middle Eastern or North African/Mediterranean 
 Hispanic/Latino(a) 
 Prefer not to answer 
 Unknown/None of these fully describe my child 
5. What is the highest grade or level of school you completed or the highest degree you 
received? (Check one) 
 No schooling completed 
 Elementary school (kindergarten through 5th grade) 
 Middle school (6th, 7th, or 8th grade) 
 Some high school (9th, 10th, or 11th grade) 
 12th grade, no diploma 
 High school graduate (diploma or GED or equivalent) 
 Some post-high school training (college or occupational, technical, or vocational 
training), no degree or certificate 
 Completed occupational, technical, or vocational program, received degree or 
certificate 
 Associate (2-year) college degree 
 Bachelor’s degree (for example: BA, AB, BS) 
 Master’s degree (for example: MA, MS, MEng, MEd, MSW, MBA) 
 Professional degree (for example: MD, DDS, DVM, LLB, JD) 
 Doctoral degree (for example: PhD, EdD) 

Instructions for investigator: please select every box that corresponds to the 
reasons given for non-participation in the free text above. 
6. Please tell us why you decided not to join this study: [open response] 
 
Study 
 The study will take too much of my time/too busy/no time 
 The study does not give me enough money for the amount of time it requires from 
me 
 The study location or visits are not convenient for me/too far/unable to travel/no 
transportation 
 I do not wish to give the study samples (blood, saliva, etc.) 
Privacy 
 Results are stored in my/my child’s electronic health record 
 My/my child’s genetic results could be seen by: 
 The government 
 My employer 
 My insurance company 
 My/my child’s genetic results could be used to discriminate against me/my child by 
my: 
 
 
 
 
Health 
 Health Insurance 
 Life Insurance 
 Long-Term Care Insurance 
 Disability Insurance 
 Other [Free Text] 
 I am overwhelmed by my own/my child’s health problems right now 
 I do not want more testing than my own/my child’s doctor recommends 
 I am too ill 
Do not want certain types of genetic results 
 Results that aren’t related to my own/my child’s health problems right now 
 Results that only cause health problems in adults 
 Results that don’t affect my health but could be important for my children or other 
family members 
 Results that are uncertain 
 Results about conditions with no treatment 
Other 
 Religious/spiritual reasons 
 Genetic test results may affect my family relationships 
 I want my child to choose for him/herself when he/she is an adult 
 Not interested in [my child] participating in research (general)/Not interested in [my 
child]participating in genetics research 
 Too many other competing demands (caring for others, long work hours) 
 Other [Free Text] 
 
 REFUSED TO ANSWER/NO REASON PROVIDED 

7.  [OPTIONAL] This list is from other patients/parents who decided not to join studies like 
this one. Did any of these reasons affect your decision not to join this study? Please 
choose up to three reasons. 
 
 The things I/my child need to do to be in the study didn’t work well for me 
 I have concerns about my privacy 
 I am not interested in participating in research 
 My/my child’s current health condition is all I want to focus on right now 
 I don’t want genetic research results from this study 
 I’m worried about how I will cope with the genetic information I might receive 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 3: Informed Consent Forms (Site‐Specific) 

Page 1 of 15 
Version Date: 02/14/2020 
 
 
 
 
CONSENT FORM 
Title of Research: 
South-seq: DNA sequencing for newborn nurseries in the South 
(NIH Grant Number 2U01HG007301-05) 
UAB IRB Protocol #: 
IRB-300000328 
Principal Investigators: 
Bruce Korf MD, PhD 
 
Sponsor: 
NIH National Human Genome Research Institute 
(Contact: Lucia Hindorff PhD, MPH) 
UAB IRB 
Approved 
04-Mar-2020 
until 
27-Aug-2020 
 
 
Purpose of the Research 
We are asking you to take part in a research study. The purpose of this research study is to use 
whole genome sequencing (WGS), looking at your DNA, to identify the genetic cause of conditions 
like those observed in your child. For individuals with rare, undiagnosed diseases and their families, 
this experimental genetic test may provide information about what is causing the disease or 
condition. This information may be beneficial to your family in directing your child’s health care, 
medical treatments, and your family planning decisions. Educational tools about your child’s 
condition may also become available with a confirmed genetic diagnosis. 
 
In addition, due to the limited number of genetic counselors available to support patients that may 
benefit from WGS, we will be comparing two results delivery methods: genetic counselors (standard 
of care), and healthcare providers (e.g. neonatologists and neonatology nurse practitioners) who 
undergo specific genetics results delivery training. In this clinical trial, we aim to demonstrate that 
both delivery methods are equivalent (i.e. there is no difference between the two methods). In 
order to so this, we plan to record the return of results conversations that you will have as part of 
this study. 
Due to the experimental nature of this research study, data generated is based upon the knowledge 
currently accepted in the field. As more genomes are sequenced and as sequencing techniques 
improve, we will be better at identifying and understanding extremely rare variants (rare changes in 
DNA). In doing this, we will learn more about how certain variants may cause disease. For this 
reason, we plan to store samples for future research. 
There will be approx. 1500 newborn participants enrolled for WGS, and 800 parents and caregivers 
enrolled for the clinical trial across 6 NICU sites: UAB/Children’s of Alabama, University of Mississippi 
Medical Center (UMMC), Woman’s Hospital, University of Louisville and Norton Healthcare (UofL). 
Samples will also be collected from biological mothers and fathers (up to 2,250 individuals), when 
available, so that we can use their samples to determine inheritance of any variants we find in their 
child. We also hope to include a diverse group of participants so we are planning to offer this test to 
For Children (persons under 18 years of age) participating in this study, the term “You” addresses both 
the participant ("you") and the parent or legally authorized representative ("your child"). 

Page 2 of 15 
Version Date: 02/14/2020 
 
all populations, especially those underrepresented in science and genomic research such as African 
Americans and those from rural areas. 
Explanation of Procedures 
 
If you agree to join the study, you are agreeing to: 
● Give us permission to collect a blood sample for DNA analysis 
o Adults will give approximately 8mL (approx. 1.6 tsp) of blood that will be drawn from 
the arm. 
o Newborns will give no more than the maximum amount allowed for their body weight 
according to the Children’s Of Alabama guidelines. 
● Give us permission to fully analyze your DNA (or other related material, like RNA or 
protein) and determine the health significance of your genetic results. 
● Allow us to return health information to you that we feel may be important to your child’s 
health or other biological relatives. 
● Allow key study personnel to access your child’s personal medical records to aid in analysis. 
Study personnel may collect information about the child’s symptoms, health history, 
medications/treatments, etc. 
● Provide key study personnel with information about your child’s health history, pregnancy and 
birth history, information about your health and that of other family members, if you know it, 
etc. Study personnel will not access your medical record. They will only have access to the 
information that you choose to share with them. 
● Allow us, if you so choose, to return genetic results that are not related to your child’s 
condition but are medically important for other reasons. 
● Answer survey questions at 5 time points: the time of consent, return of results (ROR) 
appointment, 1-month post-ROR, 4-months post-ROR, and 4.5-months post-ROR. Each survey 
will take approximately 20-35 minutes to complete. 
You will be asked to take part in two clinic visits here in the nursery or at the outpatient clinic. 
During the first visit, you will be asked to enroll in the study and give a blood sample (1.5hrs) and 
during the second visit you will receive the results of your child’s DNA test either by a genetic 
counselor or a trained healthcare provider (1.5-2hrs). The return of results visit can either take 
place in-person or over the phone. A certified letter with results will be sent to those who do not 
participate in either in the in-person or phone ROR appointment. 
More than one parent/guardian/caregiver of a child receiving WGS can participate in the study. It is 
important that anyone participating in the survey portion of the study be present at ROR and 
complete every survey. 
Collecting samples from both biological parents increases the chances of identifying genetic 
variation in your child that might be causing his or her symptoms. However if both parents are not 
available, we can still analyze eligible patients and potentially find valuable information. In cases 
where we enroll family members, our DNA test can identify whether a person is the biological 
parent or not. We will not tell you or your family members if we find out that one or both parents 

Page 3 of 15 
Version Date: 02/14/2020 
 
are not biologically related to the child, however we are less likely to discover diagnostic 
information about your condition without both biological parents. 
Your blood samples will be labeled with a unique code (coded) and sent to researchers at the 
HudsonAlpha Institute for Biotechnology, a non-profit genetics research center located in 
Huntsville, AL. Some relevant, health information will also be given to the research staff, and 
coded with a unique study identifier, to aid in their analysis. 
 
We will use state-of-the-art technologies to generate large amounts of information about the DNA 
from you and your child. A group of experts, including medical doctors and researchers, will use 
scientific findings and genetic databases to help decide what genetic information may be 
important to the health of your child. The sequence of all results believed to be medically relevant 
or important to your child’s or your own health will be validated at HudsonAlpha Clinical Services 
Laboratory in Huntsville, AL or another independent clinical laboratory. We expect the entire DNA 
analysis process to take 2-4 months. 
 
We do intend to perform analysis of each sample within our budgetary and technical means. If we 
are unable to analyze your samples you will be notified within 6 months of enrollment and sample 
collection. There is no cause for concern if you are told that we could not complete the analysis 
and provide you with results. 
 
Return of results is at the discretion of the clinicians and researchers involved with this study. If 
they identify results that may impact your child’s health, they may return those results to you. You 
will be scheduled for an appointment to discuss these findings with a genetic counselor or a 
trained healthcare provider. Only a subset of results believed to be important to your child’s 
medical care or those in line with the goals of this study will be reported to you. We will not 
provide you with all of the genetic information that we generate. At your results appointment, 
you may be provided with information regarding: 
● Primary findings - These findings will include information about a variant(s) (DNA change) 
that may potentially be the reason for your child’s symptoms or condition. 
o Most children will not receive a primary finding (or diagnosis). If no diagnosis is 
found, we will tell you. Even if we do not find a genetic diagnosis, your condition 
may still be the result of a change in your DNA that we are currently unable to 
identify. 
o If you receive a genetic diagnosis, this may not change your child’s prognosis or 
medical treatment. However it may help you and your doctor to better understand 
the cause of your child’s condition and the risks of similar conditions affecting your 
biological children. 
● Secondary findings – These findings may be reported to any study participant and may 
include any genetic changes that might impact your health or the health of your current or 
future children. These may include: 
o Whether there are any changes in your DNA that could put you at a higher risk for 
developing a disease unrelated to your child’s condition in the future, such as cancer 
or heart disease. 

Page 4 of 15 
Version Date: 02/14/2020 
 
1. Some of these diseases may be medically useful and some may not be 
medically useful. We will not return results that are not medically useful. 
2. Some of these diseases will appear in childhood and others will appear 
when you are an adult. 
● Carrier status – In the event that we discover that your child’s symptoms are caused by a 
recessive genetic condition where he or she inherited one variant (DNA change) from each 
parent, we may provide information about whether or not you are a "carrier" for a genetic 
change that may be passed on to your biological children. 
We will arrange for a genetic counselor or a trained healthcare provider to discuss the results of 
the test with you. Educational materials will also be made available to you to help you better 
understand any results that you may or may not receive as part of this study. 
You will be actively enrolled in this study for up to one year however, we may continue to access 
your medical record for up to 5 years. We plan to use coded information from our medical record 
to determine the impact of whole genome sequencing and genetic diagnosis on medical care. 
After you receive the results of the genetic test, you may be contacted by your physician or key 
study personnel to check on you or to ask follow-up questions. Your DNA samples may be stored 
indefinitely for future research unless you choose to withdraw from the study. Please note that 
participation in this study is voluntary and you may withdraw from this study at any time. 
You will also be presented with a baseline survey at the time of enrollment that you can complete 
online using Genome Gateway. The survey will ask you questions about basic demographics, how 
you feel about your child’s health and your experience in the hospital, how well you understand 
medical terms, math and genetics. After you receive results, you will be asked some of these same 
questions and some additional ones related to your health, your understanding of the genetics 
results returned, and how the results influence future planning at 1-month post-ROR, 4-months 
post-ROR, and 4.5-months post-ROR. 
 
Risks and Discomforts 
The risks of drawing blood include pain, bruising, lightheadedness, and fainting. Infection at the site 
of the needle stick is a rare side effect. These are the same risks you face any time you have a blood 
test. 
 
The main concerns associated with genetic testing are anxiety, depression, or other forms of 
emotional distress that may result from receiving genetic information about the suspected cause of 
your child’s condition. This is especially true for those diseases that are not treatable or preventable. 
Though some treatments have been shown to help individuals with certain genetic conditions, there 
is no "cure" for most. 
 
When performing genetic testing, it may be discovered that family relationships are not as predicted. 
For example, a child might not be biologically related to his/her father, or two people who are 
married might turn out to be biologically related. These findings will not be disclosed as part of this 
study. 

Page 5 of 15 
Version Date: 02/14/2020 
 
In some cases, you may receive information about your carrier status and/or changes in your DNA 
that may impact your health. These findings will only be returned if they were inherited by your child 
who is enrolled in this study and suspected to contribute to their condition. Genetic changes in 
children that affect development may be inherited from one or both parents, even if the parents 
appear to be healthy. This information may affect the way you view or evaluate yourself or your 
family. It may also influence, or generate anxiety about, future family planning decisions. 
It is also important to keep in mind that you and your biological relatives have similar DNA 
sequences. This means that genetic information about your child may also have implications for your 
relatives if the variation was inherited. 
You may be referred to an additional physician or clinic for further testing or advice depending on 
the type of genetic information we generate from your sample. If you experience psychological 
distress or other difficulties, we can also refer you to an appropriate resource for care and/or 
support. 
 
There may be unforeseeable risks associated with receiving genetic information and the potential 
decisions, actions, or inactions that may be required in response to that information. Please consider 
this carefully and ask any questions that you may have before deciding whether or not to participate 
in this study. 
 
It is important that you consider the risks and uncertainties of this research study that make it 
different from traditional medical testing. 
 
We will make sure that the information that you are given is as accurate as possible to the best of 
our ability. We will use the best standards, practices, and technologies available to researchers. 
However, the technologies available to analyze DNA and our knowledge of how DNA affects health 
are changing rapidly. They are also subject to much uncertainty. Some DNA changes that are 
important to health may be missed, and other DNA changes that are not important may be 
incorrectly identified as if they are important. There are also moral and ethical questions about using 
genetic information on which scientific and medical communities have not yet reached a consensus. 
Therefore, we do NOT guarantee that our test will have the same levels of completeness, accuracy, 
or standardization associated with more traditional medical tests. 
 
Before offering your consent to participate in this research study, please consider all of the risks 
associated with: 
● The return or possible lack of return of results; 
● Whether our interpretation of those results is accurate; 
● How you and/or your family will choose to act upon or not act upon the information or lack 
of information. 

Page 6 of 15 
Version Date: 02/14/2020 
 
Benefits 
You may not benefit directly from taking part in this study. However, your participation may lead to 
new discoveries that help to advance medical research and improve patient care, especially, but not 
only, newborn patient care in the future. Your participation in this study may help to make health 
care and access to health care broader and more representative. 
You may find out if there is a change in your child’s DNA that has altered their development. You 
might also find out if this change could affect future biological children. 
A genetic diagnosis may help you connect with other families in the community who face similar 
medical problems. While unlikely, it is possible that a genetic diagnosis may point your doctor to a 
better medical and/or educational treatment. 
You may discover that you or your child are at an increased risk for developing other diseases and 
that information may be of medical benefit. 
 
None of the above benefits are guaranteed, and it is expected that many participants will not receive 
specific information that is relevant to their health. 
 
Alternatives 
This is not a treatment study. Your alternative is not to participate in this research study. 
 
Confidentiality 
Information obtained about you for this study will be kept confidential to the extent allowed by law. 
However, research information that identifies you may be shared with people or organizations for 
quality assurance or data analysis, or with those responsible for ensuring compliance with laws and 
regulations related to research. They include: 
● the UAB Institutional Review Board (IRB). An IRB is a group that reviews the study to protect 
the rights and welfare of research participants. 
● the NIH National Human Genome Research Institute (NHGRI) 
● the Office for Human Research Protections (OHRP) 
 
The information from the research including your child’s clinical information, family history, and 
genetic variants may be published for scientific purposes; however, your identity will not be given out 
to anyone outside of the clinical team involved with the study. 
 
Your consent form will be placed in your child’s medical record at UAB Health System or UMMC. This 
may include either a paper medical record or electronic medical record (EMR). An EMR is an 
electronic version of a paper medical record of your care within this health system. Your child’s EMR 
may indicate that you and your child are enrolled in this study and provide the name and contact 
information for the principal investigator. 

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Results of research tests or procedures that have been clinically validated (i.e. Sanger reports) may be 
placed in your child’s medical record. All information within your medical record can be viewed by 
individuals authorized to access the record. 
Information relating to this study, including your name, medical record number, date of birth and 
social security number, may be shared with the billing offices of UAB and UAB Health System 
affiliated entities or UMMC so costs for clinical services can be appropriately paid for by either the 
study account or by your insurance. 
This research is covered by a Certificate of Confidentiality from the National Institutes of Health. The 
researchers with this Certificate may not disclose or use information, documents, or biospecimens 
that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other 
action, suit, or proceeding, or be used as evidence, for example, if there is a court subpoena, unless 
you have consented for this use. Information, documents, or biospecimens protected by this 
Certificate cannot be disclosed to anyone else who is not connected with the research except, if there 
is a federal, state, or local law that requires disclosure (such as to report child abuse or communicable 
diseases but not for federal, state, or local civil, criminal, administrative, legislative, or other 
proceedings, see below); if you have consented to the disclosure, including for your medical 
treatment; or if it is used for other scientific research, as allowed by federal regulations protecting 
research subjects. 
A federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes it illegal 
for health insurance companies, group health plans, and some employers to discriminate against you 
based on your genetic information. This law generally will protect you in the following ways: 
● Health insurance companies and group health plans may not request your genetic information 
that we get from this research. 
● Health insurance companies and group health plans may not use your genetic information 
when making decisions regarding your eligibility or premiums. 
● Employers with 15 or more employees may not use your genetic information that we get from 
this research when making a decision to hire, promote, or fire you or when setting the terms 
of your employment. 
 
Be aware this federal law does not protect you against genetic discrimination by companies that sell 
life insurance, disability insurance, or long-term care insurance, nor does it protect you against 
genetic discrimination by some employers. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web site 
will include a summary of the results. You can search this Web site at any time. 
Voluntary Participation and Withdrawal 
Whether or not you take part in this study is your choice. There will be no penalty if you decide not to 
be in the study. If you decide not to be in the study, you will not lose any benefits you are otherwise 

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owed. You are free to withdraw from this research study at any time. Your choice to leave the study 
will not affect your relationship with any institution participating in this study. 
In the event that you chose to withdraw from the study: 
● No further genetic information from the study will be reported to you. 
● Your blood samples will be destroyed. 
● You will not be contacted to provide new information, additional samples, or 
participate in additional studies related to this project. 
● If the analysis of your DNA has been completed, this information will be retained for the 
study. 
If you would like to withdraw from the study, please contact Dr. Bruce Korf at 205-934-9411. 
Cost of Participation 
There will be no cost to you for taking part in this study. The blood draw, genomic sequencing and 
analysis, and genetic counseling related to this study will be provided to you at no cost during the 
study period. 
 
After you receive your research results, you may decide with your doctor or your child’s doctor to 
get more testing. The costs of your standard medical care or any services rendered in response to a 
genetic finding identified by this research project will be billed to you and/or your insurance 
company in the usual manner. This type of follow-up medical testing will be considered part of your 
clinical care, and will not be paid for by the research study. 
 
Payment for Participation in Research 
Participation in this study is voluntary and $25 will be provided for each survey completed for a total 
of $125 for your completion of all 5 study-related surveys. Ask the study staff about the method of 
payment that will be used for this study (e.g., check, cash, gift card, direct deposit); payment may 
take up to 4 weeks to process. 
 
Payment for Research-Related Injuries 
UAB, UMMC, HudsonAlpha and NIH/NHGRI/sponsors of this research project have not provided for 
any payment if you are harmed as a result of taking part in this study. If such harm occurs, treatment 
will be provided. However, this treatment will not be provided free of charge. 
 
Significant New Findings 
The study doctor or study staff will tell you if new information becomes available that might affect 
your choice to stay in the study. Please note that HudsonAlpha may, but is not required to, reanalyze 
your sample or report any new findings after results have been returned. 
 
Storage of Specimens for Future Use 
As part of this study, we would like to store some of the blood and DNA specimens collected from 
you and your child for validation of variants (to determine if a variant was inherited from a parent, 
etc.) identified by this project and for future research relevant to rare disease or other genetic 

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disorders. The future research may be conducted by the study doctor or by other researchers that 
obtain IRB approval for their research. The specimens will be labeled with a code that only the study 
doctor can link back to you. Results of any future research will not be given to you or your doctor. The 
specimens obtained from you in this research may help in the development of a future commercial 
product. There are no plans to provide financial compensation to you should this occur. You do not 
have to agree to allow your specimens to be stored in order to be part of this study. 
You may at any time withdraw from the study and request that your specimens be removed from 
storage and not be used for future research. If you decide you want your specimens removed, you 
may contact Dr. Bruce Korf at 205-934-9411. Once the request is received, and if your samples have 
not already been used for other research, they will be destroyed. If you do not make such a request, 
your specimens will be stored indefinitely or until used. 
Initial next to your choice below: 
 
I agree to allow my specimens to be kept in the HudsonAlpha CSL and used for future genetics 
research. 
 
 
I do NOT agree to allow my specimens to be kept and used for future research. 
 
Genomic Data Sharing (GDS) 
We consider the privacy of your information to be of high priority and will take a variety of steps to 
ensure that privacy. However it is important for researchers to share some of the information that 
they learn from studying human samples. We will never share personally identifiable information, 
like names and addresses, with anyone outside of the research study. However, parts of your 
information may be shared. 
 
Some of your genetic information, limited to a very small subset that will not cause privacy loss risks 
to you, may be published in scientific journals or other unrestricted-access public venues to 
encourage sharing of the knowledge that may be learned by analyzing your DNA and DNA from other 
individuals. This could include information about your child’s symptoms, their age, and any genetic 
findings that we discover. 
 
We may share coded lists of the DNA differences that we identify in public genetic databases. These 
databases gather genetic information from large groups of people and are pooled together such that 
no specific participant can be identified. 
 
There is a very small chance that some commercial value may result from the use of your donated 
samples or genetic information. If that happens, you will not receive a share in any profits. 
 
Unless you opt out, we may submit your complete genomic data along with some of your coded 
health information to an NIH-designated Data Repository such as dbGAP 
(http://www.ncbi.nlm.nih.gov/gap), AnVIL (https://anvilproject.org/), or another controlled access 
database. Access to dbGAP and AnVIL is only available to qualified researchers at qualified 

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institutions who have agreed to abide by certain privacy safeguards, obligating them, both legally 
and ethically, to protect your privacy and to maintain information confidentiality. However, since 
your genetic information is unique to you, there is a small chance that someone could trace your 
information back to you. This risk is very small, but may grow in the future. Some risks and benefits 
are listed below: 
Risks: The risk of sharing your genomic data is that someone could link the information stored 
in the databases back to you. If your information suggests something about your health such 
as increased risk for disease, it could be misused. For example, it could be used to make it 
harder for you to get or keep a job or insurance or be used to discriminate against you or your 
family. There may also be other unknown risks. As stated above (confidentiality section of this 
form), there are federal protections against the misuse of your data (i.e. the Genetic 
Information Nondiscrimination Act, GINA). 
Benefits: There is no direct benefit to you from sharing your genomic data with NIH- 
designated data repositories, however allowing researchers to use your data may lead to a 
better understanding of how genes affect health which may help other people in the future. 
 
Initial next to your choice below: 
 
 
 I agree for my genetic and other relevant study data, such as health information, to be shared 
with NIH-designated repositories such as dbGAP and AnVIL in a coded form for future research 
or analysis 
 
 I do NOT agree for my genetic and other relevant study data, such as health information, to be 
shared with NIH-designated repositories such as dbGAP and AnVIL in a coded form for future 
research or analysis 
 
Contact For Future Research 
As new research opportunities are identified, the researchers may wish to perform additional tests 
on fresh samples or invite eligible participants to enroll in new studies. We would like permission to 
contact you in the future, however this is not a requirement to participate in this study. A separate 
consent form will be obtained if you wish to participate in future research. 
 
Initial next to your choice below: 
 
 
 
You have permission to contact me about new research opportunities that may interest me. 
 
 
 
You do NOT have permission to contact me about new research opportunities. 

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Secondary Findings 
One unanimous decision to receive or not to receive secondary findings must be made by each 
participant family. Because parental samples are only used for confirmation of variation identified in 
the child’s whole genome sequence for this project, only those secondary findings identified in the 
child will be confirmed in the parental samples. Participant families may opt to receive this 
information, if available. If a family chooses to do so, information about an identified secondary 
finding will be included in the child’s medical record. Nothing will be placed in the parent’s medical 
record. 
Initial next to your choice below: 
 
 
 We (child and parent(s), if enrolled) would like to receive information about secondary 
findings. 
 
 
 We (child and parent(s), if enrolled) would NOT like to receive information about secondary 
findings. 
Questions 
If you have any questions, concerns, or complaints about the research or a research-related injury 
including available treatments, please contact Dr. Bruce Korf at 205-934-9411. 
 
If you have questions about your rights as a research participant, or concerns or complaints about the 
research, you may contact the UAB Office of the IRB (OIRB) at (205) 934-3789 or toll free at 1-855- 
860-3789. Regular hours for the OIRB are 8:00 a.m. to 5:00 p.m. CT, Monday through Friday. 
 
Legal Rights 
You are not waiving any of your legal rights by signing this consent form. 

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Signatures 
Your signature below indicates that you have read (or been read) the information 
provided above and agree to have your child participate in this study. You will receive a copy of this 
signed consent form. 
Your signature below indicates that you have read (or been read) the information provided above 
and agree to participate in this study. You will receive a copy of this signed consent form. 
 
 
Name of Proband Child (printed) 
 
 
Signature of Parent or Legally Authorized Representative 
Date 
 
 
 
Mother/Father/Caregiver 
Name of Parent Participant (printed) 
Relationship 
 
 
Signature of Parent Participant 
Date 
 
Mother/Father/Caregiver 
Name of Parent Participant (printed) 
Relationship 
 
 
Signature of Parent Participant 
Date 
 
 
 
 
Signature of Person Obtaining Consent 
Date 
 
In this research study, one consent form may be used to waive consent for the infant and capture 
informed consent of both parents; however, a separate HIPPA Authorization form will be completed 
for each participant. 
 
 
Waiver of Assent 
 
The assent of   
 
 
(name of child/minor) was waived because of: 
Age  
 
Maturity  
 
 Psychological state of the child  
 

Page 13 of 15 
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University of Alabama at Birmingham 
AUTHORIZATION FOR USE/DISCLOSURE OF PROTECTED HEALTH INFORMATION (PHI) FOR RESEARCH 
Participant Name:  
 
UAB IRB Protocol Number: IRB-300000328 
Research Protocol: South-seq: DNA sequencing for newborn 
Principal Investigator: Bruce Korf MD, PhD 
nurseries in the South 
Sponsor: NIH/NHGRI 
 
What is the purpose of this form? You are being asked to sign this form so that UAB may use and release your protected 
health information for research. Participation in research is voluntary. If you choose to participate in the research, you 
must sign this form so that your protected health information may be used for the research. 
 
Why do the researchers want my protected health information? The researchers want to use your protected health 
information as part of the research protocol listed above and as described to you in the informed consent. 
 
What protected health information do the researchers want to use? All medical information, including but not limited 
to information and/or records of any diagnosis or treatment of disease or condition, which may include sexually 
transmitted diseases (e.g., HIV, etc.) or communicable diseases, drug/alcohol dependency, etc.; all personal identifiers, 
including but not limited to your name, social security number, medical record number, date of birth, dates of service, 
etc.; any past, present, and future history, examinations, laboratory results, imaging studies and reports and treatments 
of whatever kind, including but not limited to drug/alcohol treatment, psychiatric/psychological treatment; 
financial/billing information, including but not limited to copies of your medical bills, and any other information related 
to or collected for use in the research protocol, regardless of whether the information was collected for research or non- 
research (e.g., treatment) purposes. 
 
Who will disclose, use and/or receive my protected health information? All Individuals/entities listed in the informed 
consent documents, including but not limited to, the physicians, nurses and staff and others performing services related 
to the research (whether at UAB or elsewhere); other operating units of UAB, HSF, UAB Highlands, Children’s of Alabama, 
Eye Foundation Hospital, and the Jefferson County Department of Health, as necessary for their operations; the IRB and 
its staff; the sponsor of the research and its employees and agents, including any CRO; and any outside regulatory 
agencies, such as the Food and Drug Administration, providing oversight or performing other legal and/or regulatory 
functions for which access to participant information is required. 
 
How will my protected health information be protected once it is given to others? Your protected health information 
that is given to the study sponsor will remain private to the extent possible, even though the study sponsor is not required 
to follow the federal privacy laws. However, once your information is given to other organizations that are not required to 
follow federal privacy laws, we cannot assure that the information will remain protected. 
 
How long will this Authorization last? Your authorization for the uses and disclosures described in this Authorization 
does not have an expiration date. 
 
Can I cancel this Authorization? You may cancel this Authorization at any time by notifying the Principal Investigator, in 
writing, referencing the research protocol and IRB Protocol Number. If you cancel this Authorization, the study doctor and 
staff will not use any new health information for research. However, researchers may continue to use the protected 
health information that was provided before you cancelled your authorization. 
 
Can I see my protected health information? You have a right to request to see your protected health information. 
However, to ensure the scientific integrity of the research, you will not be able to review the research information until 
after the research protocol has been completed. 
 
Signature of participant:  
 
Date:  
 
or participant's legally authorized representative:  
 
Date:  
 
Printed Name of participant’s representative:  
 
Relationship to the participant:  
 

University of Alabama at Birmingham 
AUTHORIZATION FOR USE/DISCLOSURE OF PROTECTED HEALTH INFORMATION (PHI) FOR RESEARCH 
Participant Name:  
 
UAB IRB Protocol Number: IRB-300000328 
Research Protocol: South-seq: DNA sequencing for newborn 
Principal Investigator: Bruce Korf MD, PhD 
nurseries in the South 
Sponsor: NIH/NHGRI 
 
What is the purpose of this form? You are being asked to sign this form so that UAB may use and release your protected 
health information for research. Participation in research is voluntary. If you choose to participate in the research, you 
must sign this form so that your protected health information may be used for the research. 
 
Why do the researchers want my protected health information? The researchers want to use your protected health 
information as part of the research protocol listed above and as described to you in the informed consent. 
 
What protected health information do the researchers want to use? All medical information, including but not limited 
to information and/or records of any diagnosis or treatment of disease or condition, which may include sexually 
transmitted diseases (e.g., HIV, etc.) or communicable diseases, drug/alcohol dependency, etc.; all personal identifiers, 
including but not limited to your name, social security number, medical record number, date of birth, dates of service, 
etc.; any past, present, and future history, examinations, laboratory results, imaging studies and reports and treatments 
of whatever kind, including but not limited to drug/alcohol treatment, psychiatric/psychological treatment; 
financial/billing information, including but not limited to copies of your medical bills, and any other information related 
to or collected for use in the research protocol, regardless of whether the information was collected for research or non- 
research (e.g., treatment) purposes. 
 
Who will disclose, use and/or receive my protected health information? All Individuals/entities listed in the informed 
consent documents, including but not limited to, the physicians, nurses and staff and others performing services related 
to the research (whether at UAB or elsewhere); other operating units of UAB, HSF, UAB Highlands, Children’s of Alabama, 
Eye Foundation Hospital, and the Jefferson County Department of Health, as necessary for their operations; the IRB and 
its staff; the sponsor of the research and its employees and agents, including any CRO; and any outside regulatory 
agencies, such as the Food and Drug Administration, providing oversight or performing other legal and/or regulatory 
functions for which access to participant information is required. 
 
How will my protected health information be protected once it is given to others? Your protected health information 
that is given to the study sponsor will remain private to the extent possible, even though the study sponsor is not required 
to follow the federal privacy laws. However, once your information is given to other organizations that are not required to 
follow federal privacy laws, we cannot assure that the information will remain protected. 
 
How long will this Authorization last? Your authorization for the uses and disclosures described in this Authorization 
does not have an expiration date. 
 
Can I cancel this Authorization? You may cancel this Authorization at any time by notifying the Principal Investigator, in 
writing, referencing the research protocol and IRB Protocol Number. If you cancel this Authorization, the study doctor and 
staff will not use any new health information for research. However, researchers may continue to use the protected 
health information that was provided before you cancelled your authorization. 
 
Can I see my protected health information? You have a right to request to see your protected health information. 
However, to ensure the scientific integrity of the research, you will not be able to review the research information until 
after the research protocol has been completed. 
 
Signature of participant:  
 
Date:  
 
or participant's legally authorized representative:  
 
Date:  
 
Printed Name of participant’s representative:  
 
Relationship to the participant:  
 
 
Page 14 of 15 
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Page 15 of 15 
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University of Alabama at Birmingham 
AUTHORIZATION FOR USE/DISCLOSURE OF PROTECTED HEALTH INFORMATION (PHI) FOR RESEARCH 
Participant Name:  
 
UAB IRB Protocol Number: IRB-300000328 
Research Protocol: South-seq: DNA sequencing for newborn 
Principal Investigator: Bruce Korf MD, PhD 
nurseries in the South 
Sponsor: NIH/NHGRI 
 
What is the purpose of this form? You are being asked to sign this form so that UAB may use and release your protected 
health information for research. Participation in research is voluntary. If you choose to participate in the research, you 
must sign this form so that your protected health information may be used for the research. 
 
Why do the researchers want my protected health information? The researchers want to use your protected health 
information as part of the research protocol listed above and as described to you in the informed consent. 
 
What protected health information do the researchers want to use? All medical information, including but not limited 
to information and/or records of any diagnosis or treatment of disease or condition, which may include sexually 
transmitted diseases (e.g., HIV, etc.) or communicable diseases, drug/alcohol dependency, etc.; all personal identifiers, 
including but not limited to your name, social security number, medical record number, date of birth, dates of service, 
etc.; any past, present, and future history, examinations, laboratory results, imaging studies and reports and treatments 
of whatever kind, including but not limited to drug/alcohol treatment, psychiatric/psychological treatment; 
financial/billing information, including but not limited to copies of your medical bills, and any other information related 
to or collected for use in the research protocol, regardless of whether the information was collected for research or non- 
research (e.g., treatment) purposes. 
 
Who will disclose, use and/or receive my protected health information? All Individuals/entities listed in the informed 
consent documents, including but not limited to, the physicians, nurses and staff and others performing services related 
to the research (whether at UAB or elsewhere); other operating units of UAB, HSF, UAB Highlands, Children’s of Alabama, 
Eye Foundation Hospital, and the Jefferson County Department of Health, as necessary for their operations; the IRB and 
its staff; the sponsor of the research and its employees and agents, including any CRO; and any outside regulatory 
agencies, such as the Food and Drug Administration, providing oversight or performing other legal and/or regulatory 
functions for which access to participant information is required. 
 
How will my protected health information be protected once it is given to others? Your protected health information 
that is given to the study sponsor will remain private to the extent possible, even though the study sponsor is not required 
to follow the federal privacy laws. However, once your information is given to other organizations that are not required to 
follow federal privacy laws, we cannot assure that the information will remain protected. 
 
How long will this Authorization last? Your authorization for the uses and disclosures described in this Authorization 
does not have an expiration date. 
 
Can I cancel this Authorization? You may cancel this Authorization at any time by notifying the Principal Investigator, in 
writing, referencing the research protocol and IRB Protocol Number. If you cancel this Authorization, the study doctor and 
staff will not use any new health information for research. However, researchers may continue to use the protected 
health information that was provided before you cancelled your authorization. 
 
Can I see my protected health information? You have a right to request to see your protected health information. 
However, to ensure the scientific integrity of the research, you will not be able to review the research information until 
after the research protocol has been completed. 
 
Signature of participant:  
 
Date:  
 
or participant's legally authorized representative:  
 
Date:  
 
Printed Name of participant’s representative:  
 
Relationship to the participant:  
 

Page 1 of 13 
Version Date: 02/14/2020 
 
 
 
 
CONSENT FORM 
Title of Research: 
South-seq: DNA sequencing for newborn nurseries in the South 
(NIH Grant Number 2U01HG007301-05) 
Site: 
University of Mississippi Medical Center 
UAB IRB Protocol #: 
IRB-300000328 
 
Principal Investigators: 
Renate Savich, MD and Brian Kirmse, MD 
 
Sponsor: 
NIH National Human Genome Research Institute 
(Contact: Lucia Hindorff PhD, MPH) 
UAB IRB 
Approved 
04-Mar-2020 
until 
27-Aug-2020 
 
 
Purpose of the Research 
We are asking you to take part in a research study. The purpose of this research study is to use 
whole genome sequencing (WGS), looking at your DNA, to identify the genetic cause of conditions 
like those observed in your child. For individuals with rare, undiagnosed diseases and their families, 
this experimental genetic test may provide information about what is causing the disease or 
condition. This information may be beneficial to your family in directing your child’s health care, 
medical treatments, and your family planning decisions. Educational tools about your child’s 
condition may also become available with a confirmed genetic diagnosis. 
 
In addition, due to the limited number of genetic counselors available to support patients that may 
benefit from WGS, we will be comparing two results delivery methods: genetic counselors (standard 
of care), and healthcare providers (e.g. neonatologists and neonatology nurse practitioners) who 
undergo specific genetics results delivery training. In this clinical trial, we aim to demonstrate that 
both delivery methods are equivalent (i.e. there is no difference between the two methods). In 
order to so this, we plan to record the return of results conversations that you will have as part of 
this study. 
Due to the experimental nature of this research study, data generated is based upon the knowledge 
currently accepted in the field. As more genomes are sequenced and as sequencing techniques 
improve, we will be better at identifying and understanding extremely rare variants (rare changes in 
DNA). In doing this, we will also improve and we will learn more about how certain variants may 
cause disease. For this reason, we plan to store samples for future research. 
There will be approx. 1500 newborn participants enrolled for WGS, and 800 parents and caregivers 
enrolled for the clinical trial across 6 NICU sites: UAB, Children’s of Alabama, University of Mississippi 
Medical Center (UMMC), Woman’s Hospital, University of Louisville and Norton Healthcare (UofL). 
Samples will also be collected from biological mothers and fathers (up to 2,250 individuals), when 
For Children (persons under 18 years of age) participating in this study, the term “You” addresses both 
the participant ("you") and the parent or legally authorized representative ("your child"). 

Page 2 of 13 
Version Date: 02/14/2020 
 
available, so that we can use their samples to determine inheritance of any variants we find in their 
child. We also hope to include a diverse group of participants so we are planning to offer this test to 
all populations, especially those underrepresented in science and genomic research such as African 
Americans and those from rural areas. 
Explanation of Procedures 
If you agree to join the study, you are agreeing to: 
● Give us permission to collect a blood sample for DNA analysis 
o Adults will give approximately 8mL (approx. 1.6 tsp) of blood that will be drawn from 
the arm. 
o Newborns will give no more than the maximum amount allowed for their body weight 
according to the Children’s of Alabama guidelines. 
● Give us permission to fully analyze your DNA (or other related material, like RNA or 
protein) and determine the health significance of your genetic results. 
● Allow us to return health information to you that we feel may be important to your child’s 
health or other biological relatives. 
● Allow key study personnel to access your child’s personal medical records to aid in analysis. 
Study personnel may collect information about the child’s symptoms, health history, 
medications/treatments, etc. 
● Provide key study personnel with information about your child’s health history, pregnancy and 
birth history, information about your health and that of other family members, if you know it, 
etc. Study personnel will not access your medical record. They will only have access to the 
information that you choose to share with them. 
● Allow us, if you so choose, to return genetic results that are not related to your child’s 
condition but are medically important for other reasons. 
● Answer survey questions at 5 time points: the time of consent, return of results (ROR) 
appointment, 1-month post-ROR, 4-months post-ROR, and 4.5-months post-ROR. Each survey 
will take approximately 20-35 minutes to complete. 
You will be asked to take part in two clinic visits here in the nursery or at the outpatient clinic. 
During the first visit, you will be asked to enroll in the study and give a blood sample (1.5hrs) and 
during the second visit you will receive the results of your child’s DNA test either by a genetic 
counselor or a trained healthcare provider (1.5-2hrs). The return of results visit can either take 
place in-person or over the phone. A certified letter with results will be sent to those who do not 
participate in either in the in-person or phone ROR appointment. 
 
More than one parent/guardian/caregiver of a child receiving WGS can participate in the study. It is 
important that anyone participating in the survey portion of the study be present at ROR and 
complete every survey. 
 
Collecting samples from both biological parents increases the chances of identifying genetic 
variation in your child that might be causing his or her symptoms. However, if both parents are 
not available, we can still analyze eligible patients and potentially find valuable information. In 
cases where we enroll family members, our DNA test can identify whether a person is the 

Page 3 of 13 
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biological parent or not. We will not tell you or your family members if we find out that one or 
both parents are not biologically related to the child, however we are less likely to discover 
diagnostic information about your condition without both biological parents. 
Your blood samples will be labeled with a unique code (coded) and sent to researchers at the 
HudsonAlpha Institute for Biotechnology, a non-profit genetics research center located in 
Huntsville, AL. Some relevant, health information will also be given to the research staff, and 
coded with a unique study identifier, to aid in their analysis. 
 
We will use state-of-the-art technologies to generate large amounts of information about the DNA 
from you and your child. A group of experts, including medical doctors and researchers, will use 
scientific findings and genetic databases to help decide what genetic information may be 
important to the health of your child. The sequence of all results believed to be medically relevant 
or important to your child’s or your own health will be validated at HudsonAlpha Clinical Services 
Laboratory in Huntsville, AL or another independent clinical laboratory. We expect the entire DNA 
analysis process to take 2-4 months. 
 
We do intend to perform analysis of each sample within our budgetary and technical means. If we 
are unable to analyze your samples you will be notified within 6 months of enrollment and sample 
collection. There is no cause for concern if you are told that we could not complete the analysis 
and provide you with results. 
 
Return of results is at the discretion of the clinicians and researchers involved with this study. If 
they identify results that may impact your child’s health, they may return those results to you. You 
will be scheduled for an appointment to discuss these findings with a genetic counselor or a 
trained healthcare provider. Only a subset of results believed to be important to your child’s 
medical care or those in line with the goals of this study will be reported to you. We will not 
provide you with all of the genetic information that we generate. At your results appointment, 
you may be provided with information regarding: 
● Primary findings - These findings will include information about a variant(s) (DNA change) 
that may potentially be the reason for your child’s phenotype (symptoms) or condition. 
o Most children will not receive a primary finding (or diagnosis). If no diagnosis is 
found, we will tell you. Even if we do not find a genetic diagnosis, your condition 
may still be the result of a change in your DNA that we are currently unable to 
identify. 
o If you receive a genetic diagnosis, this may not change your child’s prognosis or 
medical treatment. However, it may help you and your doctor to better understand 
the cause of your child’s condition and the risks of similar conditions affecting your 
biological children. 
● Secondary findings – These findings may be reported to any study participant and may 
include any genetic changes that might impact your health or the health of your current or 
future children. These may include: 

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o Whether there are any changes in your DNA that could put you at a higher risk for 
developing a disease unrelated to your child’s condition in the future, such as cancer 
or heart disease. 
1. Some of these diseases may be medically useful and some may not be 
medically useful. We will not return results that are not medically useful. 
2. Some of these diseases will appear in childhood and others will appear 
when you are an adult. 
● Carrier status – In the event that we discover that your child’s symptoms are caused by a 
recessive genetic condition where he or she inherited one variant (DNA change) from each 
parent, we may provide information about whether or not you are a "carrier" for a genetic 
change that may be passed on to your biological children. 
We will arrange for a genetic counselor or a trained healthcare provider to discuss the results of 
the test with you. Educational materials will also be made available to you to help you better 
understand any results that you may or may not receive as part of this study. 
You will be actively enrolled in this study for up to one year however we may continue to access 
your medical record for up to 5 years. We plan to use coded information from our medical record 
to determine the impact of whole genome sequencing and genetic diagnosis on medical care. 
After you receive the results of the genetic test, you may be contacted by your physician or key 
study personnel to check on you or to ask follow-up questions. Your DNA samples may be stored 
indefinitely for future research unless you choose to withdraw from the study. Please note that 
participation in this study is voluntary and you may withdraw from this study at any time. 
 
You will also be presented with a baseline survey at the time of enrollment that you can complete 
online using Genome Gateway. The survey will ask you questions about basic demographics, how 
you feel about your child’s health and your experience in the hospital, how well you understand 
medical terms, math and genetics. After you receive results, you will be asked some of these same 
questions and some additional ones related to your health, your understanding of the genetics 
results returned, and how the results influence future planning at 1-month post-ROR, 4-months 
post-ROR, and 4.5-months post-ROR. 
 
Risks and Discomforts 
The risks of drawing blood include pain, bruising, lightheadedness, and fainting. Infection at the site 
of the needle stick is a rare side effect. These are the same risks you face any time you have a blood 
test. 
 
The main concerns associated with genetic testing are anxiety, depression, or other forms of 
emotional distress that may result from receiving genetic information about the suspected cause of 
your child’s condition. This is especially true for those diseases that are not treatable or preventable. 
Though some treatments have been shown to help individuals with certain genetic conditions, there 
is no "cure" for most. 

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When performing genetic testing, it may be discovered that family relationships are not as predicted. 
For example, a child might not be biologically related to his/her father, or two people who are 
married might turn out to be biologically related. These findings will not be disclosed as part of this 
study. 
In some cases, you may receive information about your carrier status and/or changes in your DNA 
that may impact your health. These findings will only be returned if they were inherited by your child 
who is enrolled in this study and suspected to contribute to their condition. Genetic changes in 
children that affect development may be inherited from one or both parents, even if the parents 
appear to be healthy. This information may affect the way you view or evaluate yourself or your 
family. It may also influence, or generate anxiety about, future family planning decisions. 
It is also important to keep in mind that you and your biological relatives have similar DNA 
sequences. This means that genetic information about your child may also have implications for your 
relatives if the variation was inherited. 
You may be referred to an additional physician or clinic for further testing or advice depending on 
the type of genetic information we generate from your sample. If you experience psychological 
distress or other difficulties, we can also refer you to an appropriate resource for care and/or 
support. 
 
There may be unforeseeable risks associated with receiving genetic information and the potential 
decisions, actions, or inactions that may be required in response to that information. Please consider 
this carefully and ask any questions that you may have before deciding whether or not to participate 
in this study. 
 
It is important that you consider the risks and uncertainties of this research study that make it 
different from traditional medical testing. 
 
We will make sure that the information that you are given is as accurate as possible to the best of 
our ability. We will use the best standards, practices, and technologies available to researchers. 
However, the technologies available to analyze DNA and our knowledge of how DNA affects health 
are changing rapidly. They are also subject to much uncertainty. Some DNA changes that are 
important to health may be missed, and other DNA changes that are not important may be 
incorrectly identified as if they are important. There are also moral and ethical questions about using 
genetic information on which scientific and medical communities have not yet reached a consensus. 
Therefore, we do NOT guarantee that our test will have the same levels of completeness, accuracy, 
or standardization associated with more traditional medical tests. 

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Before offering your consent to participate in this research study, please consider all of the risks 
associated with: 
● The return or possible lack of return of results; 
● Whether our interpretation of those results is accurate; 
● How you and/or your family will choose to act upon or not act upon the information or lack 
of information. 
Benefits 
You may not benefit directly from taking part in this study. However, your participation may lead to 
new discoveries that help to advance medical research and improve patient care, especially, but not 
only, newborn patient care in the future. Your participation in this study may help to make health 
care and access to health care broader and more representative. 
You may find out if there is a change in your child’s DNA that has altered their development. You 
might also find out if this change could affect future biological children. 
A genetic diagnosis may help you connect with other families in the community who face similar 
medical problems. While unlikely, it is possible that a genetic diagnosis may point your doctor to a 
better medical and/or educational treatment. 
 
You may discover that you or your child are at an increased risk for developing other diseases and 
that information may be of medical benefit. 
 
None of the above benefits are guaranteed, and it is expected that many participants will not receive 
specific information that is relevant to their health. 
 
Alternatives 
This is not a treatment study. Your alternative is not to participate in this research study. 
 
Confidentiality 
Every effort will be made to keep the information we learn about you private. Study personnel, the 
Food and Drug Administration (FDA), the NIH National Human Genome Research Institute (NHGRI), 
the Office for Human Research Protections (OHRP), and the University of Mississippi Medical Center’s 
Institutional Review Board (IRB) and Office of Integrity and Compliance, Grants and Contracts and the 
UAB (University of Alabama at Birmingham) Institutional Review Board (IRB) may review the study 
records. If study results are published your name will not be used. 
 
The information from the research including your child’s clinical information, family history, and 
genetic variants may be published for scientific purposes; however, your identity will not be given out 
to anyone outside of the clinical team involved with the study. 
 
Although every effort will be made to keep your information confidential, hospital staff and health 
professionals are required to report suspected abuse or neglect of children, elderly and disabled 

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persons, reportable communicable diseases and/or possible threat of harm to self or others to 
appropriate state agencies. 
If this research involves your child’s care, diagnosis, or treatment a copy of this research Informed 
Consent Document will be included in your child’s health record. Individuals involved in your child’s 
treatment; who obtain information for payment of services; or who access information for health 
care operations may have access to your child’s research records. 
This may include either a paper medical record or electronic medical record (EMR). An EMR is an 
electronic version of a paper medical record of your care within this health system. Your child’s EMR 
may indicate that you and your child are enrolled in this study and provide the name and contact 
information for the principal investigator. 
This study has a Certificate of Confidentiality from the National Institutes of Health which will help us 
protect the privacy of our research participants. The Certificate is intended to protect against the 
involuntary release of participant information collected during this study. 
The Certificate does not prevent you or a member of your family from voluntarily releasing 
information about yourself or your involvement in this research. If an insurer, medical care provider 
or other person gets your written authorization to receive research information UMMC will not use 
the Certificate to withhold that information. 
 
The Certificate will not protect against mandatory reporting by the researchers to local, state or 
federal agencies of information on suspected child abuse, reportable communicable diseases and/or 
possible threat of harm to self or others. 
 
Results of research tests or procedures that have been clinically validated (i.e. Sanger reports) may be 
placed in your child’s medical record. All information within your child’s medical record can be 
viewed by individuals authorized to access the record. 
 
Information relating to this study, including your name, your child’s medical record number, date of 
birth and social security number, may be shared with the billing offices of UMMC so costs for clinical 
services can be appropriately paid for by either the study account or by your insurance. 
 
A federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes it illegal 
for health insurance companies, group health plans, and some employers to discriminate against you 
based on your genetic information. This law generally will protect you in the following ways: 
● Health insurance companies and group health plans may not request your genetic information 
that we get from this research. 
● Health insurance companies and group health plans may not use your genetic information 
when making decisions regarding your eligibility or premiums. 
● Employers with 15 or more employees may not use your genetic information that we get from 
this research when making a decision to hire, promote, or fire you or when setting the terms 
of your employment. 

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Be aware this federal law does not protect you against genetic discrimination by companies that sell 
life insurance, disability insurance, or long-term care insurance, nor does it protect you against 
genetic discrimination by some employers. 
 
Protected Health Information 
Protected health information is any personal health information through which your child can be 
identified. The data collected in this study includes: your child’s name; date of birth; zip code; the 
history and diagnosis of your child’s disease; current and previous treatments your child has received; 
other medical conditions that may affect your child’s treatment; laboratory, radiology and pathology 
test results; and follow-up information about your child’s general health, the status of your child’s 
disease and late effects from treatment. 
 
By signing this permission document, you authorize the study doctors at the University of Mississippi 
Medical Center and their study staff to collect this information and use your child’s records as 
necessary for this study. 
 
The HudsonAlpha, the University of Alabama at Birmingham, Woman’s Hospital and the University of 
Mississippi Medical Center will use your information to determine the effectiveness of this study. 
Your child’s medical information and records, once disclosed, may be re-disclosed by any of the 
recipients identified above and may no longer be protected by the Privacy Standards of the Health 
Insurance Portability and Accountability Act (HIPAA), which is a federal regulation designed to protect 
medical information, including medical information and records created through research. 
 
You have the right to cancel this authorization at any time by providing one of the study doctors with 
a written request to cancel the authorization. If you cancel this authorization medical information 
and records about your child that were created before the authorization was cancelled will still be 
used and disclosed as needed to preserve the integrity of the study. 
 
This authorization has no expiration date. If you do not sign this consent document, you and your 
child will not be allowed to participate in this study. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web site 
will include a summary of the results. You can search this Web site at any time. 
Voluntary Participation and Withdrawal 
Whether or not you take part in this study is your choice. There will be no penalty if you decide not to 
be in the study. If you decide not to be in the study, you will not lose any benefits you are otherwise 
owed. You are free to withdraw from this research study at any time. Your choice to leave the study 
will not affect your relationship with any institution participating in this study. 
In the event that you chose to withdraw from the study: 
● No further genetic information from the study will be reported to you. 
● Your blood samples will be destroyed. 

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● You will not be contacted to provide new information, additional samples, or 
● participate in additional studies related to this project. 
● If the analysis of your DNA has been completed, this information will be retained for the 
study. 
If you would like to withdraw from the study, please contact Dr. Renate Savich at 601-815-7158 or 
Dr. Brian Kirmse at 601-984-1900. 
Cost of Participation 
There will be no cost to you for taking part in this study. The blood draw, genomic sequencing and 
analysis, and genetic counseling related to this study will be provided to you at no cost during the 
study period. 
After you receive your research results, you may decide with your doctor or your child’s doctor to 
get more testing. The costs of your standard medical care or any services rendered in response to a 
genetic finding identified by this research project will be billed to you and/or your insurance 
company in the usual manner. This type of follow-up medical testing will be considered part of your 
clinical care and will not be paid for by the research study. 
 
Payment for Participation in Research 
Participation in this study is voluntary and $25 will be provided for each survey completed for a total 
of $125 for your completion of all 5 study-related surveys. Ask the study staff about the method of 
payment that will be used for this study (e.g., check, cash, gift card, direct deposit); payment may 
take up to 4 weeks to process. 
 
Payment for Research-Related Injuries 
 
In the case of injury or illness resulting from your direct participation in this study, medical treatment 
is available to you at the University of Mississippi Medical Center. You will be charged the usual and 
customary charges for any such treatment you receive. 
 
UAB, UMMC, HudsonAlpha, and NIH/NHGRI/sponsors of this research project have not provided for 
any payment if you are harmed as a result of taking part in this study. If such harm occurs, treatment 
will be provided. However, this treatment will not be provided free of charge. 
 
Significant New Findings 
The study doctor or study staff will tell you if new information becomes available that might affect 
your choice to stay in the study. Please note that HudsonAlpha may, but is not required to, reanalyze 
your sample or report any new findings after results have been returned. 
 
Storage of Specimens for Future Use 
As part of this study, we would like to store some of the blood and DNA specimens collected from 
you and your child for validation of variants (to determine if a variant was inherited from a parent, 
etc.) identified by this project and for future research relevant to rare disease or other genetic 

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disorders. The future research may be conducted by the study doctor or by other researchers that 
obtain IRB approval for their research. The specimens will be labeled with a code that only the study 
doctor can link back to you. Results of any future research will not be given to you or your doctor. The 
specimens obtained from you in this research may help in the development of a future commercial 
product. There are no plans to provide financial compensation to you should this occur. You do not 
have to agree to allow your specimens to be stored in order to be part of this study. 
You may at any time withdraw from the study and request that your specimens be removed from 
storage and not be used for future research. If you decide you want your specimens removed, you 
may contact Dr. Bruce Korf at 205-934-9411. Once the request is received, and if your samples have 
not already been used for other research, they will be destroyed. If you do not make such a request, 
your specimens will be stored indefinitely or until used. 
Initial next to your choice below: 
 
I agree to allow my specimens to be kept in the HudsonAlpha CSL and used for future genetics 
research. 
 
 
I do NOT agree to allow my specimens to be kept and used for future research. 
 
Genomic Data Sharing (GDS) 
We consider the privacy of you and your child’s information to be of high priority and will take a 
variety of steps to ensure that privacy. However, it is important for researchers to share some of the 
information that they learn from studying human samples. We will never share personally 
identifiable information, like names and addresses, with anyone outside of the research study. 
However, parts of you and your child’s information may be shared. 
 
Some of you and your child’s genetic information, limited to a very small subset that will not cause 
privacy loss risks to you, may be published in scientific journals or other unrestricted-access public 
venues to encourage sharing of the knowledge that may be learned by analyzing your DNA and DNA 
from other individuals. This could include information about your child’s symptoms, their age, and 
any genetic findings that we discover. 
 
We may share coded lists of the DNA differences that we identify in public genetic databases. These 
databases gather genetic information from large groups of people and are pooled together such that 
no specific participant can be identified. 
 
There is a very small chance that some commercial value may result from the use of you and your 
child’s donated samples or genetic information. If that happens, you will not receive a share in any 
profits. 
 
Unless you opt out, we may submit you and your child’s complete genomic data along with some of 
your child’s coded health information to an NIH-designated Data Repository such as dbGAP 
(http://www.ncbi.nlm.nih.gov/gap), AnVIL (https://anvilproject.org/), or another controlled access 

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database. Access to dbGAP and AnVIL is only available to qualified researchers at qualified 
institutions who have agreed to abide by certain privacy safeguards, obligating them, both legally 
and ethically, to protect you and your child’s privacy and to maintain information confidentiality. 
However, since your genetic information is unique to you, there is a small chance that someone 
could trace your information back to you and your child. This risk is very small, but may grow in the 
future. Some risks and benefits are listed below: 
Risks: The risk of sharing your genomic data is that someone could link the information stored 
in the databases back to you and your child. If your information suggests something about 
your health such as increased risk for disease, it could be misused. For example, it could be 
used to make it harder for you to get or keep a job or insurance or be used to discriminate 
against you or your family. There may also be other unknown risks. As stated above 
(confidentiality section of this form), there are federal protections against the misuse of your 
data (i.e. the Genetic Information Nondiscrimination Act, GINA). 
Benefits: There is no direct benefit to you and your child from sharing your genomic data with 
NIH-designated repositories, however allowing researchers to use your data may lead to a 
better understanding of how genes affect health which may help other people in the future. 
 
Initial next to your choice below: 
 
 
 I agree for my and my child’s genetic and other relevant study data, such as health information, 
to be shared with NIH-designated repositories such as dbGAP and AnVIL in a coded form for 
future research or analysis 
 
 I do NOT agree for my and my child’s genetic and other relevant study data, such as health 
information, to be shared with NIH-designated repositories such as dbGAP and AnVIL in a 
coded form for future research or analysis 
 
Contact for Future Research 
As new research opportunities are identified, the researchers may wish to perform additional tests 
on fresh samples or invite eligible participants to enroll in new studies. We would like permission to 
contact you in the future, however this is not a requirement to participate in this study. A separate 
consent form will be obtained if you wish to participate in future research. 
 
Initial next to your choice below: 
 
 
 You have permission to contact me about new research opportunities that may interest me. 
 
 
 
You do NOT have permission to contact me about new research opportunities. 
 
Secondary Findings 
One unanimous decision to receive or not to receive secondary findings must be made by each 
participant family. Because parental samples are only used for confirmation of variation identified in 

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the child’s whole genome sequence for this project, only those secondary findings identified in the 
child will be confirmed in the parental samples. Participant families may opt to receive this 
information, if available. If a family chooses to do so, information about an identified secondary 
finding will be included in the child’s medical record. Nothing will be placed in the parent’s medical 
record. 
Initial next to your choice below: 
 
 
 We (child and parent(s), if enrolled) would like to receive information about secondary 
findings. 
 
 
 We (child and parent(s), if enrolled) would NOT like to receive information about secondary 
findings. 
 
Questions 
If you have any questions, concerns, or complaints about the research or a research-related injury 
including available treatments, please contact Dr. Renate Savich at 601-815-7158or Dr. Brian Kirmse 
at 601-984-1900 or Dr. Bruce Korf (205-934-9411) at UAB. 
 
If you have questions about your rights as a research participant, or concerns or complaints about the 
research, you may contact the UAB Office of the IRB (OIRB) at (205) 934-3789 or toll free at 1-855- 
860-3789. Regular hours for the OIRB are 8:00 a.m. to 5:00 p.m. CT, Monday through Friday. 
 
You may also discuss your rights as a research participant with the Chairman of the University of 
Mississippi Medical Center's Institutional Review Board, 2500 North State Street, Jackson, Mississippi 
39216; telephone 601 984-2815; facsimile 601 984-2961 or via email, UMCIRB@umc.edu 
 
Statement of Participation 
 
I have been told about this study and the possible risks and benefits. I agree for my child to 
participate in this study, to follow instructions, and to report any side effects to my child's study 
doctor. My child's participation is voluntary and my child may withdraw at any time without any 
penalty or loss of benefits to which he/she is entitled, including medical care at the University of 
Mississippi Medical Center. 
 
By signing this form, I am not giving up any legal rights I or my child may have. 

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Signatures 
Your signature below indicates that you have read (or been read) the information 
provided above and agree to have your child participate in this study. You will receive a copy of this signed consent form. 
Your signature below indicates that you have read (or been read) the information provided above and agree to participate 
in this study. You will receive a copy of this signed consent form. 
 
Name of Proband Child (printed) 
Signature of Parent or Legally Authorized Representative 
Date 
Mother/Father/Caregiver 
Name of Parent Participant (printed) 
Relationship 
 
Signature of Parent Participant 
Date 
 
Mother/Father/Caregiver 
Name of Parent Participant (printed) 
Relationship 
 
Signature of Parent Participant 
Date 
 
Printed Name of Person Obtaining Consent 
Date 
 
 
Signature of Person Obtaining Consent 
Date 
 
Signature of Minor Mother 
Date 
 
Name of Minor Mother (printed) 
Signature of Minor Mother’s Parent/Guardian 
Date 
Mother/Father/Caregiver 
Name of Minor Mother’s Parent/Guardian (printed) 
Relationship 
 
I acknowledge that the participant identified above has been entered into this study, with properly obtained informed 
consent. 
 
Signature of Investigator 
Date 
 
In this research study, one consent form may be used to waive consent for the infant and capture informed consent of 
both parents; however, a separate HIPAA Authorization form will be completed for each participant. 

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CONSENT FORM 
Title of Research: 
South-seq: DNA sequencing for newborn nurseries in the South 
(NIH Grant Number 2U01HG007301-05) 
Site: 
Woman’s Hospital, Baton Rouge, Louisiana 
UAB IRB Protocol #: 
IRB-300000328 
 
Principal Investigators: 
Steven Spedale, MD 
 
Sponsor: 
NIH National Human Genome Research Institute 
(Contact: Lucia Hindorff PhD, MPH) 
UAB IRB 
Approved 
04-Mar-2020 
until 
27-Aug-2020 
 
 
Purpose of the Research 
We are asking you to take part in a research study. The purpose of this research study is to use 
whole genome sequencing (WGS), looking at your DNA, to identify the genetic cause of conditions 
like those observed in your child. For individuals with rare, undiagnosed diseases and their families, 
this experimental genetic test may provide information about what is causing the disease or 
condition. This information may be beneficial to your family in directing your child’s health care, 
medical treatments, and your family planning decisions. Educational tools about your child’s 
condition may also become available with a confirmed genetic diagnosis. 
 
In addition, due to the limited number of genetic counselors available to support patients that may 
benefit from WGS, we will be comparing two results delivery methods: genetic counselors (standard 
of care), and healthcare providers (e.g. neonatologists and neonatology nurse practitioners) who 
undergo specific genetics results delivery training. In this clinical trial, we aim to demonstrate that 
both delivery methods are equivalent (i.e. there is no difference between the two methods). In 
order to so this, we plan to record the return of results conversations that you will have as part of 
this study. 
Due to the experimental nature of this research study, data generated is based upon the knowledge 
currently accepted in the field. As more genomes are sequenced and as sequencing techniques 
improve, we will be better at identifying and understanding extremely rare variants (rare changes in 
DNA). In doing this, we will also improve and we will learn more about how certain variants may 
cause disease. For this reason, we plan to store samples for future research. 
There will be approx. 1500 newborn participants enrolled for WGS, and 800 parents and caregivers 
enrolled for the clinical trial across 6 NICU sites: UAB, Children’s of Alabama, University of Mississippi 
Medical Center (UMMC), Woman’s Hospital, University of Louisville and Norton Healthcare (UofL). 
Samples will also be collected from biological mothers and fathers (up to 2,250 individuals), when 
For Children (persons under 18 years of age) participating in this study, the term “You” addresses both 
the participant ("you") and the parent or legally authorized representative ("your child"). 

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available, so that we can use their samples to determine inheritance of any variants we find in their 
child. We also hope to include a diverse group of participants so we are planning to offer this test to 
all populations, especially those underrepresented in science and genomic research such as African 
Americans and those from rural areas. 
 
Explanation of Procedures 
If you agree to join the study, you are agreeing to: 
● Give us permission to collect a blood sample for DNA analysis 
o Adults will give approximately 8mL (approx. 1.6 tsp) of blood that will be drawn from 
the arm. 
o Newborns will give no more than the maximum amount allowed for their body weight 
according to the Children’s Of Alabama guidelines. 
● Give us permission to fully analyze your DNA (or other related material, like RNA or 
protein) and determine the health significance of your genetic results. 
● Allow us to return health information to you that we feel may be important to your child’s 
health or other biological relatives. 
● Allow key study personnel to access your child’s personal medical records to aid in analysis. 
Study personnel may collect information about the child’s symptoms, health history, 
medications/treatments, etc. 
● Provide key study personnel with information about your child’s health history, pregnancy and 
birth history, information about your health and that of other family members, if you know it, 
etc. Study personnel will not access your medical record. They will only have access to the 
information that you choose to share with them. 
● Allow us, if you so choose, to return genetic results that are not related to your child’s 
condition but are medically important for other reasons. 
● Answer survey questions at 5 time points: the time of consent, return of results (ROR) 
appointment, 1-month post-ROR, 4-months post-ROR, and 4.5-months post-ROR. Each survey 
will take approximately 20-35 minutes to complete. 
 
You will be asked to take part in two clinic visits here in the nursery or at the outpatient clinic. 
During the first visit, you will be asked to enroll in the study and give a blood sample (1.5hrs) and 
during the second visit you will receive the results of your child’s DNA test either by a genetic 
counselor or a trained healthcare provider (1.5-2hrs). The return of results visit can either take 
place in-person or over the phone. A certified letter with results will be sent to those who do not 
participate in either in the in-person or phone ROR appointment. 
More than one parent/guardian/caregiver of a child receiving WGS can participate in the study. It is 
important that anyone participating in the survey portion of the study be present at ROR and 
complete every survey. 
Collecting samples from both biological parents increases the chances of identifying genetic 
variation in your child that might be causing his or her symptoms. However if both parents are not 
available, we can still analyze eligible patients and potentially find valuable information. In cases 
where we enroll family members, our DNA test can identify whether a person is the biological 

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parent or not. We will not tell you or your family members if we find out that one or both parents 
are not biologically related to the child, however we are less likely to discover diagnostic 
information about your condition without both biological parents. 
Your blood samples will be labeled with a unique code (coded) and sent to researchers at the 
HudsonAlpha Institute for Biotechnology, a non-profit genetics research center located in 
Huntsville, AL. Some relevant, health information will also be given to the research staff, and 
coded with a unique study identifier, to aid in their analysis. 
 
We will use state-of-the-art technologies to generate large amounts of information about the DNA 
from you and your child. A group of experts, including medical doctors and researchers, will use 
scientific findings and genetic databases to help decide what genetic information may be 
important to the health of your child. The sequence of all results believed to be medically relevant 
or important to your child’s or your own health will be validated at HudsonAlpha Clinical Services 
Laboratory in Huntsville, AL or another independent clinical laboratory. We expect the entire DNA 
analysis process to take 2-4 months. 
 
We do intend to perform analysis of each sample within our budgetary and technical means. If we 
are unable to analyze your samples you will be notified within 6 months of enrollment and sample 
collection. There is no cause for concern if you are told that we could not complete the analysis 
and provide you with results. 
 
Return of results is at the discretion of the clinicians and researchers involved with this study. If 
they identify results that may impact your child’s health, they may return those results to you. You 
will be scheduled for an appointment to discuss these findings with a genetic counselor or a 
trained healthcare provider. Only a subset of results believed to be important to your child’s 
medical care or those in line with the goals of this study will be reported to you. We will not 
provide you with all of the genetic information that we generate. At your results appointment, 
you may be provided with information regarding: 
● Primary findings - These findings will include information about a variant(s) (DNA change) 
that may potentially be the reason for your child’s phenotype (symptoms) or condition. 
o Most children will not receive a primary finding (or diagnosis). If no diagnosis is 
found, we will tell you. Even if we do not find a genetic diagnosis, your condition 
may still be the result of a change in your DNA that we are currently unable to 
identify. 
o If you receive a genetic diagnosis, this may not change your child’s prognosis or 
medical treatment. However it may help you and your doctor to better understand 
the cause of your child’s condition and the risks of similar conditions affecting your 
biological children. 
● Secondary findings – These findings may be reported to any study participant and may 
include any genetic changes that might impact your health or the health of your current or 
future children. These may include: 

Page 4 of 21 
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o Whether there are any changes in your DNA that could put you at a higher risk for 
developing a disease unrelated to your child’s condition in the future, such as cancer 
or heart disease. 
1. Some of these diseases may be medically useful and some may not be 
medically useful. We will not return results that are not medically useful. 
2. Some of these diseases will appear in childhood and others will appear 
when you are an adult. 
● Carrier status – In the event that we discover that your child’s symptoms are caused by a 
recessive genetic condition where he or she inherited one variant (DNA change) from each 
parent, we may provide information about whether or not you are a "carrier" for a genetic 
change that may be passed on to your biological children. 
We will arrange for a genetic counselor or a trained healthcare provider to discuss the results of 
the test with you. Educational materials will also be made available to you to help you better 
understand any results that you may or may no receive as part of this study. 
You will be actively enrolled in this study for up to one year however we may continue to access 
your medical record for up to 5 years. We plan to use coded information from our medical record 
to determine the impact of whole genome sequencing and genetic diagnosis on medical care. 
After you receive the results of the genetic test, you may be contacted by your physician or key 
study personnel to check on you or to ask follow-up questions. Your DNA samples may be stored 
indefinitely for future research unless you choose to withdraw from the study. Please note that 
participation in this study is voluntary and you may withdraw from this study at any time. 
 
You will also be presented with a baseline survey at the time of enrollment that you can complete 
online using Genome Gateway. The survey will ask you questions about basic demographics, how 
you feel about your child’s health and your experience in the hospital, how well you understand 
medical terms, math and genetics. After you receive results, you will be asked some of these same 
questions and some additional ones related to your health, your understanding of the genetics 
results returned, and how the results influence future planning at 1-month post-ROR, 4-months 
post-ROR, and 4.5-months post-ROR. 
 
Risks and Discomforts 
The risks of drawing blood include pain, bruising, lightheadedness, and fainting. Infection at the site 
of the needle stick is a rare side effect. These are the same risks you face any time you have a blood 
test. 
 
The main concerns associated with genetic testing are anxiety, depression, or other forms of 
emotional distress that may result from receiving genetic information about the suspected cause of 
your child’s condition. This is especially true for those diseases that are not treatable or preventable. 
Though some treatments have been shown to help individuals with certain genetic conditions, there 
is no "cure" for most. 

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When performing genetic testing, it may be discovered that family relationships are not as 
predicted. For example, a child might not be biologically related to his/her father, or two people who 
are married might turn out to be biologically related. These findings will not be disclosed as part of 
this study. 
In some cases, you may receive information about your carrier status and/or changes in your DNA 
that may impact your health. These findings will only be returned if they were inherited by your child 
who is enrolled in this study and suspected to contribute to their condition. Genetic changes in 
children that affect development may be inherited from one or both parents, even if the parents 
appear to be healthy. This information may affect the way you view or evaluate yourself or your 
family. It may also influence, or generate anxiety about, future family planning decisions. 
It is also important to keep in mind that you and your biological relatives have similar DNA 
sequences. This means that genetic information about your child may also have implications for your 
relatives if the variation was inherited. 
You may be referred to an additional physician or clinic for further testing or advice depending on 
the type of genetic information we generate from your sample. If you experience psychological 
distress or other difficulties, we can also refer you to an appropriate resource for care and/or 
support. 
 
There may be unforeseeable risks associated with receiving genetic information and the potential 
decisions, actions, or inactions that may be required in response to that information. Please consider 
this carefully and ask any questions that you may have before deciding whether or not to participate 
in this study. 
 
It is important that you consider the risks and uncertainties of this research study that make it 
different from traditional medical testing. 
 
We will make sure that the information that you are given is as accurate as possible to the best of 
our ability. We will use the best standards, practices, and technologies available to researchers. 
However, the technologies available to analyze DNA and our knowledge of how DNA affects health 
are changing rapidly. They are also subject to much uncertainty. Some DNA changes that are 
important to health may be missed, and other DNA changes that are not important may be 
incorrectly identified as if they are important. There are also moral and ethical questions about using 
genetic information on which scientific and medical communities have not yet reached a consensus. 
Therefore, we do NOT guarantee that our test will have the same levels of completeness, accuracy, 
or standardization associated with more traditional medical tests. 

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Before offering your consent to participate in this research study, please consider all of the risks 
associated with: 
● The return or possible lack of return of results; 
● Whether our interpretation of those results is accurate; 
● How you and/or your family will choose to act upon or not act upon the information or lack 
of information. 
Benefits 
You may not benefit directly from taking part in this study. However, your participation may lead to 
new discoveries that help to advance medical research and improve patient care, especially, but not 
only, newborn patient care in the future. Your participation in this study may help to make health 
care and access to health care broader and more representative. 
You may find out if there is a change in your child’s DNA that has altered their development. You 
might also find out if this change could affect future biological children. 
A genetic diagnosis may help you connect with other families in the community who face similar 
medical problems. While unlikely, it is possible that a genetic diagnosis may point your doctor to a 
better medical and/or educational treatment. 
 
You may discover that you or your child are at an increased risk for developing other diseases and 
that information may be of medical benefit. 
 
None of the above benefits are guaranteed, and it is expected that many participants will not receive 
specific information that is relevant to their health. 
 
Alternatives 
This is not a treatment study. Your alternative is not to participate in this research study. 
 
Confidentiality 
Information obtained about you for this study will be kept confidential to the extent allowed by law. 
However, research information that identifies you may be shared with people or organizations for 
quality assurance or data analysis, or with those responsible for ensuring compliance with laws and 
regulations related to research. They include: 
● the UAB Institutional Review Board (IRB). An IRB is a group that reviews the study to protect 
the rights and welfare of research participants. 
● Woman’s IRB, Woman’s Research and Development Committee, and Woman’s Health 
Research Department 
● the NIH National Human Genome Research Institute (NHGRI) 
● the Office for Human Research Protections (OHRP) 
 
The information from the research including your child’s clinical information, family history, and 
genetic variants may be published for scientific purposes; however, your identity will not be given out 
to anyone outside of the clinical team involved with the study. 

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Your consent form will be placed in your child’s medical record at Woman’s Hospital. This may 
include either a paper medical record or electronic medical record (EMR). An EMR is an electronic 
version of a paper medical record of your care within this health system. Your child’s EMR may 
indicate that you and your child are enrolled in this study and provide the name and contact 
information for the principal investigator. 
Results of research tests or procedures that have been clinically validated (i.e. Sanger reports) may be 
placed in your child’s medical record. All information within your medical record can be viewed by 
individuals authorized to access the record. 
Information relating to this study, including your name, medical record number, date of birth and 
social security number, may be shared with the billing offices of Woman’s Hospital so costs for clinical 
services can be appropriately paid for by either the study account or by your insurance. 
 
This research is covered by a Certificate of Confidentiality from the National Institutes of Health. The 
researchers with this Certificate may not disclose or use information, documents, or biospecimens 
that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other 
action, suit, or proceeding, or be used as evidence, for example, if there is a court subpoena, unless 
you have consented for this use. Information, documents, or biospecimens protected by this 
Certificate cannot be disclosed to anyone else who is not connected with the research except, if there 
is a federal, state, or local law that requires disclosure (such as to report child abuse or communicable 
diseases but not for federal, state, or local civil, criminal, administrative, legislative, or other 
proceedings, see below); if you have consented to the disclosure, including for your medical 
treatment; or if it is used for other scientific research, as allowed by federal regulations protecting 
research subjects. 
 
A federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes it illegal 
for health insurance companies, group health plans, and some employers to discriminate against you 
based on your genetic information. This law generally will protect you in the following ways: 
● Health insurance companies and group health plans may not request your genetic information 
that we get from this research. 
● Health insurance companies and group health plans may not use your genetic information 
when making decisions regarding your eligibility or premiums. 
● Employers with 15 or more employees may not use your genetic information that we get from 
this research when making a decision to hire, promote, or fire you or when setting the terms 
of your employment. 
 
Be aware this federal law does not protect you against genetic discrimination by companies that sell 
life insurance, disability insurance, or long-term care insurance, nor does it protect you against 
genetic discrimination by some employers. 

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A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this Web site at any time. 
Voluntary Participation and Withdrawal 
Whether or not you take part in this study is your choice. There will be no penalty if you decide not to 
be in the study. If you decide not to be in the study, you will not lose any benefits you are otherwise 
owed. You are free to withdraw from this research study at any time. Your choice to leave the study 
will not affect your relationship with any institution participating in this study. 
In the event that you chose to withdraw from the study: 
● No further genetic information from the study will be reported to you. 
● Your blood samples will be destroyed. 
● You will not be contacted to provide new information, additional samples, or 
participate in additional studies related to this project. 
● If the analysis of your DNA has been completed, this information will be retained for the 
study. 
If you would like to withdraw from the study, please contact Steven Spedale, MD, at 225-928-2555. 
 
Cost of Participation 
There will be no cost to you for taking part in this study. The blood draw, genomic sequencing and 
analysis, and genetic counseling related to this study will be provided to you at no cost during the 
study period. 
 
After you receive your research results, you may decide with your doctor or your child’s doctor to 
get more testing. The costs of your standard medical care or any services rendered in response to a 
genetic finding identified by this research project will be billed to you and/or your insurance 
company in the usual manner. This type of follow-up medical testing will be considered part of your 
clinical care, and will not be paid for by the research study. 
 
Payment for Participation in Research 
Participation in this study is voluntary and $25 will be provided for each survey completed for a total 
of $125 for your completion of all 5 study-related surveys. Ask the study staff about the method of 
payment that will be used for this study (e.g., check, cash, gift card, direct deposit); payment may 
take up to 4 weeks to process. 
 
Payment for Research-Related Injuries 
UAB, UMMC, HudsonAlpha, Woman’s Hospital, and NIH/NHGRI/sponsors of this research project 
have not provided for any payment if you are harmed as a result of taking part in this study. If such 
harm occurs, treatment will be provided. However, this treatment will not be provided free of charge. 

Page 9 of 21 
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Significant New Findings 
The study doctor or study staff will tell you if new information becomes available that might affect 
your choice to stay in the study. Please note that HudsonAlpha may, but is not required to, reanalyze 
your sample or report any new findings after results have been returned. 
Storage of Specimens for Future Use 
As part of this study, we would like to store some of the blood and DNA specimens collected from 
you and your child for validation of variants (to determine if a variant was inherited from a parent, 
etc.) identified by this project and for future research relevant to rare disease or other genetic 
disorders. The future research may be conducted by the study doctor or by other researchers that 
obtain IRB approval for their research. The specimens will be labeled with a code that only the study 
doctor can link back to you. Results of any future research will not be given to you or your doctor. The 
specimens obtained from you in this research may help in the development of a future commercial 
product. There are no plans to provide financial compensation to you should this occur. You do not 
have to agree to allow your specimens to be stored in order to be part of this study. 
You may at any time withdraw from the study and request that your specimens be removed from 
storage and not be used for future research. If you decide you want your specimens removed, you 
may contact Dr. Bruce Korf at 205-934-9411. Once the request is received, and if your samples have 
not already been used for other research, they will be destroyed. If you do not make such a request, 
your specimens will be stored indefinitely or until used. 
 
Initial next to your choice below: 
 
 
I agree to allow my specimens to be kept in the HudsonAlpha CSL and used for future genetics 
research. 
 
 
I do NOT agree to allow my specimens to be kept and used for future research. 
 
Genomic Data Sharing (GDS) 
We consider the privacy of your information to be of high priority and will take a variety of steps to 
ensure that privacy. However it is important for researchers to share some of the information that 
they learn from studying human samples. We will never share personally identifiable information, 
like names and addresses, with anyone outside of the research study. However, parts of your 
information may be shared. 
 
Some of your genetic information, limited to a very small subset that will not cause privacy loss risks 
to you, may be published in scientific journals or other unrestricted-access public venues to 
encourage sharing of the knowledge that may be learned by analyzing your DNA and DNA from other 
individuals. This could include information about your child’s symptoms, their age, and any genetic 
findings that we discover. 

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We may share coded lists of the DNA differences that we identify in public genetic databases. These 
databases gather genetic information from large groups of people and are pooled together such that 
no specific participant can be identified. 
There is a very small chance that some commercial value may result from the use of your donated 
samples or genetic information. If that happens, you will not receive a share in any profits. 
Unless you opt out, we may submit your complete genomic data along with some of your coded 
health information to an NIH-designated Data Repository such as dbGAP 
(http://www.ncbi.nlm.nih.gov/gap), AnVIL (https://anvilproject.org/), or another controlled access 
database. Access to dbGAP and AnVIL is only available to qualified researchers at qualified 
institutions who have agreed to abide by certain privacy safeguards, obligating them, both legally 
and ethically, to protect your privacy and to maintain information confidentiality. However, since 
your genetic information is unique to you, there is a small chance that someone could trace your 
information back to you. This risk is very small, but may grow in the future. Some risks and benefits 
are listed below: 
Risks: The risk of sharing your genomic data is that someone could link the information stored 
in the databases back to you. If your information suggests something about your health such 
as increased risk for disease, it could be misused. For example, it could be used to make it 
harder for you to get or keep a job or insurance or be used to discriminate against you or your 
family. There may also be other unknown risks. As stated above (confidentiality section of this 
form), there are federal protections against the misuse of your data (i.e. the Genetic 
Information Nondiscrimination Act, GINA). 
 
Benefits: There is no direct benefit to you from sharing your genomic data with NIH- 
designated repositories, however allowing researchers to use your data may lead to a better 
understanding of how genes affect health which may help other people in the future. 
 
Initial next to your choice below: 
 
 
 I agree for my genetic and other relevant study data, such as health information, to be shared 
with NIH-designated repositories such as dbGAP and AnVIL in a coded form for future research 
or analysis 
 
 I do NOT agree for my genetic and other relevant study data, such as health information, to be 
shared with NIH-designated repositories such as dbGAP and AnVIL in a coded form for future 
research or analysis 
 
Contact For Future Research 
As new research opportunities are identified, the researchers may wish to perform additional tests 
on fresh samples or invite eligible participants to enroll in new studies. We would like permission to 
contact you in the future, however this is not a requirement to participate in this study. A separate 
consent form will be obtained if you wish to participate in future research. 

Page 11 of 21 
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Initial next to your choice below: 
 
 
You have permission to contact me about new research opportunities that may interest me. 
 
 
You do NOT have permission to contact me about new research opportunities. 
 
Secondary Findings 
One unanimous decision to receive or not to receive secondary findings must be made by each 
participant family. Because parental samples are only used for confirmation of variation identified in 
the child’s whole genome sequence for this project, only those secondary findings identified in the 
child will be confirmed in the parental samples. Participant families may opt to receive this 
information, if available. If a family chooses to do so, information about an identified secondary 
finding will be included in the child’s medical record. Nothing will be placed in the parent’s medical 
record. 
 
 
Initial next to your choice below: 
 
 
 
 We (child and parent(s), if enrolled) would like to receive information about secondary 
findings. 
 
 
 We (child and parent(s), if enrolled) would NOT like to receive information about secondary 
findings. 
 
Questions 
If you have any questions, concerns, or complaints about the research or a research-related injury 
including available treatments, please contact Dr. Bruce Korf at 205-934-9411 or Dr. Steven Spedale 
at 225-928-2555. 
 
If you have questions about your rights as a research participant, or concerns or complaints about the 
research, you may contact, Ericka Seidemann, Human Protections Administrator at Woman’s 
Hospital, at 225-231-5296 or ericka.seidemann@womans.org. 
 
Legal Rights 
You are not waiving any of your legal rights by signing this consent form. 

Page 12 of 21 
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Signatures 
Your signature below indicates that you have read (or been read) the information 
provided above and agree to have your child participate in this study. You will receive a copy of this 
signed consent form. 
Your signature below indicates that you have read (or been read) the information provided above 
and agree to participate in this study. You will receive a copy of this signed consent form. 
 
 
Name of Proband Child (printed) 
 
 
Signature of Parent or Legally Authorized Representative 
Date 
 
 
 
Mother/Father/Caregiver 
Name of Parent Participant (printed) 
Relationship 
 
 
Signature of Parent Participant 
Date 
 
Mother/Father/Caregiver 
Name of Parent Participant (printed) 
Relationship 
 
 
Signature of Parent Participant 
Date 
 
 
 
 
Signature of Person Obtaining Consent 
Date 
 
In this research study, one consent form may be used to waive consent for the infant and capture 
informed consent of both parents; however, a separate HIPPA Authorization form will be completed 
for each participant. 
 
 
Waiver of Assent 
 
The assent of   
 
 
(name of child/minor) was waived because of: 
Age  
 
Maturity  
 
 Psychological state of the child  
 

P a g e 1 3 of 2 1 
V ersi o n D at e:  0 2/ 1 4/ 2 0 2 0 
 
P ur p o s e of R el e a s e 
I N F A N T 
W O M A N’ S H O S PI T A L 
M e di c al R e c or d N u m b er:    
 
 
A ut h oriz ati o n t o R el e as e H e alt h I nf or m ati o n fr o m W o m a n’s H os pit al 
P ati e nt’ s N a m e 
 
 
P ati e nt’ s D at e of Birt h 
 
 
I h er e b y a ut h ori z e a p pr o pri at e p er s o n n el at W O M A N S H O S PI T A L t o r el e a s e m y h e alt h 
i nf or m ati o n t o, a n d/ or all o w m y r e c or d s t o b e r e vi e w e d b y: 
 
R e ci pi e nt( s) 
St u d y d o ct or s, n ur s e s, a n d p er s o n n el; p u bli c h e alt h a g e n ci e s a n d g o v er n m e nt 
a g e n ci e s a s r e q uir e d b y l a w; W o m a n’ s I n stit uti o n al R e vi e w B o ar d; U A B I n stit uti o n al 
R e vi e w B o ar d; W o m a n’ s R e s e ar c h a n d D e v el o p m e nt C o m mitt e e; W o m a n’ s H e alt h 
R e s e ar c h D e p art m e nt; NI H N ati o n al H u m a n G e n o m e R e s e ar c h I n stit ut e ( N H G RI) 
R e ci pi e nt’ s 
A d dr e s s 
 
Att e nti o n: 
 
 
 f or Tr e at m e nt at A n ot h er F a cilit y 
 f or A p pli c ati o n f or I n s ur a n c e 
 f or Tr e at m e nt b y a P h y si ci a n 
x f or R e s e ar c h 
 f or Pr o c e s si n g of m y I n s ur a n c e Cl ai m 
 P er s o n al ( at m y r e q u e st) 
 f or a n I nt er vi e w 
 f or P u bli c ati o n, Br o a d c a st, or Ot h er Di s s e mi n ati o n b y t h e h o s pit al or m e di a 
 Ot h er R e a s o n s; S p e cif y:   
 
 
S p e cif y i nf or m ati o n t o b e r el e a s e d b y pl a ci n g a c h e c k m ar k i n t h e a p pr o pri at e b o x( e s): 
D at es of 
S er vic es 
 
 
x E ntir e R e c or d 
 Tr e at m e nt R o o m R e c or d 
 Di a g n o si s 
 Cli ni c R e c or d 
 Hi st or y & P h y si c al E x a mi n ati o n R e p ort s 
 E ntir e Billi n g R e c or d 
 P h y si ci a n’ s Pr o gr e s s N ot e s 
 It e mi z e d Bill 
 P h y si ci a n’ s Or d er s 
 D e m o gr a p hi c I nf or m ati o n 
 N ur s e’ s N ot e s 
 X- R a y R e p ort s 
 Di s c h ar g e S u m m ar y 
 L a b R e s ult s 
 O p er ati v e R e p ort 
 P h ot o gr a p h/ Vi d e o 
 C o n s ult ati o n R e p ort s; S p e cif y b y D o ct or    
 
 Ot h er R e c or d s; S p e cif y  
 
 I nf or m ati o n C o n c er ni n g Ill n e s s, s ur g er y, or e v e nt s s urr o u n di n g t h e birt h of m y c hil d 
 
S p e ci al c o n s e nt i s r e q uir e d t o r el e a s e t h e f oll o wi n g i nf or m ati o n.  I n di c at e 

P a g e 1 4 of 2 1
V ersi o n D at e: 0 2/ 1 4/ 2 0 2 0
M A R K E TI N G
A ut h ori z ati o n E x pir ati o n  D at e or E v e nt
x Al c o h ol a b u s e r e c or d s/t e st r e s ult s/ di a g n o si s
x HI V or AI D S t e st r e s ult s
x Dr u g A b u s e r e c or d s/t e st s r e s ult s/ di a g n o si s
x M e nt al  Di s or d er r e c or d s/t e st 
r e s ult s/ di a g n o si s G E N E TI C T E S T R E S U L T S – Y o u m u st s p e cif y t h e t e st r e s ult s t o b e 
r el e a s e d b y c h e c ki n g or writi n g b el o w:
C hr o m o s o m e A n al y si s ( s p e cif y b el o w):
F a ct or V L ei d e n
M et h yl e n et etr a h y dr of ol at e  R e d u ct a s e
Bl o o d
B o n e  M arr o w
C V S
Pr ot hr o m bi n  D N A
H er 2/ n e u Fi s h f or br e a st c a n c er
A m ni oti c Fl ui d
Ti s s u e
C y sti c Fi br o si s
x Ot h er _ A N Y  G E N E TI C T E S TI N G  R E S U L T S
If I a m pr o vi di n g a ut h ori z ati o n f or  m ar k eti n g p ur p o s e s, I u n d er st a n d t h at
W o m a n’ s  H o s pit al  will n ot r e c ei v e a m o n et ar y b e n efit fr o m a t hir d p art y f or t h e u s e of m y 
p ati e nt i nf or m ati o n.
W o m a n’ s  H o s pit al  will r e c ei v e a m o n et ar y b e n efit ( dir e ctl y or i n dir e ctl y) fr o m a t hir d p art y 
f or t h e u s e of m y p ati e nt i nf or m ati o n.
U nl e s s ot h er wi s e r e v o k e d, t hi s a ut h ori z ati o n will e x pir e o n t h e i n di c at e d d at e, e v e nt or 
c o n diti o n. If a n e x pir ati o n d at e, e v e nt or c o n diti o n i s n ot s p e cifi e d b el o w, t hi s a ut h ori z ati o n 
will e x pir e si x ( 6)  m o nt h s fr o m d at e of si g n at ur e. F or g e n eti c i nf or m ati o n, t h e e x pir ati o n d at e 
m u st b e si xt y d a y s or l e s s fr o m d at e of si g n at ur e. If n o e x pir ati o n d at e i s s p e cifi e d, t h e 
a ut h ori z ati o n will e x pir e si xt y d a y s fr o m d at e of si g n at ur e. T h e st at e m e nt “ e n d of r e s e ar c h,” 
“ n o n e,” or si mil ar l a n g u a g e i s s uffi ci e nt if di s cl o s ur e i s f or r e s e ar c h, ( e x c e pt f or r e s e ar c h o n 
g e n eti c i nf or m ati o n) i n cl u di n g t h e cr e ati o n a n d m ai nt e n a n c e of a r e s e ar c h d at a b a s e or 
r e p o sit or y.
E x pir ati o n ( M o nt h, D a y, Y e ar / E v e nt / C o n diti o n)     
6 0 d a y s fr o m 
si g n at ur e
R E Q UI R E D S T A T E M E N T S
I u n d er st a n d t h at: 
1.
A ut h ori zi n g t h e r el e a s e of t hi s h e alt h i nf or m ati o n i s v ol u nt ar y a n d I c a n r ef u s e t o si g n t hi s 
a ut h ori z ati o n.
2. I h a v e t h e ri g ht t o r e v o k e t hi s a ut h ori z ati o n at a n y ti m e ( u p o n writt e n n otifi c ati o n t o t h e 
H e alt h I nf or m ati o n M a n a g e m e nt D e p art m e nt at W o m a n’ s H o s pit al) e x c e pt t o t h e e xt e nt 
t h at W o m a n’ s H o s pit al h a s alr e a d y r el e a s e d t h e h e alt h i nf or m ati o n b ef or e r e c ei pt of t h e 
r e v o c ati o n. F or g e n eti c i nf or m ati o n, I h a v e t h e ri g ht t o r e v o k e t h e a ut h ori z ati o n at a n y ti m e 
b ef or e t h e di s cl o s ur e i s a ct u all y m a d e or w h e n I a m m a d e a w ar e of t h e d et ail s of t h e 
g e n eti c i nf or m ati o n.
Y o ur  A ut h ori z ati o n b y pl a ci n g a c h e c k m ar k i n t h e a p pr o pri at e b o x( e s).  N O
I N F O R M A TI O N WI L L B E R E L E A S E D I F B O X I S N O T C H E C K E D

P a g e 1 5 of 2 1 
V ersi o n D at e:  0 2/ 1 4/ 2 0 2 0 
 
 
 
 
P E R S O N AL R E P R E S E N T A TI V E 
3.  If t h e a ut h ori z ati o n i s f or r e s e ar c h, t h e r e s e ar c h er m a y c o nti n u e t o u s e a n d di s cl o s e t h e 
h e alt h i nf or m ati o n c oll e ct e d pri or t o t h e r e c ei pt of t h e writt e n r e v o c ati o n. 
4.  W o m a n’ s H o s pit al c a n n ot c o n diti o n tr e at m e nt, p a y m e nt, e nr oll m e nt, or eli gi bilit y f or 
b e n efit s o n t h e p ati e nt pr o vi di n g t hi s a ut h ori z ati o n. 
5.  If t h e a ut h ori z ati o n i s f or r e s e ar c h-r el at e d tr e at m e nt, W o m a n’ s H o s pit al m a y c o n diti o n t h e 
pr o vi si o n of r e s e ar c h-r el at e d tr e at m e nt o n pr o vi si o n of a n a ut h ori z ati o n f or t h e u s e or 
di s cl o s ur e of pr ot e ct e d h e alt h i nf or m ati o n f or s u c h r e s e ar c h. 
6.  A n y r el e a s e of i nf or m ati o n c arri e s wit h it t h e p ot e nti al f or a n u n a ut h ori z e d r e di s cl o s ur e b y 
t h e R e ci pi e nt a n d t h e i nf or m ati o n m a y n ot b e pr ot e ct e d b y f e d er al l a w. 
7.  T h e a ut h ori z ati o n s h all b e i n v ali d if u s e d f or a n y ot h er p ur p o s e ot h er t h a n t h e d e s cri b e d 
p ur p o s e f or w hi c h t h e di s cl o s ur e i s m a d e. 
8.  A p h ot o c o p y of t hi s a ut h ori z ati o n m a y s er v e a s a n ori gi n al. 
 
 
P ati e nt’ s Si g n at ur e 
D at e 
 
 
P er s o n al R e pr e s e nt ati v e’ s Si g n at ur e (if n e c e s s ar y)  
D at e 
 
If it i s n e c e s s ar y f or a p er s o n al r e pr e s e nt ati v e t o si g n a n d d at e t hi s a ut h ori z ati o n d u e t o l a c k 
of c a p a cit y of t h e p ati e nt, i n cl u di n g mi n orit y, i nt er di cti o n or a n y ot h er l e g al r e a s o n, i n di c at e 
b el o w h o w t h e p er s o n si g ni n g a s r e pr e s e nt ati v e h a s a ut h orit y t o d o s o: 
  T h e c o urt a p p oi nt e d p er s o n a cti n g f or t h e p ati e nt, if o n e h a s b e e n a p p oi nt e d. 
 A n a g e nt a cti n g p ur s u a nt t o a v ali d m a n d at e, s p e cifi c all y a ut h ori zi n g t h e a g e nt t o m a k e 
h e alt h c ar e d e ci si o n s. 
 T h e p ati e nt’ s s p o u s e n ot j u di ci all y s e p ar at e d. 
 A n a d ult c hil d of t h e p ati e nt. 
  A n y p ar e nt, w h et h er a d ult or mi n or, f or hi s mi n or c hil d. 
 T h e p ati e nt’ s si bli n g. 
 T h e p ati e nt’ s ot h er a s c e n d a nt s or d e s c e n d a nt s. 
 A n y p er s o n t e m p or aril y st a n di n g i n f or t h e p ar e nt s, w h et h er f or m all y s er vi n g or n ot, f or a 
mi n or u n d er hi s c ar e a n d a n y g u ar di a n f or hi s w ar d. 
 Ot h er ( Pl e a s e s p e cif y):   
 
F or Offi c e U s e O nl y: 
D at e c o p y of a ut h ori z ati o n gi v e n t o p ati e nt   
 
D at e c o p y of a ut h ori z ati o n m ail e d t o p ati e nt   
   
D at e r e c or d s s e nt 
R e vi s e d: 1 1/ 0 4 

P a g e 1 6 of 2 1 
V ersi o n D at e:  0 2/ 1 4/ 2 0 2 0 
 
P ur p o s e of R el e a s e 
M O T H E R  
W O M A N’ S H O S PI T A L 
M e di c al R e c or d N u m b er:    
 
 
A ut h oriz ati o n t o R el e as e H e alt h I nf or m ati o n fr o m W o m a n’s H os pit al 
P ati e nt’ s N a m e 
 
 
P ati e nt’ s D at e of Birt h 
 
 
I h er e b y a ut h ori z e a p pr o pri at e p er s o n n el at W O M A N S H O S PI T A L t o r el e a s e m y h e alt h 
i nf or m ati o n t o, a n d/ or all o w m y r e c or d s t o b e r e vi e w e d b y: 
 
R e ci pi e nt( s) 
St u d y d o ct or s, n ur s e s, a n d p er s o n n el; p u bli c h e alt h a g e n ci e s a n d g o v er n m e nt 
a g e n ci e s a s r e q uir e d b y l a w; W o m a n’ s I n stit uti o n al R e vi e w B o ar d; U A B I n stit uti o n al 
R e vi e w B o ar d; W o m a n’ s R e s e ar c h a n d D e v el o p m e nt C o m mitt e e; W o m a n’ s H e alt h 
R e s e ar c h D e p art m e nt; NI H N ati o n al H u m a n G e n o m e R e s e ar c h I n stit ut e ( N H G RI) 
R e ci pi e nt’ s 
A d dr e s s 
 
Att e nti o n: 
 
 
 f or Tr e at m e nt at A n ot h er F a cilit y 
 f or A p pli c ati o n f or I n s ur a n c e 
 f or Tr e at m e nt b y a P h y si ci a n 
x f or R e s e ar c h 
 f or Pr o c e s si n g of m y I n s ur a n c e Cl ai m 
 P er s o n al ( at m y r e q u e st) 
 f or a n I nt er vi e w 
 f or P u bli c ati o n, Br o a d c a st, or Ot h er Di s s e mi n ati o n b y t h e h o s pit al or m e di a 
 Ot h er R e a s o n s; S p e cif y:   
 
 
S p e cif y i nf or m ati o n t o b e r el e a s e d b y pl a ci n g a c h e c k m ar k i n t h e a p pr o pri at e b o x( e s): 
D at es of 
S er vic es 
 
 
 E ntir e R e c or d 
 Tr e at m e nt R o o m R e c or d 
 Di a g n o si s 
 Cli ni c R e c or d 
 Hi st or y & P h y si c al E x a mi n ati o n R e p ort s 
 E ntir e Billi n g R e c or d 
 P h y si ci a n’ s Pr o gr e s s N ot e s 
 It e mi z e d Bill 
 P h y si ci a n’ s Or d er s 
 D e m o gr a p hi c I nf or m ati o n 
 N ur s e’ s N ot e s 
 X- R a y R e p ort s 
 Di s c h ar g e S u m m ar y 
 L a b R e s ult s 
 O p er ati v e R e p ort 
 P h ot o gr a p h/ Vi d e o 
 C o n s ult ati o n R e p ort s; S p e cif y b y D o ct or    
 
 Ot h er R e c or d s; S p e cif y  
 
 I nf or m ati o n C o n c er ni n g Ill n e s s, s ur g er y, or e v e nt s s urr o u n di n g t h e birt h of m y c hil d 
 
S p e ci al c o n s e nt i s r e q uir e d t o r el e a s e t h e f oll o wi n g i nf or m ati o n.  I n di c at e 

P a g e 1 7 of 2 1
V ersi o n D at e: 0 2/ 1 4/ 2 0 2 0
M A R K E TI N G
A ut h ori z ati o n E x pir ati o n  D at e or E v e nt
x Al c o h ol a b u s e r e c or d s/t e st r e s ult s/ di a g n o si s
x HI V or AI D S t e st r e s ult s
x Dr u g A b u s e r e c or d s/t e st s r e s ult s/ di a g n o si s
x M e nt al  Di s or d er r e c or d s/t e st 
r e s ult s/ di a g n o si s G E N E TI C T E S T R E S U L T S – Y o u m u st s p e cif y t h e t e st r e s ult s t o b e 
r el e a s e d b y c h e c ki n g or writi n g b el o w:
C hr o m o s o m e A n al y si s ( s p e cif y b el o w):
F a ct or V L ei d e n
M et h yl e n et etr a h y dr of ol at e  R e d u ct a s e
Bl o o d
B o n e  M arr o w
C V S
Pr ot hr o m bi n  D N A
H er 2/ n e u Fi s h f or br e a st c a n c er
A m ni oti c Fl ui d
Ti s s u e
C y sti c Fi br o si s
x Ot h er _ A N Y  G E N E TI C T E S TI N G  R E S U L T S
If I a m pr o vi di n g a ut h ori z ati o n f or  m ar k eti n g p ur p o s e s, I u n d er st a n d t h at
W o m a n’ s  H o s pit al  will n ot r e c ei v e a m o n et ar y b e n efit fr o m a t hir d p art y f or t h e u s e of m y 
p ati e nt i nf or m ati o n.
W o m a n’ s  H o s pit al  will r e c ei v e a m o n et ar y b e n efit ( dir e ctl y or i n dir e ctl y) fr o m a t hir d p art y 
f or t h e u s e of m y p ati e nt i nf or m ati o n.
U nl e s s ot h er wi s e r e v o k e d, t hi s a ut h ori z ati o n will e x pir e o n t h e i n di c at e d d at e, e v e nt or 
c o n diti o n. If a n e x pir ati o n d at e, e v e nt or c o n diti o n i s n ot s p e cifi e d b el o w, t hi s a ut h ori z ati o n 
will e x pir e si x ( 6)  m o nt h s fr o m d at e of si g n at ur e. F or g e n eti c i nf or m ati o n, t h e e x pir ati o n d at e 
m u st b e si xt y d a y s or l e s s fr o m d at e of si g n at ur e. If n o e x pir ati o n d at e i s s p e cifi e d, t h e 
a ut h ori z ati o n will e x pir e si xt y d a y s fr o m d at e of si g n at ur e. T h e st at e m e nt “ e n d of r e s e ar c h,” 
“ n o n e,” or si mil ar l a n g u a g e i s s uffi ci e nt if di s cl o s ur e i s f or r e s e ar c h, ( e x c e pt f or r e s e ar c h o n 
g e n eti c i nf or m ati o n) i n cl u di n g t h e cr e ati o n a n d m ai nt e n a n c e of a r e s e ar c h d at a b a s e or 
r e p o sit or y.
E x pir ati o n ( M o nt h, D a y, Y e ar / E v e nt / C o n diti o n)     
6 0 d a y s fr o m 
si g n at ur e
R E Q UI R E D S T A T E M E N T S
I u n d er st a n d t h at: 
9.
A ut h ori zi n g t h e r el e a s e of t hi s h e alt h i nf or m ati o n i s v ol u nt ar y a n d I c a n r ef u s e t o si g n t hi s 
a ut h ori z ati o n.
1 0. I h a v e t h e ri g ht t o r e v o k e t hi s a ut h ori z ati o n at a n y ti m e ( u p o n writt e n n otifi c ati o n t o t h e 
H e alt h I nf or m ati o n M a n a g e m e nt D e p art m e nt at W o m a n’ s H o s pit al) e x c e pt t o t h e e xt e nt 
t h at W o m a n’ s H o s pit al h a s alr e a d y r el e a s e d t h e h e alt h i nf or m ati o n b ef or e r e c ei pt of t h e 
r e v o c ati o n. F or g e n eti c i nf or m ati o n, I h a v e t h e ri g ht t o r e v o k e t h e a ut h ori z ati o n at a n y ti m e 
b ef or e t h e di s cl o s ur e i s a ct u all y m a d e or w h e n I a m m a d e a w ar e of t h e d et ail s of t h e 
g e n eti c i nf or m ati o n.
Y o ur  A ut h ori z ati o n b y pl a ci n g a c h e c k m ar k i n t h e a p pr o pri at e b o x( e s).  N O
I N F O R M A TI O N WI L L B E R E L E A S E D I F B O X I S N O T C H E C K E D

P a g e 1 8 of 2 1 
V ersi o n D at e:  0 2/ 1 4/ 2 0 2 0 
 
 
 
 
P E R S O N AL R E P R E S E N T A TI V E 
1 1. If t h e a ut h ori z ati o n i s f or r e s e ar c h, t h e r e s e ar c h er m a y c o nti n u e t o u s e a n d di s cl o s e t h e 
h e alt h i nf or m ati o n c oll e ct e d pri or t o t h e r e c ei pt of t h e writt e n r e v o c ati o n. 
1 2. W o m a n’ s H o s pit al c a n n ot c o n diti o n tr e at m e nt, p a y m e nt, e nr oll m e nt, or eli gi bilit y f or 
b e n efit s o n t h e p ati e nt pr o vi di n g t hi s a ut h ori z ati o n. 
1 3. If t h e a ut h ori z ati o n i s f or r e s e ar c h-r el at e d tr e at m e nt, W o m a n’ s H o s pit al m a y c o n diti o n t h e 
pr o vi si o n of r e s e ar c h-r el at e d tr e at m e nt o n pr o vi si o n of a n a ut h ori z ati o n f or t h e u s e or 
di s cl o s ur e of pr ot e ct e d h e alt h i nf or m ati o n f or s u c h r e s e ar c h. 
1 4. A n y r el e a s e of i nf or m ati o n c arri e s wit h it t h e p ot e nti al f or a n u n a ut h ori z e d r e di s cl o s ur e b y 
t h e R e ci pi e nt a n d t h e i nf or m ati o n m a y n ot b e pr ot e ct e d b y f e d er al l a w. 
1 5. T h e a ut h ori z ati o n s h all b e i n v ali d if u s e d f or a n y ot h er p ur p o s e ot h er t h a n t h e d e s cri b e d 
p ur p o s e f or w hi c h t h e di s cl o s ur e i s m a d e. 
1 6. A p h ot o c o p y of t hi s a ut h ori z ati o n m a y s er v e a s a n ori gi n al. 
 
 
P ati e nt’ s Si g n at ur e 
D at e 
 
 
P er s o n al R e pr e s e nt ati v e’ s Si g n at ur e (if n e c e s s ar y)  
D at e 
 
If it i s n e c e s s ar y f or a p er s o n al r e pr e s e nt ati v e t o si g n a n d d at e t hi s a ut h ori z ati o n d u e t o l a c k 
of c a p a cit y of t h e p ati e nt, i n cl u di n g mi n orit y, i nt er di cti o n or a n y ot h er l e g al r e a s o n, i n di c at e 
b el o w h o w t h e p er s o n si g ni n g a s r e pr e s e nt ati v e h a s a ut h orit y t o d o s o: 
  T h e c o urt a p p oi nt e d p er s o n a cti n g f or t h e p ati e nt, if o n e h a s b e e n a p p oi nt e d. 
 A n a g e nt a cti n g p ur s u a nt t o a v ali d m a n d at e, s p e cifi c all y a ut h ori zi n g t h e a g e nt t o m a k e 
h e alt h c ar e d e ci si o n s. 
 T h e p ati e nt’ s s p o u s e n ot j u di ci all y s e p ar at e d. 
 A n a d ult c hil d of t h e p ati e nt. 
  A n y p ar e nt, w h et h er a d ult or mi n or, f or hi s mi n or c hil d. 
 T h e p ati e nt’ s si bli n g. 
 T h e p ati e nt’ s ot h er a s c e n d a nt s or d e s c e n d a nt s. 
 A n y p er s o n t e m p or aril y st a n di n g i n f or t h e p ar e nt s, w h et h er f or m all y s er vi n g or n ot, f or a 
mi n or u n d er hi s c ar e a n d a n y g u ar di a n f or hi s w ar d. 
 Ot h er ( Pl e a s e s p e cif y):   
 
F or Offi c e U s e O nl y: 
D at e c o p y of a ut h ori z ati o n gi v e n t o p ati e nt   
 
D at e c o p y of a ut h ori z ati o n m ail e d t o p ati e nt   
   
D at e r e c or d s s e nt 
R e vi s e d: 1 1/ 0 4 

P a g e 1 9 of 2 1 
V ersi o n D at e:  0 2/ 1 4/ 2 0 2 0 
 
P ur p o s e of R el e a s e 
F A T H E R  
W O M A N’ S H O S PI T A L 
M e di c al R e c or d N u m b er:    
 
 
A ut h oriz ati o n t o R el e as e H e alt h I nf or m ati o n fr o m W o m a n’s H os pit al 
P ati e nt’ s N a m e 
 
 
P ati e nt’ s D at e of Birt h 
 
 
I h er e b y a ut h ori z e a p pr o pri at e p er s o n n el at W O M A N S H O S PI T A L t o r el e a s e m y h e alt h 
i nf or m ati o n t o, a n d/ or all o w m y r e c or d s t o b e r e vi e w e d b y: 
 
R e ci pi e nt( s) 
St u d y d o ct or s, n ur s e s, a n d p er s o n n el; p u bli c h e alt h a g e n ci e s a n d g o v er n m e nt 
a g e n ci e s a s r e q uir e d b y l a w; W o m a n’ s I n stit uti o n al R e vi e w B o ar d; U A B I n stit uti o n al 
R e vi e w B o ar d; W o m a n’ s R e s e ar c h a n d D e v el o p m e nt C o m mitt e e; W o m a n’ s H e alt h 
R e s e ar c h D e p art m e nt; NI H N ati o n al H u m a n G e n o m e R e s e ar c h I n stit ut e ( N H G RI) 
R e ci pi e nt’ s 
A d dr e s s 
 
Att e nti o n: 
 
 
 f or Tr e at m e nt at A n ot h er F a cilit y 
 f or A p pli c ati o n f or I n s ur a n c e 
 f or Tr e at m e nt b y a P h y si ci a n 
x f or R e s e ar c h 
 f or Pr o c e s si n g of m y I n s ur a n c e Cl ai m 
 P er s o n al ( at m y r e q u e st) 
 f or a n I nt er vi e w 
 f or P u bli c ati o n, Br o a d c a st, or Ot h er Di s s e mi n ati o n b y t h e h o s pit al or m e di a 
 Ot h er R e a s o n s; S p e cif y:   
 
 
S p e cif y i nf or m ati o n t o b e r el e a s e d b y pl a ci n g a c h e c k m ar k i n t h e a p pr o pri at e b o x( e s): 
D at es of 
S er vic es 
 
 
 E ntir e R e c or d 
 Tr e at m e nt R o o m R e c or d 
 Di a g n o si s 
 Cli ni c R e c or d 
 Hi st or y & P h y si c al E x a mi n ati o n R e p ort s 
 E ntir e Billi n g R e c or d 
 P h y si ci a n’ s Pr o gr e s s N ot e s 
 It e mi z e d Bill 
 P h y si ci a n’ s Or d er s 
 D e m o gr a p hi c I nf or m ati o n 
 N ur s e’ s N ot e s 
 X- R a y R e p ort s 
 Di s c h ar g e S u m m ar y 
 L a b R e s ult s 
 O p er ati v e R e p ort 
 P h ot o gr a p h/ Vi d e o 
 C o n s ult ati o n R e p ort s; S p e cif y b y D o ct or    
 
 Ot h er R e c or d s; S p e cif y  
 
 I nf or m ati o n C o n c er ni n g Ill n e s s, s ur g er y, or e v e nt s s urr o u n di n g t h e birt h of m y c hil d 
 
S p e ci al c o n s e nt i s r e q uir e d t o r el e a s e t h e f oll o wi n g i nf or m ati o n.  I n di c at e 

P a g e 2 0 of 2 1
V ersi o n D at e: 0 2/ 1 4/ 2 0 2 0
M A R K E TI N G
A ut h ori z ati o n E x pir ati o n  D at e or E v e nt
x Al c o h ol a b u s e r e c or d s/t e st r e s ult s/ di a g n o si s
x HI V or AI D S t e st r e s ult s
x Dr u g A b u s e r e c or d s/t e st s r e s ult s/ di a g n o si s
x M e nt al  Di s or d er r e c or d s/t e st 
r e s ult s/ di a g n o si s G E N E TI C T E S T R E S U L T S – Y o u m u st s p e cif y t h e t e st r e s ult s t o b e 
r el e a s e d b y c h e c ki n g or writi n g b el o w:
C hr o m o s o m e A n al y si s ( s p e cif y b el o w):
F a ct or V L ei d e n
M et h yl e n et etr a h y dr of ol at e  R e d u ct a s e
Bl o o d
B o n e  M arr o w
C V S
Pr ot hr o m bi n  D N A
H er 2/ n e u Fi s h f or br e a st c a n c er
A m ni oti c Fl ui d
Ti s s u e
C y sti c Fi br o si s
x Ot h er _ A N Y  G E N E TI C T E S TI N G  R E S U L T S
If I a m pr o vi di n g a ut h ori z ati o n f or  m ar k eti n g p ur p o s e s, I u n d er st a n d t h at
W o m a n’ s  H o s pit al  will n ot r e c ei v e a m o n et ar y b e n efit fr o m a t hir d p art y f or t h e u s e of m y 
p ati e nt i nf or m ati o n.
W o m a n’ s  H o s pit al  will r e c ei v e a m o n et ar y b e n efit ( dir e ctl y or i n dir e ctl y) fr o m a t hir d p art y 
f or t h e u s e of m y p ati e nt i nf or m ati o n.
U nl e s s ot h er wi s e r e v o k e d, t hi s a ut h ori z ati o n will e x pir e o n t h e i n di c at e d d at e, e v e nt or 
c o n diti o n. If a n e x pir ati o n d at e, e v e nt or c o n diti o n i s n ot s p e cifi e d b el o w, t hi s a ut h ori z ati o n 
will e x pir e si x ( 6)  m o nt h s fr o m d at e of si g n at ur e. F or g e n eti c i nf or m ati o n, t h e e x pir ati o n d at e 
m u st b e si xt y d a y s or l e s s fr o m d at e of si g n at ur e. If n o e x pir ati o n d at e i s s p e cifi e d, t h e 
a ut h ori z ati o n will e x pir e si xt y d a y s fr o m d at e of si g n at ur e. T h e st at e m e nt “ e n d of r e s e ar c h,” 
“ n o n e,” or si mil ar l a n g u a g e i s s uffi ci e nt if di s cl o s ur e i s f or r e s e ar c h, ( e x c e pt f or r e s e ar c h o n 
g e n eti c i nf or m ati o n) i n cl u di n g t h e cr e ati o n a n d m ai nt e n a n c e of a r e s e ar c h d at a b a s e or 
r e p o sit or y.
E x pir ati o n ( M o nt h, D a y, Y e ar / E v e nt / C o n diti o n)     
6 0 d a y s fr o m 
si g n at ur e
R E Q UI R E D S T A T E M E N T S
I u n d er st a n d t h at: 
1 7. A ut h ori zi n g t h e r el e a s e of t hi s h e alt h i nf or m ati o n i s v ol u nt ar y a n d I c a n r ef u s e t o si g n t hi s 
a ut h ori z ati o n.
1 8. I h a v e t h e ri g ht t o r e v o k e t hi s a ut h ori z ati o n at a n y ti m e ( u p o n writt e n n otifi c ati o n t o t h e 
H e alt h I nf or m ati o n M a n a g e m e nt D e p art m e nt at W o m a n’ s H o s pit al) e x c e pt t o t h e e xt e nt 
t h at W o m a n’ s H o s pit al h a s alr e a d y r el e a s e d t h e h e alt h i nf or m ati o n b ef or e r e c ei pt of t h e 
r e v o c ati o n. F or g e n eti c i nf or m ati o n, I h a v e t h e ri g ht t o r e v o k e t h e a ut h ori z ati o n at a n y ti m e 
b ef or e t h e di s cl o s ur e i s a ct u all y m a d e or w h e n I a m m a d e a w ar e of t h e d et ail s of t h e 
g e n eti c i nf or m ati o n.
Y o ur  A ut h ori z ati o n b y pl a ci n g a c h e c k m ar k i n t h e a p pr o pri at e b o x( e s).  N O
I N F O R M A TI O N WI L L B E R E L E A S E D I F B O X I S N O T C H E C K E D

P a g e 2 1 of 2 1 
V ersi o n D at e:  0 2/ 1 4/ 2 0 2 0 
 
 
 
 
P E R S O N AL R E P R E S E N T A TI V E 
1 9. If t h e a ut h ori z ati o n i s f or r e s e ar c h, t h e r e s e ar c h er m a y c o nti n u e t o u s e a n d di s cl o s e t h e 
h e alt h i nf or m ati o n c oll e ct e d pri or t o t h e r e c ei pt of t h e writt e n r e v o c ati o n. 
2 0. W o m a n’ s H o s pit al c a n n ot c o n diti o n tr e at m e nt, p a y m e nt, e nr oll m e nt, or eli gi bilit y f or 
b e n efit s o n t h e p ati e nt pr o vi di n g t hi s a ut h ori z ati o n. 
2 1. If t h e a ut h ori z ati o n i s f or r e s e ar c h-r el at e d tr e at m e nt, W o m a n’ s H o s pit al m a y c o n diti o n t h e 
pr o vi si o n of r e s e ar c h-r el at e d tr e at m e nt o n pr o vi si o n of a n a ut h ori z ati o n f or t h e u s e or 
di s cl o s ur e of pr ot e ct e d h e alt h i nf or m ati o n f or s u c h r e s e ar c h. 
2 2. A n y r el e a s e of i nf or m ati o n c arri e s wit h it t h e p ot e nti al f or a n u n a ut h ori z e d r e di s cl o s ur e b y 
t h e R e ci pi e nt a n d t h e i nf or m ati o n m a y n ot b e pr ot e ct e d b y f e d er al l a w. 
2 3. T h e a ut h ori z ati o n s h all b e i n v ali d if u s e d f or a n y ot h er p ur p o s e ot h er t h a n t h e d e s cri b e d 
p ur p o s e f or w hi c h t h e di s cl o s ur e i s m a d e. 
2 4. A p h ot o c o p y of t hi s a ut h ori z ati o n m a y s er v e a s a n ori gi n al. 
 
 
P ati e nt’ s Si g n at ur e 
D at e 
 
 
P er s o n al R e pr e s e nt ati v e’ s Si g n at ur e (if n e c e s s ar y)  
D at e 
 
If it i s n e c e s s ar y f or a p er s o n al r e pr e s e nt ati v e t o si g n a n d d at e t hi s a ut h ori z ati o n d u e t o l a c k 
of c a p a cit y of t h e p ati e nt, i n cl u di n g mi n orit y, i nt er di cti o n or a n y ot h er l e g al r e a s o n, i n di c at e 
b el o w h o w t h e p er s o n si g ni n g a s r e pr e s e nt ati v e h a s a ut h orit y t o d o s o: 
  T h e c o urt a p p oi nt e d p er s o n a cti n g f or t h e p ati e nt, if o n e h a s b e e n a p p oi nt e d. 
 A n a g e nt a cti n g p ur s u a nt t o a v ali d m a n d at e, s p e cifi c all y a ut h ori zi n g t h e a g e nt t o m a k e 
h e alt h c ar e d e ci si o n s. 
 T h e p ati e nt’ s s p o u s e n ot j u di ci all y s e p ar at e d. 
 A n a d ult c hil d of t h e p ati e nt. 
  A n y p ar e nt, w h et h er a d ult or mi n or, f or hi s mi n or c hil d. 
 T h e p ati e nt’ s si bli n g. 
 T h e p ati e nt’ s ot h er a s c e n d a nt s or d e s c e n d a nt s. 
 A n y p er s o n t e m p or aril y st a n di n g i n f or t h e p ar e nt s, w h et h er f or m all y s er vi n g or n ot, f or a 
mi n or u n d er hi s c ar e a n d a n y g u ar di a n f or hi s w ar d. 
 Ot h er ( Pl e a s e s p e cif y):   
 
F or Offi c e U s e O nl y: 
D at e c o p y of a ut h ori z ati o n gi v e n t o p ati e nt   
 
D at e c o p y of a ut h ori z ati o n m ail e d t o p ati e nt   
   
D at e r e c or d s s e nt 
R e vi s e d: 1 1/ 0 4 

Page 1 of 21 
Version Date: 02/14/2020 
 
 
 
 
CONSENT FORM 
 
Title of Research: 
South-seq: DNA sequencing for newborn nurseries in the South 
(NIH Grant Number 2U01HG007301-05) 
 
Site: 
Children’s Hospital 200 Henry Clay Ave., New Orleans, LA 70118 
UAB IRB Protocol #: 
IRB-300000328 
Principal Investigators: 
Jessica Patrick-Esteve, MD 
Sponsor: 
NIH National Human Genome Research Institute 
(Contact: Lucia Hindorff PhD, MPH) 
UAB IRB 
Approved 
04-Mar-2020 
until 
27-Aug-2020 
 
 
Purpose of the Research 
We are asking you to take part in a research study. The purpose of this research study is to use 
whole genome sequencing (WGS), looking at your DNA, to identify the genetic cause of conditions 
like those observed in your child. For individuals with rare, undiagnosed diseases and their families, 
this experimental genetic test may provide information about what is causing the disease or 
condition. This information may be beneficial to your family in directing your child’s health care, 
medical treatments, and your family planning decisions. Educational tools about your child’s 
condition may also become available with a confirmed genetic diagnosis. 
 
In addition, due to the limited number of genetic counselors available to support patients that may 
benefit from WGS, we will be comparing two results delivery methods: genetic counselors (standard 
of care), and healthcare providers (e.g. neonatologists and neonatology nurse practitioners) who 
undergo specific genetics results delivery training. In this clinical trial, we aim to demonstrate that 
both delivery methods are equivalent (i.e. there is no difference between the two methods). 
 
Due to the experimental nature of this research study, data generated is based upon the knowledge 
currently accepted in the field. As more genomes are sequenced and as sequencing techniques 
improve, we will be better at identifying and understanding extremely rare variants (rare changes in 
DNA). In doing this, we will also improve and we will learn more about how certain variants may 
cause disease. For this reason, we plan to store samples for future research. 
There will be approx. 1500 newborn participants enrolled for WGS and 800 parents and/or caregivers 
enrolled for the clinical trial across 5 NICU sites: UAB/Children’s of Alabama, University of Mississippi 
Medical Center (UMMC), Woman’s Hospital, University of Louisville and Norton Health (UofL) and 
Children’s Hospital New Orleans. Samples will also be collected from biological mothers and fathers 
(up to 2,250 individuals), when available, so that we can use their samples to determine inheritance 
of any variants we find in their child. We also hope to include a diverse group of participants so we 
For Children (persons under 18 years of age) participating in this study, the term “You” addresses both 
the participant ("you") and the parent or legally authorized representative ("your child"). 

Page 2 of 21 
Version Date: 02/14/2020 
 
are planning to offer this test to all populations, especially those underrepresented in science and 
genomic research such as African Americans and those from rural areas. 
Explanation of Procedures 
If you agree to join the study, you are agreeing to: 
● Give us permission to collect a blood sample for DNA analysis 
o Adults will give approximately 8mL (approx. 1.6 tsp) of blood that will be drawn from 
the arm. 
o Newborns will give no more than the maximum amount allowed for their body weight 
according to the Children’s Of Alabama guidelines. 
● Give us permission to fully analyze your DNA (or other related material, like RNA or 
protein) and determine the health significance of your genetic results. 
● Allow us to return health information to you that we feel may be important to your child’s 
health or other biological relatives. 
● Allow key study personnel to access your child’s personal medical records to aid in analysis. 
Study personnel may collect information about the child’s symptoms, health history, 
medications/treatments, etc. 
● Provide key study personnel with information about your child’s health history, pregnancy and 
birth history, information about your health and that of other family members, if you know it, 
etc. Study personnel will not access your medical record. They will only have access to the 
information that you choose to share with them. 
● Allow us, if you so choose, to return genetic results that are not related to your child’s 
condition but are medically important for other reasons. 
● Answer survey questions at the time of consent, return of results (ROR), 1-month post ROR, 4- 
months post ROR, and 4.5-months post ROR that will take approximately 20-35 minutes to 
complete. 
You will be asked to take part in two clinic visits here in the nursery or at the outpatient clinic. 
During the first visit, you will be asked to enroll in the study and give a blood sample (1.5hrs) and 
during the second visit you will receive the results of your child’s DNA test either by a genetic 
counselor or a trained healthcare provider (1.5-2hrs). The return of results visit can either take 
place in-person or over the phone. A certified letter with results will be sent to those who do not 
participate in either in the in-person or phone ROR appointment. 
 
More than one parent/guardian/caregiver of a child receiving WGS can participate in the study. It is 
important that anyone participating in the survey portion of the study be present at ROR and 
complete every survey. 
 
Collecting samples from both biological parents increases the chances of identifying genetic 
variation in your child that might be causing his or her symptoms. However if both parents are not 
available, we can still analyze eligible patients and potentially find valuable information. In cases 
where we enroll family members, our DNA test can identify whether a person is the biological 
parent or not. We will not tell you or your family members if we find out that one or both parents 

Page 3 of 21 
Version Date: 02/14/2020 
 
are not biologically related to the child, however we are less likely to discover diagnostic 
information about your condition without both biological parents. 
Your blood samples will be labeled with a unique code (coded) and sent to researchers at the 
HudsonAlpha Institute for Biotechnology, a non-profit genetics research center located in 
Huntsville, AL. Some relevant, health information will also be given to the research staff, and 
coded with a unique study identifier, to aid in their analysis. 
 
We will use state-of-the-art technologies to generate large amounts of information about the DNA 
from you and your child. A group of experts, including medical doctors and researchers, will use 
scientific findings and genetic databases to help decide what genetic information may be 
important to the health of your child. The sequence of all results believed to be medically relevant 
or important to your child’s or your own health will be validated at HudsonAlpha Clinical Services 
Laboratory in Huntsville, AL or another independent clinical laboratory. We expect the entire DNA 
analysis process to take 2-4 months. 
 
We do intend to perform analysis of each sample within our budgetary and technical means. If we 
are unable to analyze your samples you will be notified within 6 months of enrollment and sample 
collection. There is no cause for concern if you are told that we could not complete the analysis 
and provide you with results. 
 
Return of results is at the discretion of the clinicians and researchers involved with this study. If 
they identify results that may impact your child’s health, they may return those results to you. You 
will be scheduled for an appointment to discuss these findings with a genetic counselor or trained 
healthcare provider. Only a subset of results believed to be important to your child’s medical care 
or those in line with the goals of this study will be reported to you. We will not provide you with 
all of the genetic information that we generate. At your results appointment, you may be provided 
with information regarding: 
● Primary findings - These findings will include information about a variant(s) (DNA change) 
that may potentially be the reason for your child’s phenotype (symptoms) or condition. 
o Most children will not receive a primary finding (or diagnosis). If no diagnosis is 
found, we will tell you. Even if we do not find a genetic diagnosis, your condition 
may still be the result of a change in your DNA that we are currently unable to 
identify. 
o If you receive a genetic diagnosis, this may not change your child’s prognosis or 
medical treatment. However it may help you and your doctor to better understand 
the cause of your child’s condition and the risks of similar conditions affecting your 
biological children. 
● Secondary findings – These findings may be reported to any study participant and may 
include any genetic changes that might impact your health or the health of your current or 
future children. These may include: 
o Whether there are any changes in your DNA that could put you at a higher risk for 
developing a disease unrelated to your child’s condition in the future, such as cancer 
or heart disease. 

Page 4 of 21 
Version Date: 02/14/2020 
 
1. Some of these diseases may be medically useful and some may not be 
medically useful. We will not return results that are not medically useful. 
2. Some of these diseases will appear in childhood and others will appear 
when you are an adult. 
● Carrier status – In the event that we discover that your child’s symptoms are caused by a 
recessive genetic condition where he or she inherited one variant (DNA change) from each 
parent, we may provide information about whether or not you are a "carrier" for a genetic 
change that may be passed on to your biological children. 
We will arrange for a genetic counselor or a trained healthcare provider to discuss the results of 
the test with you. Educational materials will also be made available to you to help you better 
understand any results that you may or may not receive as part of this study. 
You will be actively enrolled in this study for up to one year however we may continue to access 
your medical record for up to 5 years. We plan to use coded information from our medical record 
to determine the impact of whole genome sequencing and genetic diagnosis on medical care. 
After you receive the results of the genetic test, you may be contacted by your physician or key 
study personnel to check on you or to ask follow-up questions. Your DNA samples may be stored 
indefinitely for future research unless you choose to withdraw from the study. Please note that 
participation in this study is voluntary and you may withdraw from this study at any time. 
You will also be presented with a baseline survey at the time of enrollment that you can complete 
online using Genome Gateway. The survey will ask you questions about basic demographics, how 
you feel about your child’s health and your experience in the hospital, how well you understand 
medical terms, math and genetics. After you receive results from this testing, you will be asked 
some of these same questions and some additional ones related to your health, your 
understanding of the genetic results returned, and how the results influence future life planning at 
1-month post ROR, 4-months post ROR, and 4.5 months post ROR. 
 
Risks and Discomforts 
The risks of drawing blood include pain, bruising, lightheadedness, and fainting. Infection at the site 
of the needle stick is a rare side effect. These are the same risks you face any time you have a blood 
test. 
 
The main concerns associated with genetic testing are anxiety, depression, or other forms of 
emotional distress that may result from receiving genetic information about the suspected cause of 
your child’s condition. This is especially true for those diseases that are not treatable or preventable. 
Though some treatments have been shown to help individuals with certain genetic conditions, there 
is no "cure" for most. 
 
When performing genetic testing, it may be discovered that family relationships are not as 
predicted. For example, a child might not be biologically related to his/her father, or two people who 
are married might turn out to be biologically related. These findings will not be disclosed as part of 
this study. 

Page 5 of 21 
Version Date: 02/14/2020 
 
In some cases, you may receive information about your carrier status and/or changes in your DNA 
that may impact your health. These findings will only be returned if they were inherited by your child 
who is enrolled in this study and suspected to contribute to their condition. Genetic changes in 
children that affect development may be inherited from one or both parents, even if the parents 
appear to be healthy. This information may affect the way you view or evaluate yourself or your 
family. It may also influence, or generate anxiety about, future family planning decisions. 
It is also important to keep in mind that you and your biological relatives have similar DNA 
sequences. This means that genetic information about your child may also have implications for your 
relatives if the variation was inherited. 
You may be referred to an additional physician or clinic for further testing or advice depending on 
the type of genetic information we generate from your sample. If you experience psychological 
distress or other difficulties, we can also refer you to an appropriate resource for care and/or 
support. 
 
There may be unforeseeable risks associated with receiving genetic information and the potential 
decisions, actions, or inactions that may be required in response to that information. Please consider 
this carefully and ask any questions that you may have before deciding whether or not to participate 
in this study. 
 
It is important that you consider the risks and uncertainties of this research study that make it 
different from traditional medical testing. 
 
We will make sure that the information that you are given is as accurate as possible to the best of 
our ability. We will use the best standards, practices, and technologies available to researchers. 
However, the technologies available to analyze DNA and our knowledge of how DNA affects health 
are changing rapidly. They are also subject to much uncertainty. Some DNA changes that are 
important to health may be missed, and other DNA changes that are not important may be 
incorrectly identified as if they are important. There are also moral and ethical questions about using 
genetic information on which scientific and medical communities have not yet reached a consensus. 
Therefore, we do NOT guarantee that our test will have the same levels of completeness, accuracy, 
or standardization associated with more traditional medical tests. 
 
Before offering your consent to participate in this research study, please consider all of the risks 
associated with: 
● The return or possible lack of return of results; 
● Whether our interpretation of those results is accurate; 
● How you and/or your family will choose to act upon or not act upon the information or lack 
of information. 

Page 6 of 21 
Version Date: 02/14/2020 
 
Benefits 
You may not benefit directly from taking part in this study. However, your participation may lead to 
new discoveries that help to advance medical research and improve patient care, especially, but not 
only, newborn patient care in the future. Your participation in this study may help to make health 
care and access to health care broader and more representative. 
You may find out if there is a change in your child’s DNA that has altered their development. You 
might also find out if this change could affect future biological children. 
A genetic diagnosis may help you connect with other families in the community who face similar 
medical problems. While unlikely, it is possible that a genetic diagnosis may point your doctor to a 
better medical and/or educational treatment. 
You may discover that you or your child are at an increased risk for developing other diseases and 
that information may be of medical benefit. 
 
None of the above benefits are guaranteed, and it is expected that many participants will not receive 
specific information that is relevant to their health. 
 
Alternatives 
This is not a treatment study. Your alternative is not to participate in this research study. 
 
Confidentiality 
Information obtained about you for this study will be kept confidential to the extent allowed by law. 
However, research information that identifies you may be shared with people or organizations for 
quality assurance or data analysis, or with those responsible for ensuring compliance with laws and 
regulations related to research. They include: 
● the UAB Institutional Review Board (IRB). An IRB is a group that reviews the study to protect 
the rights and welfare of research participants. 
● Louisiana State University Health Sciences Center-New Orleans IRB 
● Children’s Hospital New Orleans IRB 
● the NIH National Human Genome Research Institute (NHGRI) 
● the Office for Human Research Protections (OHRP) 
 
The information from the research including your child’s clinical information, family history, and 
genetic variants may be published for scientific purposes; however, your identity will not be given out 
to anyone outside of the clinical team involved with the study. 
 
Your consent form will be placed in your child’s medical record at Children’s Hospital New Orleans. 
This may include either a paper medical record or electronic medical record (EMR). An EMR is an 
electronic version of a paper medical record of your care within this health system. Your child’s EMR 
may indicate that you and your child are enrolled in this study and provide the name and contact 
information for the principal investigator. 

Page 7 of 21 
Version Date: 02/14/2020 
 
Results of research tests or procedures that have been clinically validated (i.e. Sanger reports) may be 
placed in your child’s medical record. All information within your medical record can be viewed by 
individuals authorized to access the record. 
Information relating to this study, including your name, medical record number, date of birth and 
social security number, may be shared with the billing offices of Children’s Hospital New Orleans so 
costs for clinical services can be appropriately paid for by either the study account or by your 
insurance. 
This research is covered by a Certificate of Confidentiality from the National Institutes of Health. The 
researchers with this Certificate may not disclose or use information, documents, or biospecimens 
that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other 
action, suit, or proceeding, or be used as evidence, for example, if there is a court subpoena, unless 
you have consented for this use. Information, documents, or biospecimens protected by this 
Certificate cannot be disclosed to anyone else who is not connected with the research except, if there 
is a federal, state, or local law that requires disclosure (such as to report child abuse or communicable 
diseases but not for federal, state, or local civil, criminal, administrative, legislative, or other 
proceedings, see below); if you have consented to the disclosure, including for your medical 
treatment; or if it is used for other scientific research, as allowed by federal regulations protecting 
research subjects. 
A federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes it illegal 
for health insurance companies, group health plans, and some employers to discriminate against you 
based on your genetic information. This law generally will protect you in the following ways: 
● Health insurance companies and group health plans may not request your genetic information 
that we get from this research. 
● Health insurance companies and group health plans may not use your genetic information 
when making decisions regarding your eligibility or premiums. 
● Employers with 15 or more employees may not use your genetic information that we get from 
this research when making a decision to hire, promote, or fire you or when setting the terms 
of your employment. 
 
Be aware this federal law does not protect you against genetic discrimination by companies that sell 
life insurance, disability insurance, or long-term care insurance, nor does it protect you against 
genetic discrimination by some employers. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this Web site at any time. 
 
Louisiana law prohibits discrimination in employment or insurability based on your genetic 
information. Your genetic information is considered your property and no insurer or employer may 
obtain genetic information or a DNA sample without first obtaining your written consent. (LA Statute 
RS22:1023 and RS23:368). 

Page 8 of 21 
Version Date: 02/14/2020 
 
Voluntary Participation and Withdrawal 
Whether or not you take part in this study is your choice. There will be no penalty if you decide not to 
be in the study. If you decide not to be in the study, you will not lose any benefits you are otherwise 
owed. You are free to withdraw from this research study at any time. Your choice to leave the study 
will not affect your relationship with any institution participating in this study. 
In the event that you chose to withdraw from the study: 
● No further genetic information from the study will be reported to you. 
● Your blood samples will be destroyed. 
● You will not be contacted to provide new information, additional samples, or 
participate in additional studies related to this project. 
● If the analysis of your DNA has been completed, this information will be retained for the 
study. 
If you would like to withdraw from the study, please contact Dr. Patrick-Esteve at 504-896-9418. 
 
Cost of Participation 
There will be no cost to you for taking part in this study. The blood draw, genomic sequencing and 
analysis, and genetic counseling related to this study will be provided to you at no cost during the 
study period. 
 
After you receive your research results, you may decide with your doctor or your child’s doctor to 
get more testing. The costs of your standard medical care or any services rendered in response to a 
genetic finding identified by this research project will be billed to you and/or your insurance 
company in the usual manner. This type of follow-up medical testing will be considered part of your 
clinical care, and will not be paid for by the research study. 
 
Payment for Participation in Research 
Participation in this study is voluntary and $25 will be provided for each survey completed for a total 
of $125 for your completion of all 5 study-related surveys. Ask the study staff about the method of 
payment that will be used for this study (e.g., check, cash, gift card, direct deposit); payment may 
take up to 4 weeks to process. 
 
Payment for Research-Related Injuries 
UAB, UMMC, HudsonAlpha, UofL, Children’s Hospital New Orleans/LSUHSC-NO, and 
NIH/NHGRI/sponsors of this research project have not provided for any payment if you are harmed as 
a result of taking part in this study. If such harm occurs, treatment will be provided. However, this 
treatment will not be provided free of charge. 
 
Significant New Findings 
The study doctor or study staff will tell you if new information becomes available that might affect 
your choice to stay in the study. Please note that HudsonAlpha may, but is not required to, reanalyze 
your sample or report any new findings after results have been returned. 

Page 9 of 21 
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Storage of Specimens for Future Use 
As part of this study, we would like to store some of the blood and DNA specimens collected from 
you and your child for validation of variants (to determine if a variant was inherited from a parent, 
etc.) identified by this project and for future research relevant to rare disease or other genetic 
disorders. The future research may be conducted by the study doctor or by other researchers that 
obtain IRB approval for their research. The specimens will be labeled with a code that only the study 
doctor can link back to you. Results of any future research will not be given to you or your doctor. The 
specimens obtained from you in this research may help in the development of a future commercial 
product. There are no plans to provide financial compensation to you should this occur. You do not 
have to agree to allow your specimens to be stored in order to be part of this study. 
You may at any time withdraw from the study and request that your specimens be removed from 
storage and not be used for future research. If you decide you want your specimens removed, you 
may contact Dr. Bruce Korf at 205-934-9411. Once the request is received, and if your samples have 
not already been used for other research, they will be destroyed. If you do not make such a request, 
your specimens will be stored indefinitely or until used. 
Initial next to your choice below: 
 
 
I agree to allow my specimens to be kept in the HudsonAlpha CSL and used for future genetics 
research. 
 
 
I do NOT agree to allow my specimens to be kept and used for future research. 
 
Genomic Data Sharing (GDS) 
We consider the privacy of your information to be of high priority and will take a variety of steps to 
ensure that privacy. However, it is important for researchers to share some of the information that 
they learn from studying human samples. We will never share personally identifiable information, 
like names and addresses, with anyone outside of the research study. However, parts of your 
information may be shared. 
 
Some of your genetic information, limited to a very small subset that will not cause privacy loss risks 
to you, may be published in scientific journals or other unrestricted-access public venues to 
encourage sharing of the knowledge that may be learned by analyzing your DNA and DNA from other 
individuals. This could include information about your child’s symptoms, their age, and any genetic 
findings that we discover. 
 
We may share coded lists of the DNA differences that we identify in public genetic databases. These 
databases gather genetic information from large groups of people and are pooled together such that 
no specific participant can be identified. 
 
There is a very small chance that some commercial value may result from the use of your donated 
samples or genetic information. If that happens, you will not receive a share in any profits. 

Page 10 of 21 
Version Date: 02/14/2020 
 
Unless you opt out, we may submit your complete genomic data along with some of your coded 
health information to an NIH-designated Data Repository such as dbGAP 
(http://www.ncbi.nlm.nih.gov/gap) , AnVIL (https://anvilproject.org/), or another controlled access 
database. Access to dbGAP is only available to qualified researchers at qualified institutions who 
have agreed to abide by certain privacy safeguards, obligating them, both legally and ethically, to 
protect your privacy and to maintain information confidentiality. However, since your genetic 
information is unique to you, there is a small chance that someone could trace your information back 
to you. This risk is very small, but may grow in the future. Some risks and benefits are listed below: 
Risks: The risk of sharing your genomic data is that someone could link the information stored 
in the databases back to you. If your information suggests something about your health such 
as increased risk for disease, it could be misused. For example, it could be used to make it 
harder for you to get or keep a job or insurance or be used to discriminate against you or your 
family. There may also be other unknown risks. As stated above (confidentiality section of this 
form), there are federal protections against the misuse of your data (i.e. the Genetic 
Information Nondiscrimination Act, GINA). 
Benefits: There is no direct benefit to you from sharing your genomic data with NIH- 
designated repositories, however allowing researchers to use your data may lead to a better 
understanding of how genes affect health which may help other people in the future. 
 
Initial next to your choice below: 
 
 
 I agree for my genetic and other relevant study data, such as health information, to be shared 
with NIH-designated repositories such as dbGAP and AnVIL in a coded form for future research 
or analysis 
 
 I do NOT agree for my genetic and other relevant study data, such as health information, to be 
shared with NIH-designated repositories such as dbGAP and AnVIL in a coded form for future 
research or analysis 
 
Contact For Future Research 
As new research opportunities are identified, the researchers may wish to perform additional tests 
on fresh samples or invite eligible participants to enroll in new studies. We would like permission to 
contact you in the future, however this is not a requirement to participate in this study. A separate 
consent form will be obtained if you wish to participate in future research. 
 
Initial next to your choice below: 
 
 
 
You have permission to contact me about new research opportunities that may interest me. 
 
 
 
You do NOT have permission to contact me about new research opportunities. 

Page 11 of 21 
Version Date: 02/14/2020 
 
Secondary Findings 
One unanimous decision to receive or not to receive secondary findings must be made by each 
participant family. Because parental samples are only used for confirmation of variation identified in 
the child’s whole genome sequence for this project, only those secondary findings identified in the 
child will be confirmed in the parental samples. Participant families may opt to receive this 
information, if available. If a family chooses to do so, information about an identified secondary 
finding will be included in the child’s medical record. Nothing will be placed in the parent’s medical 
record. 
 
Initial next to your choice below: 
 
 
 
 We (child and parent(s), if enrolled) would like to receive information about secondary 
findings. 
 
 
 
 We (child and parent(s), if enrolled) would NOT like to receive information about secondary 
findings. 
 
Questions 
If you have any questions, concerns, or complaints about the research or a research-related injury 
including available treatments, please contact Dr. Bruce Korf at 205-934-9411 or Dr. Patrick-Esteve at 
504-896-9418. 
 
If you have questions about your rights as a research participant, or concerns or complaints about the 
research, you may contact, Dr. Patrick-Esteve, at Children’s Hospital, 200 Henry Clay Ave., New 
Orleans, LA 70118, jpatri@lsuhsc.edu, 504-896-9418. You may also contact the Chancellor of the LSU 
Health Sciences Center of New Orleans at (504) 568-4801 and Dr. Druby Hebert, Chairman of the 
Children’s Hospital New Orleans IRB, at 504-899-9511. 
 
Legal Rights 
You are not waiving any of your legal rights by signing this consent form. 

Page 12 of 21 
Version Date: 02/14/2020 
 
Signatures 
Your signature below indicates that you have read (or been read) the information 
provided above and agree to have your child participate in this study. You will receive a copy of this 
signed consent form. 
Your signature below indicates that you have read (or been read) the information provided above 
and agree to participate in this study. You will receive a copy of this signed consent form. 
 
 
Name of Proband Child (printed) 
 
 
Signature of Parent or Legally Authorized Representative 
Date 
 
 
 
Mother/Father/Caregiver 
Name of Parent Participant (printed) 
Relationship 
 
 
Signature of Parent Participant 
Date 
 
Mother/Father/Caregiver 
Name of Parent Participant (printed) 
Relationship 
 
 
Signature of Parent Participant 
Date 
 
 
 
 
Signature of Person Obtaining Consent 
Date 
 
In this research study, one consent form may be used to waive consent for the infant and capture 
informed consent of both parents; however, a separate HIPPA Authorization form will be completed 
for each participant. 
 
 
Waiver of Assent 
 
The assent of   
 
 
(name of child/minor) was waived because of: 
Age  
 
Maturity  
 
 Psychological state of the child  
 

Page 13 of 21 
Version Date: 02/14/2020 
 
LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER 
At New Orleans (LSUHSC-NO) and CHILDREN’S HOSPITAL 
INSTITUTIONAL REVIEW BOARD/ADMINISTRATIVE REVIEW COMMITTEE 
 
*********************************************************************************** 
*** 
 
AUTHORIZATION FOR USE AND DISCLOSURE OF PROTECTED HEALTH INFORMATION 
FOR RESEARCH PURPOSES – Proband 
 
Title of Research Project: South-seq: DNA sequencing for newborn nurseries in the South 
 
Name of Sponsor: 
National Institutes of Health (NIH) National Human Genome Research Institute 
If applicable IRB Number: N/A 
Principal Investigator: Jessica Patrick-Esteve, MD 
IRB or Protocol Number: new / ARC #new 
I hereby request and authorize the LSUHSC-NO and/or Children’s Hospital to use and disclose 
protected health information from the record(s) of: 
Patient’s Name/Address: 
 
Birth Date:  
/ 
/ 
 
 
Specifically, I request and authorize any part of my health information relevant to the research 
project, identified above and in the Informed Consent document, to be used and/or disclosed to the 
Principal Investigator identified above or his/her designee, in connection with the research project. 
(NOTE: The following sentence may be deleted if not appropriate): I understand that this may include 
information relating to: Human Immunodeficiency Virus (“HIV”) infection or Acquired 
Immunodeficiency Syndrome (“AIDS”); treatment for or history of drug or alcohol abuse; and/or 
mental or behavioral health or psychiatric care. 
 
I specifically authorize the use and disclosure of the following PHI: 
(Please provide a detailed description of the particular data and period of time you are requesting) 
 
 X Complete health record(s) for date(s) of service from date of birth to 5 years after study 
enrollment, which may contain all of the documents listed below, as well as other notes or 
documents relating to my treatment or hospitalization. 
 
History and physical exam  
 
    Hospital Inpatient Records  
 

Page 14 of 21 
Version Date: 02/14/2020 
 
 
Clinic/Outpatient Records 
 
 
 Consultation reports  
 
 
Laboratory test results 
 
 
Radiology Reports 
 
 
Pathology Reports 
 
 
Discharge Summary 
 
 
Progress Notes 
 
 
Photographs, videotapes 
 
 
X-Ray films/images, digital or other images 
 
 
Diagnosis and Treatment Codes 
 
 
Complete billing record 
 
 
Other:  
 
I understand that copies of the records indicated above will be: 
• Used by employees of LSUHSC-NO and/or Children’s Hospital including treatment providers, 
and/or other members of its workforce. 
 
• Disclosed to LSUHSC-NO and/or Children’s Hospital, government officials or government 
agencies, such as the Food and Drug Administration study sponsors, study monitors, or others 
responsible for oversight of the research project. 
 
• Sent to collaborating researchers outside LSUHSC-NO and/or Children’s Hospital if and to the 
extent indicated in the attached Informed Consent document(s). 
 
I understand that by signing this form, I am allowing LSUHSC-NO and/or Children’s Hospital and their 
researchers to use or disclose my health information in connection with the attached Informed 
Consent and for the purpose of the research that is described in the Informed Consent. For example, 
the researchers may need the information to verify that I am eligible to participate in the study, or to 
monitor the results, including expected or unexpected side effects or outcomes. Other 
University/Hospital and government officials, safety monitors, and study sponsors may need the 
information to ensure that the study is conducted properly. Also, I understand that my health 
information may be disclosed to insurance companies or others responsible for my medical bills in 
order to secure payment. 
 
I understand that any privacy rights not specifically mentioned in this Authorization are contained in 
the Notice of Privacy Practices that I received or will receive from the Principal Investigator or at the 
facility that I attend. 
 
I understand that I may revoke this authorization at any time, except to the extent that LSUHSC-NO 
and/or Children’s Hospital has already relied on the authorization, by sending or transmitting of a 
facsimile, a written notice to the contact person listed in the attached Informed Consent 
document(s). 

Page 15 of 21 
Version Date: 02/14/2020 
 
I understand that if my information already has been included in a research database or registry as 
described in the attached Informed Consent document(s), LSUHSC-NO and/or Children’s Hospital 
considers itself to have relied on it, and therefore my information will not be removed from those 
repositories. Unless otherwise revoked, I understand that this authorization (_X_) will not expire or 
(  ) will expire upon {date or event} 
. I understand that if I do not sign this form, I will 
not be able to participate in the above research study or receive the study-related interventions, but 
that LSUHSC-NO and/or Children’s Hospital cannot otherwise condition treatment on my signing this 
form. 
While the research study is in progress, my right to access any research records or results that are 
maintained by the facility may be suspended until the research study is over. If my access is denied, I 
understand that it will be reinstated at the end of the research study. 
I understand the information disclosed by this authorization may be subject to re-disclosure by the 
recipient and no longer be protected by the Health Insurance Portability and Accountability Act. The 
LSUHSC and/or Children’s Hospital facilities, their employees, officers, and physicians are hereby 
released from any legal responsibility or liability for disclosure of the above information to the extent 
indicated and authorized herein. 
I UNDERSTAND THAT THIS AUTHORIZATION SUPERSEDES ANY CONTRARY INFORMATION IN ANY 
OTHER DOCUMENTS I HAVE SIGNED RELATED TO THE ATTACHED STUDY. 
 
Signature of Patient or Patient’s Legal Representative: 
 
Date: 
/ 
/ 
 
 
Printed Name of Legal Representative (if any): 
 
 
Representative’s Authority to Act for Patient (e.g., relationship to patient): 
 
 
Verification of Representative’s Authority: ( ) viewed driver’s license ( ) viewed Power of Attorney 
( ) viewed other 
(specify) 

Page 16 of 21 
Version Date: 02/14/2020 
 
LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER 
At New Orleans (LSUHSC-NO) and CHILDREN’S HOSPITAL 
INSTITUTIONAL REVIEW BOARD/ADMINISTRATIVE REVIEW COMMITTEE 
 
*********************************************************************************** 
*** 
 
AUTHORIZATION FOR USE AND DISCLOSURE OF PROTECTED HEALTH INFORMATION 
FOR RESEARCH PURPOSES – Biological Mother 
 
Title of Research Project: South-seq: DNA sequencing for newborn nurseries in the South 
 
Name of Sponsor: 
National Institutes of Health (NIH) National Human Genome Research Institute 
If applicable IRB Number: N/A 
Principal Investigator: Jessica Patrick-Esteve, MD 
IRB or Protocol Number: new / ARC #new 
I hereby request and authorize the LSUHSC-NO and/or Children’s Hospital to use and disclose 
protected health information from the record(s) of: 
Patient’s Name/Address: 
 
Birth Date:  
/ 
/ 
 
 
Specifically, I request and authorize any part of my health information relevant to the research 
project, identified above and in the Informed Consent document, to be used and/or disclosed to the 
Principal Investigator identified above or his/her designee, in connection with the research project. 
(NOTE: The following sentence may be deleted if not appropriate): I understand that this may include 
information relating to: Human Immunodeficiency Virus (“HIV”) infection or Acquired 
Immunodeficiency Syndrome (“AIDS”); treatment for or history of drug or alcohol abuse; and/or 
mental or behavioral health or psychiatric care. 
 
I specifically authorize the use and disclosure of the following PHI: 
(Please provide a detailed description of the particular data and period of time you are requesting) 
 
 X Complete health record(s) for date(s) of service from study enrollment to 5 years after study 
enrollment, which may contain all of the documents listed below, as well as other notes or 
documents relating to my treatment or hospitalization. 
 
History and physical exam 
 
    Hospital Inpatient Records 
 
 
Clinic/Outpatient Records 
 
 
 Consultation reports  
 

Page 17 of 21 
Version Date: 02/14/2020 
 
 
Laboratory test results 
 
 
Radiology Reports 
 
 
Pathology Reports 
 
 
Discharge Summary 
 
 
Progress Notes 
 
 
Photographs, videotapes 
 
 
X-Ray films/images, digital or other images 
 
 
Diagnosis and Treatment Codes 
 
 
Complete billing record 
 
 
Other:  
 
I understand that copies of the records indicated above will be: 
• Used by employees of LSUHSC-NO and/or Children’s Hospital including treatment providers, 
and/or other members of its workforce. 
• Disclosed to LSUHSC-NO and/or Children’s Hospital, government officials or government 
agencies, such as the Food and Drug Administration study sponsors, study monitors, or others 
responsible for oversight of the research project. 
 
• Sent to collaborating researchers outside LSUHSC-NO and/or Children’s Hospital if and to the 
extent indicated in the attached Informed Consent document(s). 
 
I understand that by signing this form, I am allowing LSUHSC-NO and/or Children’s Hospital and their 
researchers to use or disclose my health information in connection with the attached Informed 
Consent and for the purpose of the research that is described in the Informed Consent. For example, 
the researchers may need the information to verify that I am eligible to participate in the study, or to 
monitor the results, including expected or unexpected side effects or outcomes. Other 
University/Hospital and government officials, safety monitors, and study sponsors may need the 
information to ensure that the study is conducted properly. Also, I understand that my health 
information may be disclosed to insurance companies or others responsible for my medical bills in 
order to secure payment. 
 
I understand that any privacy rights not specifically mentioned in this Authorization are contained in 
the Notice of Privacy Practices that I received or will receive from the Principal Investigator or at the 
facility that I attend. 
 
I understand that I may revoke this authorization at any time, except to the extent that LSUHSC-NO 
and/or Children’s Hospital has already relied on the authorization, by sending or transmitting of a 
facsimile, a written notice to the contact person listed in the attached Informed Consent 
document(s). 
 
I understand that if my information already has been included in a research database or registry as 
described in the attached Informed Consent document(s), LSUHSC-NO and/or Children’s Hospital 

Page 18 of 21 
Version Date: 02/14/2020 
 
considers itself to have relied on it, and therefore my information will not be removed from those 
repositories. Unless otherwise revoked, I understand that this authorization (_X_) will not expire or 
(  ) will expire upon {date or event} 
. I understand that if I do not sign this form, I will 
not be able to participate in the above research study or receive the study-related interventions, but 
that LSUHSC-NO and/or Children’s Hospital cannot otherwise condition treatment on my signing this 
form. 
While the research study is in progress, my right to access any research records or results that are 
maintained by the facility may be suspended until the research study is over. If my access is denied, I 
understand that it will be reinstated at the end of the research study. 
I understand the information disclosed by this authorization may be subject to re-disclosure by the 
recipient and no longer be protected by the Health Insurance Portability and Accountability Act. The 
LSUHSC and/or Children’s Hospital facilities, their employees, officers, and physicians are hereby 
released from any legal responsibility or liability for disclosure of the above information to the extent 
indicated and authorized herein. 
I UNDERSTAND THAT THIS AUTHORIZATION SUPERSEDES ANY CONTRARY INFORMATION IN ANY 
OTHER DOCUMENTS I HAVE SIGNED RELATED TO THE ATTACHED STUDY. 
 
Signature of Patient or Patient’s Legal Representative: 
 
Date: 
/ 
/ 
 
 
Printed Name of Legal Representative (if any): 
 
 
Representative’s Authority to Act for Patient (e.g., relationship to patient): 
 
 
Verification of Representative’s Authority: ( ) viewed driver’s license ( ) viewed Power of Attorney 
( ) viewed other 
(specify) 

Page 19 of 21 
Version Date: 02/14/2020 
 
LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER 
At New Orleans (LSUHSC-NO) and CHILDREN’S HOSPITAL 
INSTITUTIONAL REVIEW BOARD/ADMINISTRATIVE REVIEW COMMITTEE 
 
*********************************************************************************** 
*** 
 
AUTHORIZATION FOR USE AND DISCLOSURE OF PROTECTED HEALTH INFORMATION 
FOR RESEARCH PURPOSES – Biological Father 
 
Title of Research Project: South-seq: DNA sequencing for newborn nurseries in the South 
 
Name of Sponsor: 
National Institutes of Health (NIH) National Human Genome Research Institute 
If applicable IRB Number: N/A 
Principal Investigator: Jessica Patrick-Esteve, MD 
IRB or Protocol Number: new / ARC #new 
I hereby request and authorize the LSUHSC-NO and/or Children’s Hospital to use and disclose 
protected health information from the record(s) of: 
Patient’s Name/Address: 
 
 
Birth Date:  
/ 
/ 
 
 
Specifically, I request and authorize any part of my health information relevant to the research 
project, identified above and in the Informed Consent document, to be used and/or disclosed to the 
Principal Investigator identified above or his/her designee, in connection with the research project. 
(NOTE: The following sentence may be deleted if not appropriate): I understand that this may include 
information relating to: Human Immunodeficiency Virus (“HIV”) infection or Acquired 
Immunodeficiency Syndrome (“AIDS”); treatment for or history of drug or alcohol abuse; and/or 
mental or behavioral health or psychiatric care. 
 
I specifically authorize the use and disclosure of the following PHI: 
(Please provide a detailed description of the particular data and period of time you are requesting) 
 
 X Complete health record(s) for date(s) of service from study enrollment to 5 years after study 
enrollment, which may contain all of the documents listed below, as well as other notes or 
documents relating to my treatment or hospitalization. 
 
History and physical exam 
 
    Hospital Inpatient Records 
 
 
Clinic/Outpatient Records 
 
 
 Consultation reports  
 
 
Laboratory test results 
 

Page 20 of 21 
Version Date: 02/14/2020 
 
 
Radiology Reports 
 
 
Pathology Reports 
 
 
Discharge Summary 
 
 
Progress Notes 
 
 
Photographs, videotapes 
 
 
X-Ray films/images, digital or other images 
 
 
Diagnosis and Treatment Codes 
 
 
Complete billing record 
 
 
Other:  
 
I understand that copies of the records indicated above will be: 
• Used by employees of LSUHSC-NO and/or Children’s Hospital including treatment providers, 
and/or other members of its workforce. 
• Disclosed to LSUHSC-NO and/or Children’s Hospital, government officials or government 
agencies, such as the Food and Drug Administration study sponsors, study monitors, or others 
responsible for oversight of the research project. 
 
• Sent to collaborating researchers outside LSUHSC-NO and/or Children’s Hospital if and to the 
extent indicated in the attached Informed Consent document(s). 
 
I understand that by signing this form, I am allowing LSUHSC-NO and/or Children’s Hospital and their 
researchers to use or disclose my health information in connection with the attached Informed 
Consent and for the purpose of the research that is described in the Informed Consent. For example, 
the researchers may need the information to verify that I am eligible to participate in the study, or to 
monitor the results, including expected or unexpected side effects or outcomes. Other 
University/Hospital and government officials, safety monitors, and study sponsors may need the 
information to ensure that the study is conducted properly. Also, I understand that my health 
information may be disclosed to insurance companies or others responsible for my medical bills in 
order to secure payment. 
 
I understand that any privacy rights not specifically mentioned in this Authorization are contained in 
the Notice of Privacy Practices that I received or will receive from the Principal Investigator or at the 
facility that I attend. 
 
I understand that I may revoke this authorization at any time, except to the extent that LSUHSC-NO 
and/or Children’s Hospital has already relied on the authorization, by sending or transmitting of a 
facsimile, a written notice to the contact person listed in the attached Informed Consent 
document(s). 
 
I understand that if my information already has been included in a research database or registry as 
described in the attached Informed Consent document(s), LSUHSC-NO and/or Children’s Hospital 
considers itself to have relied on it, and therefore my information will not be removed from those 

Page 21 of 21 
Version Date: 02/14/2020 
 
repositories. Unless otherwise revoked, I understand that this authorization (_X_) will not expire or 
(  ) will expire upon {date or event} 
. I understand that if I do not sign this form, I will 
not be able to participate in the above research study or receive the study-related interventions, but 
that LSUHSC-NO and/or Children’s Hospital cannot otherwise condition treatment on my signing this 
form. 
While the research study is in progress, my right to access any research records or results that are 
maintained by the facility may be suspended until the research study is over. If my access is denied, I 
understand that it will be reinstated at the end of the research study. 
I understand the information disclosed by this authorization may be subject to re-disclosure by the 
recipient and no longer be protected by the Health Insurance Portability and Accountability Act. The 
LSUHSC and/or Children’s Hospital facilities, their employees, officers, and physicians are hereby 
released from any legal responsibility or liability for disclosure of the above information to the extent 
indicated and authorized herein. 
I UNDERSTAND THAT THIS AUTHORIZATION SUPERSEDES ANY CONTRARY INFORMATION IN ANY 
OTHER DOCUMENTS I HAVE SIGNED RELATED TO THE ATTACHED STUDY. 
 
Signature of Patient or Patient’s Legal Representative: 
 
Date: 
/ 
/ 
 
 
Printed Name of Legal Representative (if any): 
 
 
Representative’s Authority to Act for Patient (e.g., relationship to patient): 
 
 
Verification of Representative’s Authority: ( ) viewed driver’s license ( ) viewed Power of Attorney 
( ) viewed other 
(specify) 

Page 1 of 14 
Version Date: 02/14/2020 
 
 
 
 
CONSENT FORM 
Title of Research: 
South-seq: DNA sequencing for newborn nurseries in the South 
(NIH Grant Number 2U01HG007301-05) 
Site: 
University of Louisville (17.1333) and Norton Healthcare 
UAB IRB Protocol #: 
IRB-300000328 
 
Principal Investigators: 
Kyle Brothers, MD, PhD 
 
Sponsor: 
NIH National Human Genome Research Institute 
(Contact: Lucia Hindorff PhD, MPH) 
UAB IRB 
Approved 
04-Mar-2020 
until 
27-Aug-2020 
 
 
Purpose of the Research 
We are asking you to take part in a research study. The purpose of this research study is to use 
whole genome sequencing (WGS), looking at your DNA, to identify the genetic cause of conditions 
like those observed in your child. For individuals with rare, undiagnosed diseases and their families, 
this experimental genetic test may provide information about what is causing the disease or 
condition. This information may be beneficial to your family in directing your child’s health care, 
medical treatments, and your family planning decisions. Educational tools about your child’s 
condition may also become available with a confirmed genetic diagnosis. 
 
In addition, due to the limited number of genetic counselors available to support patients that may 
benefit from WGS, we will be comparing two results delivery methods: genetic counselors (standard 
of care), and healthcare providers (e.g. neonatologists and neonatology nurse practitioners) who 
undergo specific genetics results delivery training. In this clinical trial, we aim to demonstrate that 
both delivery methods are equivalent (i.e. there is no difference between the two methods). 
 
Due to the experimental nature of this research study, data generated is based upon the knowledge 
currently accepted in the field. As more genomes are sequenced and as sequencing techniques 
improve, we will be better at identifying and understanding extremely rare variants (rare changes in 
DNA). In doing this, we will also improve and we will learn more about how certain variants may 
cause disease. For this reason, we plan to store samples for future research. 
There will be approx. 1500 newborn participants enrolled for WGS and 800 parents and/or caregivers 
enrolled for the clinical trial across 4 NICU sites: UAB/Children’s of Alabama, University of Mississippi 
Medical Center (UMMC), Woman’s Hospital, University of Louisville and Norton Healthcare (UofL). 
Samples will also be collected from biological mothers and fathers (up to 2,250 individuals), when 
available, so that we can use their samples to determine inheritance of any variants we find in their 
child. We also hope to include a diverse group of participants so we are planning to offer this test to 
For Children (persons under 18 years of age) participating in this study, the term “You” addresses both 
the participant ("you") and the parent or legally authorized representative ("your child"). 

Page 2 of 14 
Version Date: 02/14/2020 
 
all populations, especially those underrepresented in science and genomic research such as African 
Americans and those from rural areas. 
Explanation of Procedures 
If you agree to join the study, you are agreeing to: 
● Give us permission to collect a blood sample for DNA analysis 
o Adults will give approximately 8mL (approx. 1.6 tsp) of blood that will be drawn from 
the arm. 
o Newborns will give no more than the maximum amount allowed for their body weight 
according to the University of Louisville and Norton Children’s Hospital guidelines. 
● Give us permission to fully analyze your DNA (or other related material, like RNA or 
protein) and determine the health significance of your genetic results. 
● Allow us to return health information to you that we feel may be important to your child’s 
health or other biological relatives. 
● Allow key study personnel to access your child’s personal medical records to aid in analysis. 
Study personnel may collect information about the child’s symptoms, health history, 
medications/treatments, etc. 
● Provide key study personnel with information about your child’s health history, pregnancy and 
birth history, information about your health and that of other family members, if you know it, 
etc. Study personnel will not access your medical record. They will only have access to the 
information that you choose to share with them. 
● Allow us, if you so choose, to return genetic results that are not related to your child’s 
condition but are medically important for other reasons. 
● Answer survey questions at the time of consent, return of results (ROR), 1-month post ROR, 4- 
months post ROR, and 4.5-months post ROR that will take approximately 20-35 minutes to 
complete. 
You will be asked to take part in two clinic visits here in the nursery or at the outpatient clinic. 
During the first visit, you will be asked to enroll in the study and give a blood sample (1.5hrs) and 
during the second visit you will receive the results of your child’s DNA test either by a genetic 
counselor or a trained healthcare provider (1.5-2hrs). The return of results visit can either take 
place in-person or over the phone. A certified letter with results will be sent to those who do not 
participate in either in the in-person or phone ROR appointment. 
 
More than one parent/guardian/caregiver of a child receiving WGS can participate in the study. It is 
important that anyone participating in the survey portion of the study be present at ROR and 
complete every survey. 
 
Collecting samples from both biological parents increases the chances of identifying genetic 
variation in your child that might be causing his or her symptoms. However if both parents are not 
available, we can still analyze eligible patients and potentially find valuable information. In cases 
where we enroll family members, our DNA test can identify whether a person is the biological 
parent or not. We will not tell you or your family members if we find out that one or both parents 
are not biologically related to the child, however we are less likely to discover diagnostic 
information about your condition without both biological parents. 

Page 3 of 14 
Version Date: 02/14/2020 
 
Your blood samples will be labeled with a unique code (coded) and sent to researchers at the 
HudsonAlpha Institute for Biotechnology, a non-profit genetics research center located in 
Huntsville, AL. Some relevant, health information will also be given to the research staff, and 
coded with a unique study identifier, to aid in their analysis. 
 
We will use state-of-the-art technologies to generate large amounts of information about the DNA 
from you and your child. A group of experts, including medical doctors and researchers, will use 
scientific findings and genetic databases to help decide what genetic information may be 
important to the health of your child. The sequence of all results believed to be medically relevant 
or important to your child’s or your own health will be validated at HudsonAlpha Clinical Services 
Laboratory in Huntsville, AL or another independent clinical laboratory. We expect the entire DNA 
analysis process to take 2-4 months. 
 
We do intend to perform analysis of each sample within our budgetary and technical means. If we 
are unable to analyze your samples you will be notified within 6 months of enrollment and sample 
collection. There is no cause for concern if you are told that we could not complete the analysis 
and provide you with results. 
 
Return of results is at the discretion of the clinicians and researchers involved with this study. If 
they identify results that may impact your child’s health, they may return those results to you. You 
will be scheduled for an appointment to discuss these findings with a genetic counselor or trained 
healthcare provider. Only a subset of results believed to be important to your child’s medical care 
or those in line with the goals of this study will be reported to you. We will not provide you with 
all of the genetic information that we generate. At your results appointment, you may be provided 
with information regarding: 
● Primary findings - These findings will include information about a variant(s) (DNA change) 
that may potentially be the reason for your child’s phenotype (symptoms) or condition. 
o Most children will not receive a primary finding (or diagnosis). If no diagnosis is 
found, we will tell you. Even if we do not find a genetic diagnosis, your condition 
may still be the result of a change in your DNA that we are currently unable to 
identify. 
o If you receive a genetic diagnosis, this may not change your child’s prognosis or 
medical treatment. However it may help you and your doctor to better understand 
the cause of your child’s condition and the risks of similar conditions affecting your 
biological children. 
● Secondary findings – These findings may be reported to any study participant and may 
include any genetic changes that might impact your health or the health of your current or 
future children. These may include: 
o Whether there are any changes in your DNA that could put you at a higher risk for 
developing a disease unrelated to your child’s condition in the future, such as cancer 
or heart disease. 
1. Some of these diseases may be medically useful and some may not be 
medically useful. We will not return results that are not medically useful. 

Page 4 of 14 
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2. Some of these diseases will appear in childhood and others will appear 
when you are an adult. 
● Carrier status – In the event that we discover that your child’s symptoms are caused by a 
recessive genetic condition where he or she inherited one variant (DNA change) from each 
parent, we may provide information about whether or not you are a "carrier" for a genetic 
change that may be passed on to your biological children. 
We will arrange for a genetic counselor or a trained healthcare provider to discuss the results of 
the test with you. Educational materials will also be made available to you to help you better 
understand any results that you may or may not receive as part of this study. 
You will be actively enrolled in this study for up to one year however we may continue to access 
your medical record for up to 5 years. We plan to use coded information from our medical record 
to determine the impact of whole genome sequencing and genetic diagnosis on medical care. 
After you receive the results of the genetic test, you may be contacted by your physician or key 
study personnel to check on you or to ask follow-up questions. Your DNA samples may be stored 
indefinitely for future research unless you choose to withdraw from the study. Please note that 
participation in this study is voluntary and you may withdraw from this study at any time. 
You will also be presented with a baseline survey at the time of enrollment that you can complete 
online using Genome Gateway. The survey will ask you questions about basic demographics, how 
you feel about your child’s health and your experience in the hospital, how well you understand 
medical terms, math and genetics. After you receive results from this testing, you will be asked 
some of these same questions and some additional ones related to your health, your 
understanding of the genetic results returned, and how the results influence future life planning at 
1-month post ROR, 4-months post ROR, and 4.5 months post ROR. 
 
Risks and Discomforts 
The risks of drawing blood include pain, bruising, lightheadedness, and fainting. Infection at the site 
of the needle stick is a rare side effect. These are the same risks you face any time you have a blood 
test. 
 
The main concerns associated with genetic testing are anxiety, depression, or other forms of 
emotional distress that may result from receiving genetic information about the suspected cause of 
your child’s condition. This is especially true for those diseases that are not treatable or preventable. 
Though some treatments have been shown to help individuals with certain genetic conditions, there 
is no "cure" for most. 
 
When performing genetic testing, it may be discovered that family relationships are not as 
predicted. For example, a child might not be biologically related to his/her father, or two people who 
are married might turn out to be biologically related. These findings will not be disclosed as part of 
this study. 
 
In some cases, you may receive information about your carrier status and/or changes in your DNA 
that may impact your health. These findings will only be returned if they were inherited by your child 

Page 5 of 14 
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who is enrolled in this study and suspected to contribute to their condition. Genetic changes in 
children that affect development may be inherited from one or both parents, even if the parents 
appear to be healthy. This information may affect the way you view or evaluate yourself or your 
family. It may also influence, or generate anxiety about, future family planning decisions. 
It is also important to keep in mind that you and your biological relatives have similar DNA 
sequences. This means that genetic information about your child may also have implications for your 
relatives if the variation was inherited. 
You may be referred to an additional physician or clinic for further testing or advice depending on 
the type of genetic information we generate from your sample. If you experience psychological 
distress or other difficulties, we can also refer you to an appropriate resource for care and/or 
support. 
There may be unforeseeable risks associated with receiving genetic information and the potential 
decisions, actions, or inactions that may be required in response to that information. Please consider 
this carefully and ask any questions that you may have before deciding whether or not to participate 
in this study. 
 
It is important that you consider the risks and uncertainties of this research study that make it 
different from traditional medical testing. 
 
We will make sure that the information that you are given is as accurate as possible to the best of 
our ability. We will use the best standards, practices, and technologies available to researchers. 
However, the technologies available to analyze DNA and our knowledge of how DNA affects health 
are changing rapidly. They are also subject to much uncertainty. Some DNA changes that are 
important to health may be missed, and other DNA changes that are not important may be 
incorrectly identified as if they are important. There are also moral and ethical questions about using 
genetic information on which scientific and medical communities have not yet reached a consensus. 
Therefore, we do NOT guarantee that our test will have the same levels of completeness, accuracy, 
or standardization associated with more traditional medical tests. 
 
Before offering your consent to participate in this research study, please consider all of the risks 
associated with: 
● The return or possible lack of return of results; 
● Whether our interpretation of those results is accurate; 
● How you and/or your family will choose to act upon or not act upon the information or lack 
of information. 
 
Benefits 
You may not benefit directly from taking part in this study. However, your participation may lead to 
new discoveries that help to advance medical research and improve patient care, especially, but not 
only, newborn patient care in the future. Your participation in this study may help to make health 
care and access to health care broader and more representative. 

Page 6 of 14 
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You may find out if there is a change in your child’s DNA that has altered their development. You 
might also find out if this change could affect future biological children. 
A genetic diagnosis may help you connect with other families in the community who face similar 
medical problems. While unlikely, it is possible that a genetic diagnosis may point your doctor to a 
better medical and/or educational treatment. 
You may discover that you or your child are at an increased risk for developing other diseases and 
that information may be of medical benefit. 
None of the above benefits are guaranteed, and it is expected that many participants will not receive 
specific information that is relevant to their health. 
Alternatives 
This is not a treatment study. Your alternative is not to participate in this research study. 
 
HIPAA Research Authorization 
The Health Insurance Portability and Accountability Act of 1996 (HIPAA) provides federal safeguards 
for your protected health information (PHI). State and federal privacy laws also may also require 
your health information to be protected. By signing this form you provide your permission, called 
your “authorization,” for the use and disclosure of PHI. 
 
If you sign this form, the research team working on this study will use and share your health 
information to answer the research questions described in this document, and to make sure that the 
research was done correctly. This includes things learned from the procedures described in this 
consent form. They may also collect other information including your name, address, date of birth, 
medical history, and other information from your medical records from this institution and other 
institutions involved with this research, as well as from your other healthcare providers (which may 
include information about HIV status, drug, alcohol, or sexually transmitted disease treatment, 
genetic test results, or mental health treatment). Those persons who receive your health information 
may not be required by Federal privacy laws (such as the HIPAA Privacy Rule) to protect it and may 
share your information with others without your permission, if permitted by laws governing them. 
 
In most cases, the health information that identifies you can be used or shared by the research team 
only if you give your permission by signing this form. Your health information may be shared with a 
public health authority that is authorized by law to collect or receive such information for the 
purpose of preventing or controlling disease, injury, or disability, and conducting public health 
surveillance, investigations or interventions. 
 
The time period when information can be used or shared ends when all activities related to this study 
are completed. 
 
You do not have to sign this form. If you do not sign this form, you may not participate in the study 
and health information that identifies you will not be shared for research purposes. 

Page 7 of 14 
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Revocation of Research Authorization 
You may withdraw the authorization you have given to use and share your protected health 
information at any time. This means you can tell us to stop using and sharing your protected health 
information. If you withdraw/revoke your authorization: 
• We will stop collecting information about you. 
• You may not withdraw information that we had before you told us to stop. 
o We may already have used it or shared it. 
o We may need it to complete the research. 
o We may need it to search records that are available to the public. 
• Staff may ask your permission to follow-up with you if there is a medical reason to do so. 
To withdraw your authorization, you will be requested to complete a written “Revocation of Research 
Authorization” form located at the end of this document. You may also obtain a copy from your 
study doctor, designated personnel or from the Human Subjects Protections Program Office website 
(https://louisville.edu/research/humansubjects/templates/biomedical-forms). 
Confidentiality 
Information obtained about you for this study will be kept confidential to the extent allowed by law. 
However, research information that identifies you may be shared with people or organizations for 
quality assurance or data analysis, or with those responsible for ensuring compliance with laws and 
regulations related to research. They include: 
● the UAB Institutional Review Board (IRB). An IRB is a group that reviews the study to protect 
the rights and welfare of research participants. 
● The University of Louisville Institutional Review Board, Human Subjects Protection Program 
Office, Privacy Office, others involved in research administration and research and legal 
compliance at the University, and others contracted by the University for ensuring human 
subjects safety or research and legal compliance 
● The local research team 
● People responsible for billing, sending and receiving payments related to your participation in 
the study 
● the NIH National Human Genome Research Institute (NHGRI) 
● the Office for Human Research Protections (OHRP) 
● Office of Civil Rights 
 
The information from the research including your child’s clinical information, family history, and 
genetic variants may be published for scientific purposes; however, your identity will not be given out 
to anyone outside of the clinical team involved with the study. 
 
Your consent form will be placed in your child’s medical record. This may include either a paper 
medical record or electronic medical record (EMR). An EMR is an electronic version of a paper 
medical record of your care within this health system. Your child’s EMR may indicate that you and 
your child are enrolled in this study and provide the name and contact information for the principal 
investigator. 

Page 8 of 14 
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Results of research tests or procedures that have been clinically validated (i.e. Sanger reports) may be 
placed in your child’s medical record. All information within your medical record can be viewed by 
individuals authorized to access the record. 
Information relating to this study, including your name, medical record number, date of birth and 
social security number, may be shared with the billing offices of University of Louisville so costs for 
clinical services can be appropriately paid for by either the study account or by your insurance. 
This research is covered by a Certificate of Confidentiality from the National Institutes of Health. The 
researchers with this Certificate may not disclose or use information, documents, or biospecimens 
that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other 
action, suit, or proceeding, or be used as evidence, for example, if there is a court subpoena, unless 
you have consented for this use. Information, documents, or biospecimens protected by this 
Certificate cannot be disclosed to anyone else who is not connected with the research except, if there 
is a federal, state, or local law that requires disclosure (such as to report child abuse or communicable 
diseases but not for federal, state, or local civil, criminal, administrative, legislative, or other 
proceedings, see below); if you have consented to the disclosure, including for your medical 
treatment; or if it is used for other scientific research, as allowed by federal regulations protecting 
research subjects. 
A federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes it illegal 
for health insurance companies, group health plans, and some employers to discriminate against you 
based on your genetic information. This law generally will protect you in the following ways: 
● Health insurance companies and group health plans may not request your genetic information 
that we get from this research. 
● Health insurance companies and group health plans may not use your genetic information 
when making decisions regarding your eligibility or premiums. 
● Employers with 15 or more employees may not use your genetic information that we get from 
this research when making a decision to hire, promote, or fire you or when setting the terms 
of your employment. 
 
Be aware this federal law does not protect you against genetic discrimination by companies that sell 
life insurance, disability insurance, or long-term care insurance, nor does it protect you against 
genetic discrimination by some employers. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this Web site at any time. 
 
Voluntary Participation and Withdrawal 
Whether or not you take part in this study is your choice. There will be no penalty if you decide not to 
be in the study. If you decide not to be in the study, you will not lose any benefits you are otherwise 
owed. You are free to withdraw from this research study at any time. Your choice to leave the study 
will not affect your relationship with any institution participating in this study. 

Page 9 of 14 
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In the event that you chose to withdraw from the study: 
● No further genetic information from the study will be reported to you. 
● Your blood samples will be destroyed. 
● You will not be contacted to provide new information, additional samples, or 
participate in additional studies related to this project. 
● If the analysis of your DNA has been completed, this information will be retained for the 
study. 
If you would like to withdraw from the study, please contact Dr. Brothers or the study team at 502- 
629-5820. 
Cost of Participation 
There will be no cost to you for taking part in this study. The blood draw, genomic sequencing and 
analysis, and genetic counseling related to this study will be provided to you at no cost during the 
study period. 
After you receive your research results, you may decide with your doctor or your child’s doctor to 
get more testing. The costs of your standard medical care or any services rendered in response to a 
genetic finding identified by this research project will be billed to you and/or your insurance 
company in the usual manner. This type of follow-up medical testing will be considered part of your 
clinical care, and will not be paid for by the research study. 
 
Payment for Participation in Research 
Participation in this study is voluntary and $25 will be provided for each survey completed for a total 
of $125 for your completion of all 5 study-related surveys. Ask the study staff about the method of 
payment that will be used for this study (e.g., check, cash, gift card, direct deposit); payment may 
take up to 4 weeks to process. 
 
Because you will be paid by UAB, to be in this study the University of Louisville may collect your 
name, address, social security number, and keep records of how much you are paid and will need to 
send this information to UAB. You may or may not be sent a Form 1099 by the UAB. This will only 
happen if you are paid $600 or more in one year by the University. This will not include payments 
you may receive as reimbursement for actual expenses based on receipts or actual miles traveled. 
We are required by the Internal Revenue Service to collect this information and you may need to 
report the payment as income on your taxes. 
You can still be in the study even if you don’t want to be paid 
 
Payment for Research-Related Injuries 
UAB, UMMC, HudsonAlpha, Woman’s Hospital, University of Louisville, and NIH/NHGRI/sponsors of 
this research project have not provided for any payment if you are harmed as a result of taking part in 
this study. If such harm occurs, treatment will be provided. However, this treatment will not be 
provided free of charge. 

Page 10 of 14 
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Significant New Findings 
The study doctor or study staff will tell you if new information becomes available that might affect 
your choice to stay in the study. Please note that HudsonAlpha may, but is not required to, reanalyze 
your sample or report any new findings after results have been returned. 
Storage of Specimens for Future Use 
As part of this study, we would like to store some of the blood and DNA specimens collected from 
you and your child for validation of variants (to determine if a variant was inherited from a parent, 
etc.) identified by this project and for future research relevant to rare disease or other genetic 
disorders. The future research may be conducted by the study doctor or by other researchers that 
obtain IRB approval for their research. The specimens will be labeled with a code that only the study 
doctor can link back to you. Results of any future research will not be given to you or your doctor. The 
specimens obtained from you in this research may help in the development of a future commercial 
product. There are no plans to provide financial compensation to you should this occur. You do not 
have to agree to allow your specimens to be stored in order to be part of this study. 
You may at any time withdraw from the study and request that your specimens be removed from 
storage and not be used for future research. If you decide you want your specimens removed, you 
may contact Dr. Bruce Korf at 205-934-9411. Once the request is received, and if your samples have 
not already been used for other research, they will be destroyed. If you do not make such a request, 
your specimens will be stored indefinitely or until used. 
 
Initial next to your choice below: 
 
 
I agree to allow my specimens to be kept in the HudsonAlpha CSL and used for future genetics 
research. 
 
 
I do NOT agree to allow my specimens to be kept and used for future research. 
 
Genomic Data Sharing (GDS) 
We consider the privacy of your information to be of high priority and will take a variety of steps to 
ensure that privacy. However, it is important for researchers to share some of the information that 
they learn from studying human samples. We will never share personally identifiable information, 
like names and addresses, with anyone outside of the research study. However, parts of your 
information may be shared. 
 
Some of your genetic information, limited to a very small subset that will not cause privacy loss risks 
to you, may be published in scientific journals or other unrestricted-access public venues to 
encourage sharing of the knowledge that may be learned by analyzing your DNA and DNA from other 
individuals. This could include information about your child’s symptoms, their age, and any genetic 
findings that we discover. 
 
We may share coded lists of the DNA differences that we identify in public genetic databases. These 
databases gather genetic information from large groups of people and are pooled together such that 
no specific participant can be identified. 

Page 11 of 14 
Version Date: 02/14/2020 
 
There is a very small chance that some commercial value may result from the use of your donated 
samples or genetic information. If that happens, you will not receive a share in any profits. 
Unless you opt out, we may submit your complete genomic data along with some of your coded 
health information to an NIH-designated Data Repository such as dbGAP 
(http://www.ncbi.nlm.nih.gov/gap), AnVIL (https://anvilproject.org/), or another controlled access 
database. Access to dbGAP and AnVIL is only available to qualified researchers at qualified 
institutions who have agreed to abide by certain privacy safeguards, obligating them, both legally 
and ethically, to protect your privacy and to maintain information confidentiality. However, since 
your genetic information is unique to you, there is a small chance that someone could trace your 
information back to you. This risk is very small, but may grow in the future. Some risks and benefits 
are listed below: 
Risks: The risk of sharing your genomic data is that someone could link the information stored 
in the databases back to you. If your information suggests something about your health such 
as increased risk for disease, it could be misused. For example, it could be used to make it 
harder for you to get or keep a job or insurance or be used to discriminate against you or your 
family. There may also be other unknown risks. As stated above (confidentiality section of this 
form), there are federal protections against the misuse of your data (i.e. the Genetic 
Information Nondiscrimination Act, GINA). 
 
Benefits: There is no direct benefit to you from sharing your genomic data with NIH- 
designated repositories, however allowing researchers to use your data may lead to a better 
understanding of how genes affect health which may help other people in the future. 
 
 
Initial next to your choice below: 
 
 
 I agree for my genetic and other relevant study data, such as health information, to be shared 
with NIH-designated repositories such as dbGAP and AnVIL in a coded form for future research 
or analysis 
 
 I do NOT agree for my genetic and other relevant study data, such as health information, to be 
shared with NIH-designated repositories such as dbGAP and AnVIL in a coded form for future 
research or analysis 
 
Contact For Future Research 
As new research opportunities are identified, the researchers may wish to perform additional tests 
on fresh samples or invite eligible participants to enroll in new studies. We would like permission to 
contact you in the future, however this is not a requirement to participate in this study. A separate 
consent form will be obtained if you wish to participate in future research. 

Page 12 of 14 
Version Date: 02/14/2020 
 
Initial next to your choice below: 
 
 
You have permission to contact me about new research opportunities that may interest me. 
 
 
You do NOT have permission to contact me about new research opportunities. 
 
Secondary Findings 
One unanimous decision to receive or not to receive secondary findings must be made by each 
participant family. Because parental samples are only used for confirmation of variation identified in 
the child’s whole genome sequence for this project, only those secondary findings identified in the 
child will be confirmed in the parental samples. Participant families may opt to receive this 
information, if available. If a family chooses to do so, information about an identified secondary 
finding will be included in the child’s medical record. Nothing will be placed in the parent’s medical 
record. 
 
Initial next to your choice below: 
 
 
 
 We (child and parent(s), if enrolled) would like to receive information about secondary 
findings. 
 
 
 
 We (child and parent(s), if enrolled) would NOT like to receive information about secondary 
findings. 
 
Questions 
If you have any questions, concerns, or complaints about the research or a research-related injury 
including available treatments, please contact the study PI Dr. Bruce Korf (UAB) at 205-934-9411 or 
call Dr. Brothers (the site PI) and the UofL study team at 502-629-5820. 
 
If you would prefer to write, you may contact Dr. Brothers or the study team at the University of 
Louisville, 231 East Chestnut Street, Louisville, KY 40202 or email Dr. Brothers at 
kyle.brothers@louisville.edu. 
If you have concerns or complaints about the research or research staff and you do not wish to give 
your name, you may call the toll free number 1-877-852-1167. This is a 24 hour hot line answered by 
people who do not work at the University of Louisville. If you have questions about your rights as a 
research participant, or concerns or complaints about the research, you may also contact the UAB 
Office of the IRB (OIRB) at (205) 934-3789 or toll free at 1-855-860-3789. Regular hours for the OIRB 
are 8:00 a.m. to 5:00 p.m. CT, Monday through Friday. 
Legal Rights 
You are not waiving any of your legal rights by signing this consent form. 

Page 13 of 14 
Version Date: 02/14/2020 
 
Signatures 
Your signature below indicates that you have read (or been read) the information 
provided above and agree to have your child participate in this study. You will receive a copy of this 
signed consent form. 
Your signature below indicates that you have read (or been read) the information provided above 
and agree to participate in this study. You will receive a copy of this signed consent form. 
 
 
Name of Proband Child (printed) 
 
 
Signature of Parent or Legally Authorized Representative 
Date 
 
 
 
 
Mother/Father/Caregiver 
Name of Parent Participant (printed) 
Relationship 
 
 
Signature of Parent Participant 
Date 
 
Mother/Father/Caregiver 
Name of Parent Participant (printed) 
Relationship 
 
 
Signature of Parent Participant 
Date 
 
 
 
 
 
Signature of Person Obtaining Consent 
Date 
 
 
In this research study, one consent form may be used to waive consent for the infant and capture 
informed consent of both parents; however, a separate HIPPA Authorization form will be completed 
for each participant. 
 
Waiver of Assent 
 
The assent of   
 
 
(name of child/minor) was waived because of: 
Age  
 
Maturity  
 
 Psychological state of the child  
 

Page 14 of 14 
Version Date: 02/14/2020 
 
Do not sign this letter unless you are withdrawing from this research. You will be sent confirmation 
that this notice was received. 
REVOCATION OF AUTHORIZATION FOR USE AND DISCLOSURE OF YOUR HEALTH INFORMATION FOR 
RESEARCH 
Return To: 
OR 
 
 
To Whom It May Concern: 
I would like to discontinue my participation in the research study noted above. I understand that 
health information already collected will continue to be used as discussed in the Authorization I 
signed when joining the study. 
Your options are (choose one): 
□ Withdraw from Study & Discontinue Authorization: 
Discontinue my authorization for the future use and disclosure of protected health information. In 
some instances, the research team may need to use your information even after you discontinue 
your authorization, for example, to notify you or government agencies of any health or safety 
concerns that were identified as part of your study participation. 
□ Withdraw from Study, but Continue Authorization: 
Allow the research team to continue collecting information from me and my personal health 
information. This would be done only as needed to support the goals of the study and would not 
be used for purposes other than those already described in the research authorization 
□ Withdraw authorization for use of PHI in optional sub-study. Please describe the change below. 
 
 
 
Printed Name and Signature of Subject 
Date Signed 
 
 
Signature of Subject’s Legal Representative 
Date Signed 
(if subject is unable to sign) 
 
 
Printed Name of Subject’s Legal Representative 
Birthdate of Subject 
 
 
Relationship of Legal Representative to Subject 
 
Subject’s Address 
Subject’s Phone Number 
Optional: 
I am ending my participation in this study because: 
 
PI Address: 231 East Chestnut St. N-97 
Louisville, Kentucky 40202 
PI Phone: 502-629-5820 
Institutional Review Board 
MedCenter One, Suite 200 
501 E. Broadway 
Louisville, KY 40202 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 4: Patient Resources and Learning Topics 

Summary of changes made: 
Based on feedback from Community Engagement Studio 
 
General 
• Made key points briefer and no longer verbatim repeats of detailed text 
• Broke up text with more headers and subheaders 
• Added examples for unexpected result and genetic discrimination sections 
• Added in-text definition of terms 
• Shortened page titles to prevent menu title cut-offs 
New Section 
• Added glossary of common genetics terms 
• Added topic of instructions on how to use Genome Gateway 
• Hyperlinked key words in other topics to glossary 
New Videos 
• SouthSeq overview 
• Genome sequencing 
• Dominant inheritance 
• Recessive inheritance 
• X-linked inheritance 
New Graphics 
• Made “Secondary Findings” graphic more specific to SouthSeq study 
• Increased font for “What to Expect” and “What to Expect Next” graphic text 

Learning assigned at time of consent/enrollment: 

 
Instructions 
Key Points: 
• Genome Gateway is an online tool that helps you participate In the SouthSeq study. 
 
• In Genome Gateway you can build your family health history. 
 
• In Genome Gateway you can explore learning topics. 
 
• In Genome Gateway you can answer important surveys about the study. 
 
• In Genome Gateway you can see and download files, including your child's test results. 
 
• In Genome Gateway you can message with the SouthSeq study team. 
 
 
 
 
Read more... 
Receiving Notifications 
When you there is something new to look at or do in Genome Gateway, you should receive an email and/or text 
message from the system. The message will tell you what kind of new information is available and will have a link 
to click to get to the Genome Gateway website. The picture below shows what an email message from Genome 
Gatewaylooks like. Please keep an eye out for these messages. 
 
You have a message 
lnbox x 
 
SouthSeq noreply@lparticipants.soulhseq.org Id.Imgedu.hudsonalpha.org 
tome• 
 
 
Hello Adam, 
 
Kelly East has sent you a message, view it herel!l!P mcipantssouthseq.O[Q g  
  our dashboard 
 
 
 
.._ Reply 
• 
Forward 

...... 
-· 
Building your family health history 
From your main page in Genome Gateway, click on the family history icon to build your child's family health 
history. By answering a few simple questions about your child's relatives, the system will make your child's family 
tree. You can add details about your child's relatives including their age and any medical conditions they have. This 
information can be very helpful for the study team when the genome sequencing test is done. Watch the following 
video to learn more about how to build your child's family health history in Genome Gateway. 
 
 
Family History 
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Explore learning topics 
From the home page, you can find your assigned learning topics. You will be assigned learning topics at different 
points throughout the SouthSeq study. You can also find learning topics by clicking on the learning tab on the left 
menu bar. When you first enroll, your learning will include topics about the study and genome sequencing testing 
in general. You will also have learning assigned after you receive results from the study. These learning topics are 
available throughout the study. You can log into Genome Gateway at any point during the study to look at learning 
topics. 
 
What to Expect 
key Points: 
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WHAT TO EXPECT 
 
 
 
 
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Answer surveys 
From the home page, you can find your assigned questionnaires. You will be assigned questionnaires at different 
points of the SouthSeq study. You can also find questionnaires by clicking on the questionnaires tab on the left 
menu bar. These questionnaires will help the research team learn more about your experiences with the study. 
We hope that your answers to questionnaires will help families in the future with their genetic testing process and 
experience. 
Current Questionnalre-s 
 
 
 
 
- ­.. 
Previous Quesdonnt1lrcs 
 
 

Download flies 
You can find new files on your home page or click to view previous files from the SouthSeq study. You can also find 
files by clicking on the files tab on the left menu bar. Thisis where you can find your study consent and study 
results files. You can open or download your files by clicking on their name. These files will be kept in Genome 
Gateway throughout the study. 
 
 
 
 
 
 
 
 
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Message the study team 
You can find messages in Genome Gateway from the messages tab in the left menu bar. Members of the study 
team can message you through Genome Gateway, and you can respond to messages in message threads. Thisis 
another way you can ask questions and talk to the study team. To respond to a message, you can click the text bar 
at the bottom of the page to type. You will get a text or email from Genome Gateway when there is a new message 
to read. 
 
 
 
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Link to video: https://vimeo.com/287113637 

Doing this test in a NICU may allow a diagnosis to be made earlier and may help your baby's doctors provide 
better care and treatments. 
 
Study Goal 
The goal of this study is to enroll about 1,500 newborns in the southeastern US. We want to learn if this test is 
helpful in a NICU and to understand the impact this impact has on patients and their families. 
 
Results 
Results from the genome sequencing test will be given back to you and your baby's doctors. It may take 2-4 
months to get the results. 
 
Results may include: 
1. If the test was able to find the reason for your baby's medical problems 
 
2. Genetic changes that may be important for your family's medical care 
 
Learning 
The learning topics here in Genome Gateway will give you more information about the study. 

What to Expect 
Key Points: 
• Your child's blood sample will be used for genome sequencing. 
 
• Results will take 2-4 months. 
 
• You will be asked to complete online questionnaires about your experience at different times. 
 
•  You will be followed by the study staff for up to one year, and the study team maylook at your chlld's 
medical record for up to 8 years. 
 
--- 
WHAT TO EXPECT--- 
j+ 
 
Blood samples and medical 
information are sent to 
HudsonAlpha for testing. 
 
e 
Parents use the online Genome Gateway 
to answer questionnaires and 
learn about the study. 
Newborn's genome is tested 
to look for reasons for 
medical problems. 
 
 
 
 
 
Parents are given results from the 
testing in-person at the NICU. 
Parents answer questionnaires 
after getting results. 
 
Read more... 
Here is a look at what you can expect from your participation in the SouthSeq study. 
 
Genome sequencing testing 
Through the SouthSeq study, a genetic test called genome sequencing will be done for your baby. Genome 
sequencing is a test that looks at all of a person's genetic information called DNA. A blood sample will be collected 
from your baby as well as the biological parents if possible. Genome sequencing will not be done on parent 
samples, rather these samples will be used for follow-up testingdepending on the baby's results. See Genome 
Se uencing for more information on the test. 
(SouthSeq 
 
(southSeq 
0

SouthSeq Steps 
 
1. Blood samples and information about your baby's medical history will be sent to a lab at the HudsonAlpha 
Institute for Biotechnology, in Huntsville, AL for testing. 
2. You will be asked to complete several questionnaires, complete your baby's family history, and read 
educational information inside Genome Gateway. 
3. The lab will look at your baby's DNA sequence and look for anygenetic changes that could be the reason for 
medical problems. 
 
4. Results from the genome sequencing test will take 2-4 months to complete. You will be notified when results 
are ready and a time will be scheduled for you to discuss your results with a healthcare provider in the NICU. 
5. After you receive results from the study you will be asked to complete several additional questionnaires and 
new educational information in Genome Gateway. 
 
 
Questionnaires 
Questionnaires help us learn more about how this type of testing can be used in a NICU and the impact genomic 
results have on patients and their families. We appreciate your participation in this study and willingness to share 
your family's experiences with us. 
 
Genome Gateway for files and communication 
Throughout the study you will have access to Genome Gateway. Within Genome Gateway you will have access to 
files such your study consent form and your baby's results once they they have been discussed with you. You are 
also able to communicate with your SouthSeq study team using the message feature within Genome Gateway. 
 
You will be sent an email and/or text message whenever there is a new questionnaire or new educational topic to 
complete. 
 
You may be contacted by your child's healthcare team or study staff to ask follow-up questions. You will be actively 
involved in the study up to one year. During the year you're involved in the study, researchers will be able to give 
you results, give you questionnaires, and see how medical providers use genome sequencing results in your 
baby's care. 
 
Privacy 
This study will use some of your baby's medical information. Your baby's medical information is kept confidential. 
Names, date of birth, and other information that can be used to identify someone are not shared with anyone 
outside of the research study. Information about this study and genetic results will be in your baby's medical 
record. See the Genetic Discrimination section for more information about genetic privacy. 
 
Withdrawing 
It is important for you to know that you can leave the study and withdraw your consent to participate from the 
SouthSeq study at any time. To withdraw please contact the study coordinator at the NICU where your baby was 
enrolled. If you choose to withdraw from this study, your child's medical care will not be affected. 

If You Have Questions 
Contact Us: 
 
We understand that you may have questions that come up that are not addressed in these learning topics. Use the 
information below as a guide to the best person to contact depending on your specific question or need. 
 
Genome Gateway Messages 
You may have messages through Genome Gateway from members of the study team. You can ask questions on 
message threads. 
 
General health questions 
If you have questions or concerns about your child's health and medical care, please contact your child's 
healthcare providers. 
 
Genome sequencing test questions 
If you have questions about the status of your genome seguenclng test or your results, please contact the study 
coordinator where you were enrolled into the study. 
• University of Alabama at Birmingham Medicine: (205-934-6452) 
 
• Woman's Hospital in Baton Rouge: (225-924-8310) 
 
• University of Mississippi Medical Center: (601-815-3070) 
 
Overall SouthSeq project questions 
If you have questions, concerns, or complaints about the research project, please contact Dr. Bruce Korf at 205- 
934-9411. 
 
If you have questions about your rights as a research participant, you may also contact the UAB Office of the 
Institutional Review Board (IRB) at 205-934-3789. 

Genetics 101 
Key Points: 
 
• A human body is made of cells, and inside our cells Is a complete set of DNA. 
 
• DNA contains genetic "instructions" that ourbodies use and that we canpass to our children. 
 
• A gene Is a section of DNA that tells our bodyhow to do a specific task. 
 
• A person's entire setof DNA is called the genome. 
 
 
 
 
Read more... 
Understanding genetics 
Our understanding of genetics is increasing rapidly. 
We are learning more and more about how changes 
in a person's genes can affect their health and risk of 
developing disease. Newspapers, TV, and the 
Internet often talk about new genes or genetic tests 
related to medical conditions. Genetics can be 
complicated, and it is often difficult to separate fact 
from what is not true. The first step begins with a 
basic understanding of our genes and the human 
genome. Understanding these can help a person make informed decisions when faced with genetic questions. 
 
 
Our bodies are made of cells 
Acell is the basic building block of all living things. Adults have an estimated 10 trillion cells that make up their 
bodies. Inside a cell there is a command center, called the nucleus, that contains the cell's genetic information. 
This genetic information is in the form of DNA. 
 
Cells have DNA 
DNA (deoxyribonucleic acid) contains the genetic instructions that pass information from onegeneration to the 
next. DNA is found in long strands called chromosomes and is very tightly wound to fit inside the nucleus of a cell. 
DNA is made up of four building blocks: Adenine, Thymine, Cytosine, and Guanine, abbreviated A,T,C, and G. 
 
The term genome refers to all of the genetic information present in a cell. There are nearly 3 billion DNA letters in 
a human's genome. 
 
Genes are DNA instructions 
A gene is a specific stretch of DNA that give the cells instructions. These instructions are like a recipe or a blueprint 
for the body. Often, but not always, these instructions tell the cellhow to put together a certain i;iroteln. For 
example, the human genome includes an insulin gene that tells a cell how to produce insulin - a protein that is 
important for digesting sugar. Some genes help decide whether a person is brown or blue-eyed, tall or short. 
Other genes decide the chance that a person will develop a wide variety of diseases. 
 
 
Genes in the human genome 
The human genome contains about 22,000 genes, which makes up only a small part of the total DNA sequence 
(about 2%). The rest of the DNA is made up of sections that control how genes work and sections that are not yet 
well understood. 

 
 
Link to video: https://vimeo.com/287114652 

Read more... 
Genome sequencing 
Genome seguenclng is a test that reads all of our DNA also called a genome. Every person's DNA is made up of 
four letters (A, T, C, G). We all have about 6 billion of these letters - 3 billion that were inherited or passed down 
from each parent. Your baby's genome contains a lot of information! 
 
How the test works 
Genome sequencing is usually done using a blood sample. DNA is taken from blood cells and put into a machine 
that reads the DNA letter sequence (A, T, C,G). The test looks at the order of DNA letters and compares it to a 
standard human genome sequence. Then the lab looks for chances or differences in your baby's DNA. This is like 
spell-check looking for spelling mistakes in a book. 
 
How DNA changes affect health 
Having differences or changes in DNA is not necessarily a bad thing. In fact, everyone has millions of DNA changes. 
Most DNA changes do not affect health. However, sometimes a DNA change can lead to disease. 
 
DNA changes found by this test might be causing current medical problems or cause medical problems that may 
happen in the future. The test may help doctors make a diagnosis that would not be possible using other tests. 
The information can sometimes help doctors and patients make a better decision about treatment. 
 
Genome sequencing finds rare DNA changes 
Genome sequencing is very powerful but not perfect. We are not able to find and understand all the changes in 
DNA. Genome sequencing is best at finding very rare changes and rare medical problems. Genome sequencing is 
not good at finding genetic changes that cause common medical problems like Type 2 diabetes or high blood 
pressure. 

Glossary of Terms 
 
Here is a list of some of the genetic terms and definitions used in the learning sections. 
Some of these words may be new to you. Some of these words you might already know, but they may have a 
different meaning in genetics. 
 
• Benign: harmless, does not cause disease 
 
• Carrier:having one genetic change in a gene where two changes are needed to cause a disease 
 
• Cell: building blocks of life found in every part of the body 
 
• Chromosome: structures that hold long strands of DNA together inside the cells 
 
• dbGAP: research database (runby theNational Institutes of Health) with genome sequencing and symptom 
information 
• De-novo Inheritance: a genetic change that is newin a person and not inherited from parents 
 
• DNA: genetic information made of the letters A, T, C, and G 
 
• Dominant inheritance: when one genetic change in a gene causes someone to have a disease 
 
• Gene: a piece of DNA that hasspecific instructions for the body to grow and work, humans have more than 
20,000 genes 
• Genetic counselor: a health professional with special training in genetics and counseling who helps people 
understand genetics and how genetic changes can impact their health 
 
• Genetic discrimination: being treated differently or unfairly based on your genetic information 
 
• Genetic testing: testing that looks for differences in someone's DNA 
 
• Genome: all of a person'sgenetic information, a person's entire sequence of DNA 
 
• Genome sequencing: a test that reads through all of a person's DNA to look for differences 
 
• GINA (Genetic Information Nondiscrimination Act): federal law that prevents health insurance and 
employers from making decisions based on genetic information 
• Maternal: relatives or information from mom's side of the family 
 
• Nucleus: special area of a cell that stores DNA 
 
• Paternal:relatives or information from dad's side of the family 
 
• Pathogenic: causes a disease or disorder 
 
• Primary result: a result related to the reason for testing (current or past symptoms) 
 
• Protein: gene products that help the body function 
 
• Recessive Inheritance: when two genetic changes in a gene are needed for someone to havea condition 
 
• Secondary result: result not related to the reason for testing (future disease risks) 
 
• Sex chromosomes: the X and Ychromosomes that help determine if someone is born male or female 
 
• Variant of uncertain significance (VUS): genetic change that is not understood enough to be called 
pathogenic or benign 
• X-llnked Inheritance: genetic changes passed down on the X chromosome 
 
• X-inactlvation: process in women where one of the X chromosomes is 'turned off' in every cell of the body 

Types of Results 
Key Points: 
• Results related to why the genetic test was done are primary results. 
 
■ There are 3 primary results: positive, negative, and uncertain. 
 
■  A negative result means nothing was found that's thought to be the cause of your child's medical 
problems. 
• An uncertain result might be the cause of your child's medical problems, but the lab is not sure. 
 
• A positive result is thought to be the cause of your child's medical problems. 
 
 
 
 
Read more... 
 
 
Primary results 
Genome se!juenclng_results that have to do with 
the reason the testing has been done are 
called grlman, results. Genome sequencing looks 
at all of a person's DNA. This test can 
find genetic changes or differences in DNA that can 
cause medical problems. In this study, results that 
explain why your child is having medical problems in 
Negative 
 
the NICU would be primary findings. There are three possible types of primary results you may receive: positive, 
negative, or uncertain. 
 
Negative results 
A negative result means that the lab did not find any genetic changes thought to be the cause of your baby's 
symptoms. A negative test result does not mean that your baby's symptoms are not due to a genetic change. It is 
possible that your baby has a genetic change that is not yet well understood or able to be found. In some cases, 
negative results can be looked at again in the future and a diagnosis may be possible at that time. 
 
Uncertain results 
An uncertain result means that the lab found a genetic change that is not currently able to be understood. This 
genetic change may be the cause for your baby's symptoms but there is not enough proof to be certain. This 
genetic change may also not be the cause of symptoms and just part of typical DNA differences between people. 
Your baby's healthcare provider should not treat an uncertain result as a diagnosis, and should not make medical 
decisions based on this kind of result alone. Over time, many of these uncertain results will be better understood 
and changed to either a positive or negative result. 
 
Positive results 
A positive result means that the lab found a genetic change that is believed to be the cause for your baby's 
medical problems. A positive result can lead to a diagnosis that has clear treatment and support resources. In 
other cases, a baby may be diagnosed with a new or less understood condition. 

Unexpected  Results 
Key Points: 
• Geneticchanges might be found that aren't causing your child's medical problems. These are called 
secondary results. 
• Secondary results might change a person's medical care. 
 
• You will begiven a choice to learn about any secondary results that are found. 
 
• SouthSeq will not provide information about paternity or other family relationships. 
 
 
Types of Secondary Results in SouthSeq 
 
c2 
For example: 
Changes in the MSH6 gene 
lead to a higher chance of 
colon and other cancers 
For example: 
Changes in the LMNA gene 
lead to a higher chance of 
heart problem called 
cardiomyopathy 
For example: 
Changes in the RYR1 gene 
lead to a higher chance of 
bad reaction when exposed 
to some anesthesia medicines 
 
Read more.... 
Secondary results 
Genome se!juenclng_is a test that looks at all of a person's genetic information. During genome sequencing, the 
lab might find a genetic change that is not related to your baby's medical problems, but may still impact the health 
of your child and your family. These types of results are called secondary results. Secondary results returned in 
SouthSeq are genetic changes that put a person at an increased risk of future disease. You can choose whether or 
not you would like to receive secondary results. 

This kind of result may explain a known family history of a disease. In other cases, a secondary result may increase 
risk for a disease that is not in the family history. It's important to know that SouthSeq secondary results do not 
include every genetic future disease risk. 
 
Knowing about secondary results can help lower future disease risk 
If you know about an increased disease risk from a secondary result, there may be steps that can be taken to 
lower the risk for the disease. For example, finding an increased risk for cancer could lead to more cancer 
screening. 
 
The SouthSeq study is only returning secondary results that are treatable or have ways to lower disease 
risk. 
 
Example secondary result 
A SouthSeq secondary result may find a genetic change in a baby that increases the risk for breast cancer. This 
increased risk would be important when the child is an adult. Genetic testing for the child's parents could tell if a 
parent also has the genetic change that increases risk for breast cancer. If a parent has the genetic change, they 
could talk to their doctors about their risk and possibly start breast cancer screenings early. 
 
Family relationships 
In some cases, genome sequencing may find unexpected information about family relationships. For example, 
genetic information may reveal that a child is not biologically related to his or her father or that the parents of a 
child are related to each other. This type of unexpected information will not be reported as part of the 
SouthSeq study. 

.
Implications of Results 
Key Points: 
• The most common result in SouthSeq will be a negative result. 
 
A negative result does not rule out a genetic cause for your baby's medical problems. 
 
• A variant of unknown significance (VUS) result means a genetic change has been found, but we need 
more Information before we can be certain It Is the cause of your baby's medical problems. 
• A positive result means a genetic change has been found that explains the reason for your baby's 
medical problems. 
• In many cases, results do not change your baby'smedical care. 
 
 
 
 
Read more.... 
Negative results 
A negative result is the most common result. This means thatgenome Se!Juenclng looked at all of your 
baby's genetic information but did not finda reason for your baby's medical problems. This does not mean that 
your baby's symptoms are not genetic. There is no perfect test that can find and understand all genetic changes. 
Your baby's doctor may choose to do other types of tests to continue looking for a reason for symptoms. In the 
future, your doctor may also ask that scientists re-read your child's genome sequence. As scientific knowledge 
grows, the test results may be better understood and a diagnosis may be made in the future ------------- 
Variant of uncertain significance results 
Sometimes, a genetic change is found that might be 
the cause of your baby's symptoms. This is called 
a variant of uncertain signlflcance CV:US). More 
information is needed to find out if the change is 
actually the cause of the symptoms or a harmless 
genetic change. Because it is uncertain, this type of 
result should NOT be used to help doctors make 
decisions about medicines or other care for your 
baby. 
Understanding about the disorder 
Useful Information for furure generations 
Potential Insight for treatment 
 
Connections with others with a 
similar diagnosis 
 
Positive results 
In some cases, genome sequencing will find agenetic change that explains the reason for your baby's symptoms 
and gives your family a diagnosis. This means that doctors can stop looking for why your baby has medical 
problems. Sometimes, it also allows family members to learn the chance that someone else in the family could 
have the same symptoms. 
 
What happens if we find a diagnosis? 
Sometimes, getting a genetic diagnosis for your baby can help their doctors better care for them. For example, it 
may tell doctors they should think about using a certain medicine or therapy to treat your baby's symptoms. The 
result may also help doctors decide to stop usingmedicines or therapies that are not working, or inform them 
about treatments that are unlikely to work. Some results may even tell doctors that they should be on the lookout 
for other problems your baby does not currently have. This hopefully keeps more problems from happening later. 
 
In manycases gettinga genetic diagnosis does not change how doctors treat a baby's symptoms. It is possible to 
receive a diagnosis for which there are no approved medications or therapies. However, families can sometimes 
use the result to connect with other families who have children with a similar diagnosis. This can help the families 
feel supported in caring for their child. It can also lead to the chance to be a part of more research, which may at 
some point help doctors learn how to better care for children with the same diagnosis. 

 
Family Impact 
Key Points: 
• It is important to think about what findings from SouthSeq could mean for your family. 
 
• A primary result may provide other family members with a diagnosis. 
 
• A primary result may tell you about the chance other children will have similar problems. 
 
• A secondary result can give future disease risk information to close relatives. 
 
Read more.... 
Family members share DNA 
The impact that genetic test results may have on family members is important to think about with genome 
sequencing. Your baby's genome sequencing will look at all of their genetic information called DNA. Genome 
sequencing is different from most other medical tests. It can give health information about both the patient and 
their family members related by blood. This is because people share their DNA with their family. 
 
Primary result 
Finding a diagnosis for one person may provide a diagnosis for other family members who have similar medical 
problems. Finding a genetic cause for your baby's medical problems may also tell you about the chance for future 
children to have the same condition. 
 
Secondary result 
Secondary results can have important family impacts as well. For example, finding a strong genetic risk factor for 
certain types of cancer in a person means that some of their close relatives likely share the genetic change and 
also have an increased cancer risk. Learning some of these results can be emotionally charged for patients. This is 
especially true if the results impact both the health of the person being tested, as well as the health of their 
siblings, parents, and other family members. 

Data Sharing 
Key Points: 
• You can choose how much information you want to share. Your choices have no impact on your results 
or medical care. 
• The consent form andresults from this study will bein your child's medical record. 
 
•  Some of your child's genetic and medical information (but not name, address or other identifying 
information) will be shared with public genetic databases and published in scientific journals. 
• You can share your child's fullgenome sequence with a private database for scientists called dbGAP. 
 
•  You can allow your child's genome sequence data and left over blood sample to be used in future 
research. 
 
 
 
 
Read more.... 
Information sharing in the study 
As part of this research study, some of your private information may be shared with different people and 
databases. Some of these are not required for you to take part in the study, and you can choose if you want to 
share you child's information. 

Required information sharing 
In medical records 
Everyone who agrees to take part in this research study allows their signed consent form to be put into their 
child's medical record. This means that everyone who can see your child's medical chart will know your family 
agreed to take part in this study. This may include healthcare providers, as well as school systems, insurance 
companies, and anyone else that has access to your child's chart. Results you receive from the research study will 
also be put into their medical chart. 
 
Databases andJournals 
The information from genome seguenclng may also be shared with others outside of this research study. 
Everyone who agrees to take part in this research study allows small parts of their unique genetic sequence to be 
shared to public databases and published in scientific journals. Along with these parts of genetic code, details such 
as your child's age and a list of their symptoms may also be shared. This is to help other doctors and researchers 
learn what this study finds out about genetic changes and how they play a role in illness. These small amounts of 
genetic information cannot be used to identify someone, so no one outside of the research study looking at these 
databases or journals will know that it was your family. 
 
With the laboratory 
In addition, everyone who agrees to take part in this research study allows their blood sample and the genetic 
information contained in their blood sample to be stored at the laboratory. These samples are used to help 
researchers better understand any results that come from this test. An example of this is using the genetic 
information stored at the laboratory to see if a genetic change in a child's blood is also present in their parent's 
blood. 
 
 
Optional information sharing 
Private database (dbGaP) 
There are two more places where samples or genetic information can be shared, but neither of these are required 
in order to take part in this study. The first is a private database called dbGaP. If you agree to have information 
shared to dbGaP, your child's complete genome sequence and some information about their medical problems 
will be included. No names or dates of birth are included, and this is not a public database. The only people that 
can use this database are researchers who have applied for access and agreed to keep it private. A complete 
genome sequence is unique to a person just like a fingerprint, so there is a small chance this could someday be 
used to identify your child. If you are not comfortable with this, you can say "no" to dbGaP and still take part in the 
research study. 
 
Additional research in the lab 
The second place where your sample or information may be used is in the laboratory where the testing is done. As 
mentioned above, you are required to have your sample kept there to better understand the results of this test. 
However, researchers are also interested in using these blood samples to perform other types of genetic research 
on human disease. If you are not comfortable with your or your child's sample being used for any other research 
outside of this specific study, you can say "no" to sample storage and still take part in the research study. 

Genetic Discrimination 
Key Points: 
• Some people are worried about how their genetic information could make it harder to get a job, 
insurance or other service. 
• The Genetic Information Nondiscrimination Act (GINA) is a law preventing health insurances or jobs 
from using genetic information to make decisions. 
 
•  GINA does apply to members of the US military, small businesses, or life, disability, or long-term 
insurances. 
 
 
 
Read more... 
 
Could someone use my or my child's genetic 
Information against them? 
People who are thinking about genome 
seguenclng_may be worried about genetic 
discrimination, or how the genetic test results 
might be used against them in the future. You may 
be worried someone could use genetic information 
to make employment, insurance, or other services 
harder or impossible to get. Genetic information in 
this case means genetic test results, family health 
history, or the fact that a person has seen a genetics 
doctor or been a part of genetic research. 
 
 
 
 
 
 
+ Health Insurance 
.._ 
Companies with more 
Ulitl than 15 employees 
 
 
 
 
 
 
US military or federal 
\"8) goverment employees 
 
.._ 
Companies with fewer 
lllil than 15 employees 
 
Life, disability and 
long-term care insurance 
 
Federal law to prevent genetic discrimination 
In 2008, the Genetic Information Nondiscrimination Act (GINA) was signed into law to reduce genetic 
discrimination. GINA makes it illegal for health insurance companies to decide if someone can have coverage or 
how much they pay for coverage based on genetic information. GINA also prevents insurance companies from 
requiring patients to have genetic testing or asking for the results. This act also keeps many companies from using 
genetic information against an employee to make hiring, firing, or promotion decisions. 
 
What is not covered by the federal law 
GINA does not apply in all cases. For example, companies with fewer than 15 employees do not have to follow 
GINA. GINA also does not apply to the US military or to federal government employees (however, these groups 
often have separate policies in place). Also, life, disability, and long-term care insurance policies are not protected 
by GINA. These companies could still use genetic information to make decisions about coverage. 

For example: 
The results of genome sequencing might show you or your child have an increased risk for cancer. A long-term 
care insurance company might ask about this result and make your coverage cost more because they think there's 
a higher chance you'll have to use the insurance. However, your job couldn't ask you about this result or fire you if 
they know you have an genetic test results that shows an increased risk for cancer. 
 
Things to think about 
You may want to think about possible results or who is able to see genome sequencing results. You can decide if 
you want secondary results that can tell about future disease risk. See Possible UnexP-ected Results for more 
information. You can decide where you want your child's information shared. See Data Access and Storagg for 
more information. 
 
Should I get life, long-term care, or disability Insurance? 
A person thinking about genetic testing may want to apply for life, long-term care, and disability insurance policies 
before genetic testing in case the results show an increased disease risk. In some cases, a genetic test result could 
actually show a person does not have a high chance to have the same disease that is in their family. In this case, 
the genetic test result could help the person applying for these insurance policies. 
 
More questions? 
If you have additional questions or concerns about the possibility of genetic discrimination, we encourage you to 
ask your healthcare provider or visit www.ginahelP-.org. 

Learning assigned at time of result return: 

 
Link to video: https://vimeo.com/287113637 (same as above in overview section) 

What to Expect Next 
Key Points: 
• You will be notified when your results are ready and a results appointment will be scheduled. 
 
• New questionnaires and learning articles will be available to you after your results have been returned. 
 
• You wlllbe actively enrolled In the trial for up to one year. 
 
• We will continue to review your records for up to 8 years and update you with any new information If 
you give permission to be re-contacted. 
 
WHAT TO EXPECT 
 
 
 
 
Blood samples andmedical 
information are sent to 
HudsonAlpha for testing. 
Parents use theonline Genome Gateway 
to answer questionnaires and 
learn about the study. 
Newborn·s genome is tested 
to look for reasons for 
medical problems. 
 
 
 
 
 
 
 
 
 
Parents are given results fromthe 
testing in-person at the NICU. 
Parents answer questionnaires 
after getting results. 
 
 
Read more... 
Next steps to receive study results 
By taking part in SouthSeq, a genetic test called genome seguenclng was done for your baby. When results are 
ready, you will be notified and a time will be scheduled for you to discuss the results with a healthcare provider in 
the NICU. A healthcare provider will go over whether any genetic changes were found that are thought to be the 
cause of your baby's symptoms. The provider will also discuss any medical recommendations based on the test 
result and answer any questions that youmay have. You will be given a copy of the test results as well. 
 
Questionnaires 
When you first enrolled in SouthSeq you were asked to fill outseveral online questionnaires. There are additional 
questionnaires we will ask you to fill out now that results are ready and again in several months. Questionnaires 
help us learn more about how to return genome sequencing results. This may be helpful to other families in the 
future. These questionnaires will be filled out online in Genome Gateway. You will be sent an email and/or text 
message whenever there is a new survey to complete. 
 
(SouthSeq 

 
 
 
Questionnaires will be assigned: 
 
 
• At return of results appointment 
 
• 1 month after results 
 
• 4 months after results 
 
• 4 and a half months after results 
 
 
Learning topics and files will be available in Genome Gateway 
Educational topics, like this one, will continue to be available to you in Genome Gateway until the study closes. We 
encourage you to come back and review this information in the future as needed. You will also continue to have 
access to the shared files (including your consent form and test results) and messaging features within Genome 
Gateway. 
 
Future contact 
You may also be contacted by your child's healthcare team or study staff to answer follow-up questions. You will 
be actively involved in the study for up to one year. It is possible that new information will be discovered about 
your child's genome sequence, even after you have received results from the SouthSeq study. If you have given 
permission to be re-contacted, your child's healthcare team or study staff may contact you with updated 
information about your child's genetic test result. 
 
The study team will continue to look at information in your child's medical record for up to eight years. This is to 
understand the impact of genome sequencing on your child's medical care. After eight years, the data will be kept 
for further research but personal identifiers like name and date of birth will be removed. 
 
Withdrawing 
It is important for you to know that you can leave the study and withdraw your consent to participate from the 
SouthSeq study at any time. To withdraw, please contact the study coordinator at the NICU location where your 
baby was enrolled. If you choose to withdraw from this study, your child's medical care will not be affected. 

Positive Result 
Key Points: 
A positive primary result is agenetic change that likely caused your child's medical problem. 
Many genetic conditions do not have a cure or specific treatment. 
• A positive result may impact your or your child's future family planning. 
 
• There may be support groups or specific organizations for your child's genetic condition. 
 
 
 
 
Read more... 
Primary results 
Primary:results are those related to your newborn's 
medical problems and the reason genome 
se!Juenclng testing was done. 
 
Positive result 
A positive primary result from a genome sequencing 
test means that a genetic change was found that is 
likely the cause of your newborn's symptoms. 
 
How are positive results used? 
A positive primary result may lead to changes in 
medical care. This information may help doctors 
better care for your child. However, many genetic 
conditions do not have specific treatments or cures. 
Sometimes having a genetic diagnosis can provide a 
better picture of what the condition might be like in 
the future. Keep in mind that it is not possible to 
know the exact symptoms that will occur and how 
severe they will be. 
 
Family impacts 
Receiving a positive result could have an impact on your or your family's future family planning. Some genetic 
changes are new in a one person and not found in other relatives. Some genetic changes are inherited and 
passed down through a family. Knowing whether the genetic change found in your child was new or passed down 
can help your healthcare provider give you a more specific estimate of the chance that other family members, 
such as future children, may have the same condition or symptoms. 
 
Result letter 
When you discuss your child's results from the SouthSeq study with the healthcare provider you will also receive a 
copy of the test results and a letter explaining the results in detail. If you receive a positive result, the healthcare 
provider will go over the specific genetic change that was found and what it means for your child's medical care 
and your family. 
 
Finding support 
For some families, receiving a positive result allows them to connect with specific support groups, resources 
and/or research studies specific for the genetic condition that their child has. Your result report will include 
information about currently available resources specific to your child's positive result. In addition, the following 
resources for the larger, rare disease community may also be of interest to you: 
The National Organization for Rare Disorders (NORD) 
 
Global Genes: Allies in Rare Disease 
 
Alabama Rare 
 
Mississipgi Rare Action Network 
Positive 
 

Uncertain Result 
Key Points: 
• An uncertain primary result means we found a genetic change that might be the cause of your child's 
medical problem. 
• There Is not enough Information about the genetic change. There might be more information In the 
future. 
 
• You may be contacted by your healthcare provider or SouthSeq staff for result updates. 
 
 
 
 
Read more... 
Primary results 
Primaryresults are those related to your child's 
medical problems and the reason the g 
q!!..!mQ.Og_testing was done. 
 
Uncertain result 
An uncertain primary result means the study found 
a_genetlc change that is not well understood. There 
is not enough information available to decide if the 
change is actually the cause of symptoms or a 
harmless genetic change. This kind of result is called 
a variant of uncertain significance (¥U . It is 
important to figure out if this genetic change could 
cause symptoms. We all have millions of genetic 
changes and most of them are harmless. 
 
How are uncertain results used? 
Because it is uncertain, this type of result should not 
be viewed as a definite diagnosis. This result may 
not help doctors make decisions about medical care. 
Doctors might recommend more testing for your 
child or family members to get more information 
about the genetic change. Our hope is that over time more will be learned about the genetic change and experts 
will be able to decide whether it is the cause of symptoms. Our knowledge of genetics and disease is constantly 
improving. 
 
Result Letter 
When you discuss your child's results from the SouthSeq study you will receive a copy of the test results and a 
letter explaining the results in detail. If you receive an uncertain result, the healthcare provider will go over the 
specific genetic change that was found. 
 
What if more information Is found? 
During the SouthSeq study, the testing lab might learn more about the variant of uncertain significance. More 
information can help the lab decide whether it is the likely cause of symptoms. You may be contacted by your 
healthcare provider or study staff with new information about your test result. We encourage people who have an 
uncertain result to stay in touch with their healthcare and SouthSeq study team. They can help you find out if new 
information is available for your child's genetic change. 
Uncertain 
 

Negative Result 
Key Points: 
• A negative primary result means we did not find a genetic change that caused your child'smedical 
problem. 
• Your child'smedical problems could still have a genetic cause. 
 
• It Is possible to find a genetic cause with a new genetic test or If the SouthSeq lab looks at your child's 
results again In the future. 
 
 
 
Read more... 
Primary results 
Prima!'.)' results are those that are related to your 
child's medical problems and the reason that 
the genome sequencing testing was done. 
 
 
Negative result 
A negative primary result means no genetic changes 
were found that are thought to have caused your 
child's symptoms. It would be easy to think that this 
means the symptoms are not caused by a genetic 
disorder. However, this is not the case. There are 
many reasons that a person might receive a negative 
result. 
 
Reasons for a Negative Result 
It is possible that your child's symptoms were not 
caused by a single genetic change. Sometimes 
symptoms are caused by many genetic and 
environmental factors. These cases are very difficult 
to diagnose with the types of testing available today. 
 
It is also possible that your child's symptoms were 
caused by a single genetic change that is not able to 
be found with current testing options. There are 
certain types of genetic changes that are very 
difficult to find. We may have found genetic changes 
in your child that are not fully understood. We might understand these changes better in the future with more 
research. 
 
Future Testing 
We will continue to learn more about how genetic changes cause symptoms and human disease. Sometimes, a 
person who had a negative result when they were first tested will later receive a genetic diagnosis. This could 
happen through a new genetic test that might be ordered, or by the laboratory taking another look at your child's 
genome sequence in the future. It is important for you to keep in touch with your child's healthcare providers to 
stay up to dateon testing options and new information. 
Negative 
 

Secondary Results 
Key Points: 
• A secondary result is a geneticchange not related to your newborn's medical problems. 
 
• These results are associated with increased risk for other diseases in the future. 
 
• Stepscan be taken to prevent or reduce disease risk with these results. 
 
• Thisgenetic change was probably inherited from a parent who also has an increased disease risk. 
 
 
 
 
Read more... 
 
A secondary: result or finding is a genetic change that is not related to the reason for testing but may still be 
important to know about. 
 
What kinds of secondary results does SouthSeq look for? 
In addition to searching for a reason for your newborn's medical symptoms, the SouthSeq study also looks for 
changes in a small list of other genes. These genes are related to the possibility of developing other diseases in 
the future, like cancer or heart disease. The study only reports secondary results that have ways to prevent or 
reduce risk of disease. Knowing that someone has a risk to develop a certain disease in the future may mean that 
they need to see a certain kind of doctor or have special tests to check for symptoms. 
 
What does it mean to receive a secondary result? 
Receiving a secondary result means that a genetic change was found that is known to cause an increased risk of a 
particular disease in the future. Sometimes getting a secondary result can explain a person's family history of 
disease. Other times a secondary result is surprising, and found in a person who does not have any family history 
of the disease. Based on the specific result there may be medical changes recommended that lower risk or detect 
disease at an earlier stage. Many of these diseases happen in adulthood. This result will be important to know 
about as your child gets older. 
 
Where did this genetic change come from? 
While it is possible that a secondary result is a brand new genetic change in your child, it is more likely that it was 
passed down from a parent. If the study received blood samples from both parents' samples, we may be able to 
tell you which side of the family the secondary result came from. Knowing which side of the family the result came 
from can help parents know their disease risk. It is important to talk with your child's genetics team or with your 
own doctor about this finding and whether you and your relatives may need genetic testing as well. 

Sharing Your Results 
Key Points: 
•  Your child's genetic results will be included in their medical record, and small parts of their genome 
sequence will be shared on public databases. 
• You may have decided to share your child's genome sequence on a private database. 
 
• You may have decided to let your child's sample be used for future research. 
 
•  You should think carefully about what other medical providers and family members you might llke to 
share your child's results with. 
 
 
 
Read more... 
By participating in SouthSeq, some of your child's private information may be shared with different people and 
databases. Some of these were required for all SouthSeq participants. Other types of sharing were optional. You 
get to decide what types of information you feel comfortable having shared and with whom. 
 
Where was my data automatically shared? 
Everyone who agreed to take part in SouthSeq had their signed consent form put into their child's medical record. 
The genome se9uenclng results you received from the study will also be automatically put into your child's 
medical record. Everyone who agreed to take part in this research study also allowed small, unidentifiable parts of 
their child's unique genetic sequence to be shared to public databases and published in scientific journals. This 
information cannot be used to identify your child or your family. 
 
What choices did I have for more data sharing? 
When you consented to participate in the SouthSeq study you were given the option to share your 
child's genetic information with two other places. The first is a private database called dbGaP to which only 
researchers have access. The second is the laboratory where the genetic testing was done. If you forgot what 
choices you made for data sharing, they are marked on your consent form in the files section of Genome Gateway. 
For more information about the places that your child's data may be shared, review the section on Data Access. 
 
Who should I share my study results with? 
You might want to share your child's SouthSeq study results with other people. As you think about who else might 
need or want to see your child's results, it is important to remember that their genetic test results are private 
health information. Parents can choose how to use and share their child's results. There may be benefit to your 
child, yourself and others in knowing this information. There could also be risks and implications in having your 
child's information shared with others. For more information about these risks and implications, see the learning 
on Genetic Discrimination. 

Sharing with Healthcare Providers 
Participants may choose to share their child's results with other healthcare providers besides the study physician. 
The results you receive may impact multiple aspects of your child's medical care. It may be helpful for providers in 
multiple specialties to see the test results. 
 
Sharing with Family Members 
Results from agenome sequencing test may have implications for you and your family members. In some cases, a 
genetic test result may explain medical symptoms in family members. In other cases, a result mayshow that 
family members are at risk of developing a disease in the future or being a carrier for a genetic condition they 
could pass on to their children. There may be genetic tests that your relatives are interested in having themselves 
based on your family's test results. Your child's healthcare provider will go over any potential impacts on family 
members during your result discussion. 
 

Link to video: https://vimeo.com/293432650 
 
 

Link to video: https://vimeo.com/292783767 
 
 

 
Link to video: https://pod02857.catalyzeapps.com/learning/xlinked-inheritance 

X- linked Genetic Conditions 
A medical condition caused by a change in a gene on the X chromosome is called an X-linked condition. 
 
 
Males have only one X chromosome. This means that a male has only one copy of each of the genes that are on 
the X chromosome. If he has a disease-causing change on his X chromosome, he will have the condition. 
 
Females have two X chromosomes. This means that a female has two copies of each gene on the X chromosome. 
If one of her X chromosomes has a disease-causing change, she will usually not have the condition. This is because 
her other X chromosome contains a working copy of the gene. She would be a carrier for the condition. She can 
pass on the disease-causing change to her children. 
 
How are X-linked Conditions Inherited? 
 
 
When a mother is a carrier for an X-linked condition, four different outcomes are possible: 
1. The child is a boy and is affected and has symptoms of the condition. This happens when a male child inherits 
the genetic change from his mother. Each son has a 1 in 2 chance (50%) of having the condition. 
 
2. The child is a boy and is not offected. This happens when a male child inherits the working gene copy from his 
mother. Each son has a 1 in 2 chance (50%) of not being affected. This child does not have to worry about 
having the condition or passing the condition on to future generations. 
 
3. The child is a girl and is a carrier (but likely not affected). This happens when a female child inherits the genetic 
change from her mother. Each daughter has a 1 in 2 chance (50%) of being a carrier. 
 
4. The child is a girl and is not a carrier (and is not affected). This happens when a female child inherits the working 
copy of the gene from her mother. Each daughter has a 1 in 2 chance (50%) of not being a carrier. This child 
does not have to worry about having the condition or passing the condition on to future generations. 
 
When a father has an X-linked condition, two outcomes are possible: 
1. All daughters will be carriers of that condition. This happens because he has to pass on his X chromosome with 
the genetic change to his daughters. 
2. None of the sons will be affected. This happens because he has to pass on his Y chromosome to his sons. These 
children don't have to worry about passing the condition on. 
 
 
Can girls be affected with an X-linked condition? 
Early in a female's development, one of her two X chromosomes is randomly and permanently "turned off' in each 
of her cells. This is a process called X-lnactlvatlon. X-inactivation is random, so the X chromosome from the 
mother is active in some cells, and the X chromosome from the father is active in other cells. 
 
Most females who are carriers of an X-linked condition do not have any symptoms of the condition. Some females 
do have X-linked condition symptoms. This is a result of uneven, or skewed, X-inactivation. Sometimes, the 
working copy of the gene will be "turned off" in so many cells that the female will have symptoms of the condition. 
The severity of her symptoms depends on the amount of cells where the working copy of the gene remains active. 

New Genetic Change 
Key Points: 
• De novo genetic changes aren't Inherited. They happen for the first time in a child. 
 
•  De novo genetic changes are new in the egg or sperm that made a child. These changes aren't found in 
a parent's blood. 
• A person with a de novo condition can pass their genetic change to their children. 
 
• The chance for a parent to have other children with the same change is less than 1 in 100. 
 
 
 
 
Read more... 
What does de novo mean? 
In some cases, genetic changes are not inherited or passed on from either parent but instead occur for the first 
time in a child. These new genetic changes are called de novo. The word de novo is a Latin word for "new." 
 
How do new genetic changes happen? 
De novo changes happen when an egg or sperm cell has a genetic change that the rest of the parent's cells do not. 
These new genetic changes occur due to random chance as egg and sperm cells are made. If a de novo change 
happens in a gene that causes a dominant disorder, the person will have that disease while the rest of the family 
will not. This is because in a dominant disease, having a single disease-causing change in one copy of the gene is 
enough for someone to have the disease. See Dominant Inheritance for more information. 
 
How does a new genetic change affect risk in family members? 
Even though a person with a de novo change did not inherit the change from a parent with the disease, they do 
have a chance to pass the change on to their children. Each child of a person with a de novo dominant genetic 
condition has a 50%, or 1 in 2, chance to have the same disease as their parent. 
 
For parents of a child with a de novo dominant inherited condition, the chance to have another child with the 
same condition is very low. In rare cases, other eggs or sperm may have the same change as the child with 
symptoms, which would increase the risk for another affected child. We are not able to test all the cells in a 
parent's body to find out if other cells may carry the change. We usually say that the chance for a sibling of a child 
with a de novo dominant condition to be affected is less than 1%, or 1 in 100. This means that if you have more 
children, the chance for them to be born with the same condition as your child is less than 1 in 100. 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 5: Study Flyer 

 
DNA sequencing for newborn nurseries in the South 
Consent Form Summary 
(version 2/18/19) 
 
General 
Information 
You are being asked to take part in a research study. This research study is 
voluntary, meaning you do not have to take part in it. The procedures, risks, 
and benefits are fully described further in the consent form. 
Purpose 
The purpose of the study is to perform a genetic test (whole genome 
sequencing) on babies in the hospital who have symptoms that have not yet 
been diagnosed, but may be genetic. We will also be doing a clinical trial; 
some families will receive results from non-genetics providers and others will 
receive findings from genetic counselors. 
Duration & 
Visits 
If you agree to be in the study, you will be asked to complete 5 surveys and 
have 2 clinic visits (to enroll in the study and to get results). 
Overview of 
Procedures 
There will be one initial visit where we will collect a blood sample from your 
baby and from the child’s biological parents who are willing to give blood 
samples. At this appointment you will also be asked to complete an 
enrollment survey. This initial visit will take approximately 1.5 hours. 
When your results are ready, a nurse will call you to schedule another 
appointment. At that appointment, someone will discuss your results with you 
and you will be asked to complete another survey. We will be audio recording 
the session, but the recordings will not be shared with anyone outside of the 
study team. This result visit will take approximately 1 hour. 
Three other surveys (at 1 month, 4 months, and 4.5 months after you have 
received your results) will be assigned to you online. You will receive an email 
when the survey is available for you to complete. For each survey that you 
complete, we will mail you a $25 check. If you do not have internet at home, 
just tell the nurse and you can use the study iPad in the clinic. 
There is a chance that someone from the research team might call you to ask 
if you would be interested in taking part in an interview. If you are interested, 
they will schedule a time to talk and you will be compensated for your time. 
Risks 
The most likely risks are temporary pain or bruising from the blood draw. 
Completing surveys may cause some individuals to become upset, frustrated 
or tired. Additionally, genetic testing can sometimes provide unexpected 
results which may cause some people to be anxious. If you have any 
questions about the testing performed for this study, please ask the nurse 
coordinator who provided you with this flyer. 
Benefits 
We hope that by sequencing your child’s genome we will be able to determine 
the reason for their symptoms. We also hope to learn more about how to best 
deliver genetic information to families. The knowledge gained from your 
participation will be helpful to patients with rare disease and researchers in 
the future. 
Alternatives 
If you do not want to take part in the study, your alternative is to not 
participate. 

South e 
 
 
 
 
 
 
 
 
 
 
 
 
 
ALABAMA 
KENTUCKY 
LOUISIANA 
MISSISSIPPI 
 
 
 
SouthSeq a NIH-funded':' research study looking at how a 
new kind of genetic test, called whole genome sequencing, 
can be used to try to find the reason for medical problems 
among newborns in a neonatal intensive care unit (NICU). 
1 
2 
3 
4 
 
 
 
 
 
Genes and the Genome 
Genes are the sections of DNA that provides instructions for the 
human body to grow and work properly. A human genome 
contains about 22,000 genes. All of a person's DNA is called 
his or her genome. 
 
Genetic Changes 
All people have changes in their DNA. Genetic changes can 
range from very small to very large. Most genetic changes are 
not related to a medical problem. Some changes are harmful 
and cause disease. These are the types of changes we look 
for in this study. 
5 
 
 
If you have any additional 
questions about this study, please 
contact 205-934-5771. 
hudsonalpha.org/ southseq 
 
*The SouthSeq project (U01HG007301) is supported by the Clinical Sequencing Evidence-Generating Research (CSER) consortium which is funded by 
the National Human Genome Research Institute (NHGRI) with co-funding from the National Institute on Minority Health and Health Disparities (NIMHD) and 
the National Cancer Institute (NCI). More information about CSER can be found at https:/ /cser-consortium.org/. 

South e 
 
 
 
 
 
ALABAMA 
LOUISIANA 
MISSISSIPPI 
 
 
 
SouthSeq is a research study looking at how a new kind 
of genetic test, called whole genome sequencing, can be 
used to try to find the reason for medical problems among 
newborns in a neonatal intensive care unit (NICU). 
1 
2 
3 
4 
 
5 
 
 
Genes and the Genome 
Genes are the sections of DNA that provides instructions for the 
human body to grow and work properly. A human genome 
contains about 22,000 genes. All of a person's DNA is called 
his or her genome. 
 
 
Genetic Changes 
All people have changes in their DNA. Genetic changes can 
range from very small to very large. Most genetic changes are 
not related to a medical problem. Some changes are harmful 
and cause disease. These are the types of changes we look 
for in this study. 
 
 
 
 
 
If you have any additional 
questions about this study, please call 
601-815-5180 or visit 
hudsonalpha.org/southseq. 
 
Principle Investigator: Renate Savich, MD 

South e 
 
 
 
 
 
 
 
 
 
 
 
 
 
ALABAMA 
KENTUCKY LOUISIANA 
MISSISSIPPI 
 
 
 
SouthSeq a NIH-funded':' research study looking at how a 
new kind of genetic test, called whole genome sequencing, 
can be used to try to find the reason for medical problems 
among newborns in a neonatal intensive care unit (NICU). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Genes and the Genome 
Genes are the sections of DNA that provides instructions for the 
human body to grow and work properly. A human genome 
contains about 22,000 genes. All of a person's DNA is called 
his or her genome. 
 
Genetic Changes 
All people have changes in their DNA. Genetic changes can 
range from very small to very large. Most genetic changes are 
not related to a medical problem. Some changes are harmful 
and cause disease. These are the types of changes we look 
for in this study. 
 
 
1 
2 
3 
4 
 
5 
 
 
If you have any additional 
questions about this study, please call 
225-924-8310 or visit 
hudsonalpha.org/southseq. 
 
*The SouthSeq project (U01HG007301) is supported by the Clinical Sequencing Evidence-Generating Research (CSER) consortium which is funded by 
the National Human Genome Research Institute (NHGRI) with co-funding from the National Institute on Minority Health and Health Disparities (NIMHD) and 
the National Cancer Institute (NCI). More information about CSER can be found at https:/ /cser-consortium.org/. 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If you have any additional questions 
about this study, please call 
504-251-2810 or visit 
hudsonalpha.org/southseq. 
 
Site PI: Jessica Patrick-Esteve, MD 

South e 
 
 
 
 
 
 
 
 
 
 
 
 
ALABAMA 
KENTUCKY LOUISIANA 
MISSISSIPPI 
 
 
 
SouthSeq a NIH-funded':' research study looking at how a 
new kind of genetic test, called whole genome sequencing, 
can be used to try to find the reason for medical problems 
among newborns in a neonatal intensive care unit (NICU). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Genes and the Genome 
Genes are the sections of DNA that provides instructions for the 
human body to grow and work properly. A human genome 
contains about 22,000 genes. All of a person's DNA is called 
his or her genome. 
 
Genetic Changes 
All people have changes in their DNA. Genetic changes can 
range from very small to very large. Most genetic changes are 
not related to a medical problem. Some changes are harmful 
and cause disease. These are the types of changes we look 
for in this study. 
 
 
1 
2 
3 
4 
 
5 
 
 
If you have any additional questions 
about this study, please call the 
KCPCRU at 502-629-5820, 
option 1. M-F 8:00-4:30 
 
*The SouthSeq project (U01HG007301) is supported by the Clinical Sequencing Evidence-Generating Research (CSER) consortium which is funded by 
the National Human Genome Research Institute (NHGRI) with co-funding from the National Institute on Minority Health and Health Disparities (NIMHD) and 
the National Cancer Institute (NCI). More information about CSER can be found at https:/ /cser-consortium.org/. 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 6: Provider Training Resources and Fact Sheets 

SouthSeq Provider Live Training 
 
 
Purpose: Equip healthcare providers with the knowledge and skills needed to be able to understand 
genome sequencing results and discuss results with patients and families in a NICU setting. 
 
Background: A major goal of the SouthSeq study is to test a hypothesis that with adequate training 
and support, genome sequencing can be deployed in a NICU setting without the direct involvement 
of genetic specialists. Babies receiving genome sequencing will be randomized to either receive 
results from a genetic specialist (i.e. genetic counselor) or a NICU provider (i.e. neonatologist or 
neonatal nurse practitioner). Results will be discussed with the participant family in-person (ideally) 
or over the phone. Following result disclosure, the participant family will complete questionnaires to 
help the SouthSeq research team understand their experience and outcomes allowing us to test the 
stated hypothesis. 
 
Description: Live training of participating SouthSeq healthcare providers will occur at each study 
site and will in total last approximately 4 hours. The study team will work with each NICU to 
determine the structure of the training to best meet provider’s needs. The training may take place in 
one session or be broken up into multiple sessions over several days. The training will incorporate 
didactic learning, hands-on learning, and small group discussions to achieve the desired learning 
objectives. In addition to live training, materials from the training will be stored in the online Genome 
Gateway education platform for providers to review as needed throughout the study. 
 
Learning Objectives: 
1. Explain the benefits and limitations of genome sequencing and how it compares to other 
types of genetic tests 
2. State the purpose of the SouthSeq study and the hypothesis being tested through result 
disclosure 
3. Identify the role of the non-genetics NICU provider in the SouthSeq study 
4. Demonstrate familiarity and proficiency completing provider tasks in the online Genome 
Gateway platform 
5. Interpret a SouthSeq genome sequencing result letter and report 
6. Develop a plan for disclosing various types of genome sequencing results (positive, 
negative, uncertain) including key points and next steps 
7. Describe common questions among patients receiving genome sequencing results 
8. Attend to psychosocial needs of families surrounding genome sequencing result disclosure 
9. Identify and critique patient support resources relevant to genome sequencing results 

SouthSeq Provider Live Training 
 
 
Tentative Schedule (order and timing to be modified per site): 
15 minutes 
Meet and greet; Get refreshments 
15 minutes 
Introductions; Overview of the SouthSeq study 
Didactic 
Candice Finnila 
(Project Manager) 
15 minutes 
Logistics of return of results in SouthSeq 
Didactic 
Kelly East 
(Genetic Counselor) 
10 minutes 
Q/A 
Kelly East 
15 minutes 
Logistics of the trial 
Didactic 
Liz Rahn 
(Clinical Trial Team) 
45 minutes 
Genome Gateway training 
Hands-on 
Kelly East 
15 minutes 
Whole genome sequencing (WGS) 
Didactic 
Meagan Cochran 
(Genetic Counselor) 
60 minutes 
Returning WGS results 
Didactic; Hands-on; Small group discussion 
Overview: Kelly East 
Role Plays: All GCs 
60 minutes 
Psychosocial skills 
Didactic; Simulation 
Whitley Kelley 
Veronica Greve 
(Genetic Counselors) 
30 minutes 
Wrap up; Q/A 
Kelly East 
 
Description of non-didactic portions of training: 
• 
Genome Gateway Training: providers will use their own device (tablet, laptop) or a provided 
device to log into the Genome Gateway system. They will be led through a series of step by 
step instructions to learn how to 1) review patient information, 2) view files, 3) review 
educational materials, and 4) answer questionnaires. 
• 
Returning WGS results: this session will begin with a brief didactic overview of what 
SouthSeq results look like. Next providers will be given 6 example reports to review. As they 
review these reports they will be asked to answer questions about each result on a written 
table. The goal of this activity is to become familiar with reports and know where to find 
information. Following this activity, attendees will break into smaller groups for a discussion 
facilitated by a genetic counselor. Genetic counselors will have a discussion guide to scaffold 
conversations, highlighting important take home messages and nuances of each example 
result. 
• 
Psychosocial skills: this session will begin with a brief didactic presentation where genetic 
counselors will share their experiences giving genome results to patients and the possible 
range of psychosocial responses. We will also discuss strategies for assessing patient 
understanding and avoiding information overload when presenting genomic information. The 
final activity of the training includes a one-on-one simulation between each participating 
provider and a genetic counselor. The provider will be given the opportunity to practice 
describing an example result to the genetic counselor as well as responding to some typical 
(and not so typical) patient questions. 

1 
 
 
Returning Genome Sequence 
Results in SouthSeq 
Provider Training Session 
 
 
Introductions 
During this training we will discuss: 
An overview of the SouthSeq study 
Logistics of returning SouthSeq results 
Logistics of the trial aspect of SouthSeq 
How to use the online Genome Gateway system 
What whole genome sequencing is, and what it is not 
How to prepare for and give back genome results 
Psychosocial considerations in genetics 
 
Overview of the SouthSeq 
Study 
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2 
 
Primary Goal/Hypothesis 
 
 
 
 
 
 
Specific Aims 
 
 
 
 
 
 
Key Players 
2/1/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Genome Sequencing, Analysis; 
Results Generated at HudsonAlpha 
Genome Sequencing, Analysis; 
Results Generated at HudsonAlpha 
 
 
 
 

3 
 
• confirmed congenital infection 
Enrollment Criteria 
 
•2 or more major congenital anomalies 
•1 major and 2 or more minor anomalies 
•1 major anomaly and an unexplained major medical condition that is not explained by 
prematurity 
•1 major anomaly and a first degree relative with the same major anomaly 
OR, suspicion of a potential underlying genetic condition 
 
Known or strong suspicion for a chromosomal aneuploidy (T13, T18, T21, Monosomy X) 
Disorders with established low genetic yield, e.g., gastroschisis, hydronephrosis, isolated 
congenital heart defects 
confirmed teratogenic exposure 
 
Patient experience 
 
 
 
 
 
 
 
 
 
 
Logistics of return of results 
Return of results is a process by which participant 
families, and the local clinical team, are notified 
about the findings of the genome sequencing test. 
Begins when a result report is ready 
Ends when the results have been documented in 
the medical record and communicated with the 
clinical team 
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4 
 
letters 
From blood sample to result report 
Blood samples sent to HudsonAlpha for sequencing and 
analysis 
Any findings are confirmed in the lab by a second test 
Any findings are discussed at a Variant Review 
Committee (VRC) meeting 
HudsonAlpha genetic counselors translate decisions 
made at the VRC into patient‐friendly result report 
Where you come in… 
Result 
Disclosure 
 
 
 
 
 
 
 
 
Result Ready 
 
 
 
 
Documentation 
and Follow‐Up 
It doesn’t end there… 
The lab at HudsonAlpha may learn new information 
about the results, and issue an updated report 
 
The patient may experience new problems/symptoms 
that could be communicated to the lab 
The patient may have additional questions or concerns 
that need to be addressed 
 
The goal of this training is to equip you, the 
healthcare provider, with information, skills, 
and confidence to give genome sequencing 
results back to patients/families in the 
“experimental arm” of SouthSeq 
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5 
 
Logistics, and some edge cases 
Baby has been discharged prior to results 
Come back to NICU to receive results in 
person 
Baby has passed away prior to results 
Come back to NICU to receive results in 
person 
Family moves or is unwilling to return to 
NICU for results 
Scheduled phone disclosure by same 
provider who would have done in‐person 
disclosure, rest of process stays same 
Family is completely lost to follow‐up 
Letter sent to family notifying of available 
results, results put in medical record 
Safety Nets 
HudsonAlpha GCs here to be a “just‐in‐time” resource 
for you throughout the study 
Specific patient situations that will automatically trigger 
disclosure by control arm (site genetic counselor) 
 
Audio recording of result disclosures (all), monitoring 
and tracking of errors*** 
 
 
Result recording review 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Questions? 
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6 
 
 
 
Logistics of the trial 
Study Population and Timeline 
~1,100 families will be enrolled into the clinical trial 
Start of clinical trial 
 
 
Trial planned to end 6 months into year 4 (Jan. 2021) 
SouthSeq - Workflow 
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7 
 
Hypotheses 
Primary Hypothesis: No clinically relevant difference in the 
parental empowerment between the two arms (trained 
healthcare provider vs. genetic counselor) 
Secondary Hypothesis: Trained health care provider arm 
will be non‐inferior to the genetic counselor arm in terms 
of personal utility and uncertainty X = Y 
Take Away Messages 
The healthcare provider delivering results should not be the 
babies’ current NICU attending MD/NP 
 
Documentation by the healthcare provider to study staff 
about the disclosure session is critical to the fidelity of the 
trial 
 
 
 
 
Genome Gateway 
 
Questionnaires
 
 
 
 
 
 
• A provider account has been created for you. This initiated an email to you with 
a link to finish the setup of your account. 
 
• You will be asked some basic demographic questions and create a unique 
password for your Genome Gateway account 
 
 
2/1/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

8 
 
participants.southseq.org 
• Once initial setup is 
completed, use your email 
address and the unique 
password for your 
Genome Gateway account 
Navigating 
• Use the ‘Home’ page to navigate directly to the 
most relevant areas easily 
Questionnaires 
• Navigate to ‘Questionnaires’ from the homepage 
 
Questionnaires
 
 
 
 
 
 
 
 
 
Log In 
Bookmark this URL! 
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9 
 
Questionnaires 
 
• Complete the Questionnaires assigned to you by selecting 
‘My Surveys’ 
Questionnaires 
• Questions with 
a red Asterix are 
required 
• Please click 
‘Submit’ when 
finished 
• Click on the Questionnaire for the appropriate patient to 
complete it. Note the patient ID is listed with each 
questionnaire 
Learning 
• A predetermined 
set of learning 
articles will be 
assigned to you 
•  You are able to 
see all learning 
topics (including 
participant topics) 
by clicking the “All 
Topics” tab at the 
top of the list. 
• Navigate to ‘Learning’ from the homepage and select 
‘My Learning’ 
Files 
• Files can be 
viewed in the 
internet browser 
or downloaded 
to your 
computer by 
clicking on the 
file name 
• Navigate to ‘Files’ from the homepage and select the 
appropriate patient from the list of users 
2/1/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

10 
 
to your account to read it 
To access all messages, navigate to 'Messages' from the 
homepage 
Messages 
 
Messages 
 
 
 
 
 
Messages 
 
The most recent message 
threads are on the right 
side of the ‘Home’ screen. 
New messages will have a 
blue bar on the left side. 
Click on a message thread 
to open. 
Messages 
 
2/1/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

11 
 
Messages 
To start a new conversation with a SouthSeq user, click '+' 
Messages 
 
 
 
Messages 
 
 
 
 
 
 
Genome Gateway Technical Support 
Technical support can be obtained by contacting 
SouthSeq study staff 
 
 
 
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12 
 
 
 
Whole Genome Sequencing 
In this section we will: 
 
 
 
 
 
WGS sequencing pipeline 
 
 
 
 
WGS…inside the box 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2/1/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

13 
 
Variant filtration 
 
 
 
 
 
 
 
Classifying variants 
 
typically don’t even get reported 
 
treat as innocent until proven guilty 
 
 
WGS vs other genetic tests 
 
 
Helpful in detecting large-scale 
chromosomal changes and 
 
 
Uses Sanger or NextGen 
sequencing to thoroughly 
gains/losses of genetic information 
interrogate a list of genes of interest 
for single nucleotide variation 
Best as a first-line test or when a 
specific diagnosis is highly likely 
Best when the gene list is small and 
 
 
Massively parallel sequencing 
allows investigation of a person’s 
entire** genetic code with “future- 
proof” data output 
(ex: Trisomy 21) 
the diagnostic suspicion 
is high 
Best when the phenotype is 
nonspecific or the gene list is 
large 
Low resolution – a normal result 
does not rule out much 
Limited possibility for reanalysis 
Higher likelihood of VUS/GUS and 
secondary findings 
 
 
WGS vs other genetic tests 
 
 
 
 
 
2/1/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

14 
 
Limitations of WGS 
Technical limitations: 
 
 
 
Analytical limitations: 
 
 
 
Logistical limitations: 
 
 
 
Words of caution 
 
 
 
 
 
 
 
 
 
 
Questions? 
 
Returning Genome 
Sequencing Results 
2/1/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

15 
 
group discussion 
Technical “Sanger” Report about any gene changes found 
ID2 = SouthSeq Participant ID 
First two letters indicate site (BR = Baton Rouge) 
Followed by unique set of numbers 
Final letter indicates which individual in the family the 
report pertains to 
P = proband (affected baby) 
M = mom 
D = dad 
S = sibling (not usually applicable) 
 
In this section we will: 
Review the format and contents of SouthSeq result 
reports 
Discuss how to use result reports to prepare for the 
result disclosure conversation 
Practice preparation for result disclosure using a series 
of example case reports 
 
Contents and structure of SouthSeq result reports 
 
All SouthSeq participants will receive a letter from 
HudsonAlpha summarizing their results. 
 
If a genetic variant is being returned, a technical “Sanger” 
lab report will accompany the letter. 
 
 
 
 
 
 
 
 
 
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16 
 
What you will not find in the result report 
 
 
 
 
 
 
The result report/letter is your guide 
 
Key talking points and take home messages 
Resources to share with participant/family 
Written in patient‐friendly language 
If you have questions… 
Your HudsonAlpha GC: 
[Birmingham: Meagan Cochran; Jackson: Whitley 
Kelley; Baton Rouge: Veronica Greve] 
 
Genome Gateway messaging best and most secure 
communication method (can discuss PHI/clinical details). 
Let’s Practice… 
 
 
 
 
 
 
 
 
2/1/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

17 
 
 
Psychosocial considerations 
in the context of genetics 
 
 
 
Delivering Genomic Results 
Are genomic result disclosures different from other patient 
interactions? How? 
 
 
 
 
 
 
Delivering Genomic Results 
Understanding the familial context of the result makes 
information more meaningful 
Counseling the family, not the result 
Delivering Genomic Results 
Avoid information overload 
 
 
Try to use terminology participants understand 
2/1/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

18 
 
Delivering Genomic Results 
What if participants don’t want to hear part or all of 
results? 
 
 
 
 
Assessing Patient Understanding ‐ Questions 
Questions are helpful to clarify patient meaning and check 
your assumptions 
Avoid over‐questioning and interrogating patients 
Open‐ended questions are helpful for assessment 
Try to avoid close ended questions 
Assessing Patient Understanding ‐ Information 
Start from relevant basics 
After concepts, pause to assess 
 
Look for nonverbal cues 
Emotional reactions may impede information 
understanding 
Assessing Patient Understanding – Emotional 
Reaction 
Anger 
Grief 
Guilt 
Shame 
Relief 
 
 
 
2/1/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

19 
 
• Escape‐avoidance 
Assessing Patient Understanding ‐ Emotional 
Reaction 
Positive coping strategies: 
 
 
 
Negative coping strategies: 
 
 
 
 
Assessing Patient Understanding ‐ Misconceptions 
Participants may have underlying misconceptions about 
genetics and disease 
Numerical risk information may be difficult for participants 
to understand 
Consider whether you are challenging a family’s 
misconception or cultural perspective 
Let’s Practice 
Case assignment 
 
Review the case and list on your result return sheet: 
 
 
Simulation 
15 minutes for case simulations 
Deliver these results as if the genetic counselor is an actual 
participant 
Feel free to use the resources and information identified in 
the previous activities 
2/1/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

20 
 
Role‐play Wrap‐up 
 
 
 
 
 
Case F 
 
 
 
 
 
 
 
 
 
 
Case B 
 
 
Assumption of inheritance 
“If it didn’t come from me, it came from her dad, and 
he’s fine, so my child will be fine too.” 
 
Blame 
“This must be her dad’s fault.” 
Case B 
 
 
Misunderstanding of natural history of condition 
“I know this came from her dad’s side because his mother 
has heart problems.” 
 
Discussion of intellectual disability during neonatal period 
“Will my child be able to live independently as an adult?” 
2/1/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

21 
 
“God will heal my baby.” 
“This is because of the chemicals on the farm I grew up on.” 
caused this.” 
Case C 
 
Misunderstanding of inheritance 
“No one in our family has anything like this. The test must be 
wrong.” 
 
Seeking solutions 
“Is there anyone who can help her? We will try anything.” 
Religious/cultural beliefs + potential denial 
Case E 
 
Guilt 
“This is my fault.” 
“Why are his symptoms so much worse than mine? Did I do 
something to make them worse?” 
Misunderstanding of variable expressivity 
“You’re saying I have this too, but I’m not sick. The test must 
be wrong.” 
Case D 
 
 
Misunderstanding of natural history and purpose of surveillance 
guidelines 
“Will doing the tests you’re talking about cure her?” 
Misunderstanding of inheritance 
“Does this mean he is not/I am not the father?” 
Guilt/blame, misunderstanding of de novo variants 
Case A 
 
 
Misunderstanding of limitations 
“So this isn’t genetic?” 
“Now I can tell my sister this isn’t something her kids can 
get.” 
Guilt, personal narrative 
“I knew nothing was going to come back, because I drank a 
glass of wine when I was 10 weeks pregnant and that’s what 
2/1/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

22 
 
pancreatic cancer risk 
have immediate medical management implications 
immediately after receiving their result? 
Example of Complex Result 
 
Child born with multiple congenital anomalies and hearing loss 
Result: maternally inherited pathogenic PALB2 variant 
PALB2: tumor suppressor; homozygous or compound heterozygous 
variation causes Fanconi anemia 
Heterozygous variation causes increased breast and 
Example of Complex Result 
Primary result with secondary implications 
Unable to identify “second hit” in PALB2 
Uncertain diagnostic result 
Discussing increased adulthood cancer risk for an infant 
Disclosing increased risk of cancer to a parent for whom this should 
Resource‐finding 
 
Take 2‐3 minutes to Google your case’s result (including Google 
images) 
What do you find? 
 
What, if anything, would be helpful for families? 
What, if anything, would you rather families NOT see 
Resource‐finding 
GeneReviews, Genetics Home Reference 
Unique 
 
Simons VIP Connect 
 
Facebook groups 
Parent blogs 
2/1/2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

23 
 
Recap of your role: for each result you disclose 
 
 
2 
 
3 
 
3 
 
 
Wrap Up 
Questions? 
Next Steps 
2/1/2019 
 
 
 
 
 
 
 
 
 
 

Pre-Training Survey 
1. What is your primary role as a healthcare provider? 
 Physician (MD/DO) 
 Nurse practitioner (APRN/MSN/DNP) 
 Physician’s Assistant (PA-C) 
 Genetic counselor 
 Other  
 
2. What is your specialty? (select all that apply) 
 General Internal Medicine 
 Internal Medicine Subspecialty  
 
 General Pediatrics 
 Pediatrics Subspecialty  
 
 Family practice 
 General Med/Peds 
 Med/Peds Subspecialty  
 
 Neurology 
 Ob/Gyn 
 General Surgery 
 Surgery Subspecialty  
 
 Psychiatry 
 Hem/Onc 
 Medical Genetics 
 Other  
 
3. Have you received any of the following formal genetics education (not including college 
or professional degree)? (select all that apply) 
 Genetics residency or fellowship 
 Genetics education course/CME (online or in person) 
 Residency rotation in genetics 
 Graduate degree (in addition to your professional degree) focused on genetics 
 Other 
 I have had no formal genetics training. 
4. How many years have you been in practice (since residency/training ended)? 
 0-5 years 
 6–10 years 
 11–15 years 
 16–20 years 
 21–25 years 
 >25 years 
5. Please pick the category that best describes your race/ethnicity: (select all that apply) 

 American Indian or Alaska Native 
 Asian 
 Black or African American 
 Hispanic or Latino 
 Native Hawaiian or Other Pacific Islander 
 White 
6. Have often, on average, are you involved in ordering genetic testing (karyotype, 
microarray, gene sequencing, exome/genome sequencing) for a patient as part of your 
clinical practice? Pick the answer that best describes your experience. 
 Every day 
 Once per week 
 Once per month 
 Once per year 
 I have never ordered a genetic test 
7. Which of the following types of genetic test results have you ordered for a patient as 
part of your clinical practice? (select all that apply) 
 Karyotype 
 Microarray 
 Single gene test or small panel test (<10 genes) 
 Large gene panel test (>10 genes) 
 Mitochondrial DNA testing 
 Exome sequencing 
 Genome sequencing 
 Other  
 
 I have never ordered a genetic test 
8. How confident do you feel in your ability to read and interpret genetic test results? 
 Not at all confident 
 A little confident 
 Somewhat confident 
 Very confident 
9. Have you ever seen a whole genome sequencing result report for a patient as part of 
your clinical practice? 
 Yes 
 No 
 Unsure 
10. How confident do you feel in your ability to read and interpret a whole genome 
sequencing test result? 
 Not at all confident 
 A little confident 

 Somewhat confident 
 Very confident 
11. How confident do you feel in your ability to explain a whole genome sequencing test 
result to a patient/family? 
 Not at all confident 
 A little confident 
 Somewhat confident 
 Very confident 
12. How confident do you feel in your ability to manage a patient’s care based on a whole 
genome sequencing result? 
 Not at all confident 
 A little confident 
 Somewhat confident 
 Very confident 
13. Which of the following do you feel are significant barriers to the implementation of 
whole genome sequencing in routine NICU clinical care? (select all that apply) 
 Test cost 
 Lack of insurance coverage 
 Limited diagnostic value 
 Possibility of unexpected results 
 Possibility of uncertain results 
 Limited healthcare provider time 
 Lack of healthcare provider knowledge/training 
 Lack of patient understanding 
 Turn around time 
 Other  
 
 There are no barriers 

Post-Training Survey 
1. To what extent do you feel this training has increased your understanding of genomics 
and the role it can play in making a diagnosis? 
 Not at all 
 A little 
 Somewhat 
 Very 
2. To what extent do you feel that this training has equipped you with the knowledge and 
skills needed to implement your role in the SouthSeq study? 
 Not at all 
 A little 
 Somewhat 
 Very 
3. How confident do you feel in your ability to read and interpret a whole genome 
sequencing test result? 
 Not at all confident 
 A little confident 
 Somewhat confident 
 Very confident 
4. How confident do you feel in your ability to explain a whole genome sequencing test 
result to a patient/family? 
 Not at all confident 
 A little confident 
 Somewhat confident 
 Very confident 
5. How confident do you feel in your ability to manage a patient’s care based on a whole 
genome sequencing result? 
 Not at all confident 
 A little confident 
 Somewhat confident 
 Very confident 
6. What aspect of training was most valuable to you?  
 
7. What aspect of training was least valuable to you?  
 
8. Are there any topics that you wished had been covered, or covered more deeply? If so, 
what are they?  
 

9. Do you feel that the format and structure of this training was appropriate for the topics 
(length, inclusion of discussion, hands-on, and simulation)? 
 
 
 
10. How often do you expect to refer to the online version of training materials in the 
future? 
 Not at all 
 Rarely 
 Sometimes 
 Very often 
11. Is there any other feedback you would like to provide about the training?  
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 7: Survey Measures by Time Point 

 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 7.1 
Enrollment Survey 

SouthSeq Baseline/Enrollment Survey 
* indicates required question 
 
1. *Please identify the individual completing this survey. 
 Mother 
 Father 
 Other (please specify):  
 
 
2. *What is your age? 
3. *Do you speak another language besides English? (Check one)* 
 Yes (If marked, complete next 2 questions) 
 No 
• 
How well do you speak English? 
 Native English-speaker 
 Very well 
 Well 
 Not well 
• 
What language do you prefer to speak with your child’s doctors? 
 English 
 Another language (If marked, please select language from the list below) 
 I am equally comfortable discussing my child’s medical care in both English and 
another language 
 
• 
Please tell us which language you prefer to speak with your child’s doctors: 
 Spanish 
 Vietnamese 
 Chinese (Mandarin, Cantonese, or other Chinese language) 
 Tagalog 
 German 
 French 
 Korean 
 Russian 
 Arabic 
 Other (please specify):  
 
 
4. *What category or categories best describe you? Check all that apply. 
 American Indian, Native American, or Alaskan Native 
 Asian 
 Black or African American 
 Native Hawaiian/Pacific Islander 
 White or European American 
 Middle Eastern or North African/Mediterranean 
 Hispanic/Latino(a) 
 Prefer not to answer 

SouthSeq Baseline/Enrollment Survey 
* indicates required question 
 
 Unknown/None of these fully describe me 
 
5. *What category or categories best describe your child? Check all that apply. 
 American Indian, Native American, or Alaska Native 
 Asian 
 Black or African American 
 Native Hawaiian/Pacific Islander 
 White or European American 
 Middle Eastern or North African/Mediterranean 
 Hispanic/Latino(a) 
 Prefer not to answer 
 Unknown/None of these fully describe my child 
 
6. *Are you currently (please select one): 
 Married 
 Living together but not married 
 Separated or Divorced 
 Widowed 
 Never married and currently not living together 
 
 
7. *What is your employment status from this past week? (check all that apply) 
 Working for pay at a job or business 
 With a job or business but not at work 
 Looking for work 
 Working, but not for pay, at a family-owned job or business 
 Not working at a job or business 
 Not looking for work 
 Taking care of house or family 
 Going to school 
 Retired 
 Disabled 
 Other:  
 
 Prefer not to answer 
 Don’t know 
8. *What was your household’s total family income (before taxes) from all sources in the 
last year? (Check one) 
 Less than $10,000 
 $10,000 to $14,999 
 $15,000 to $19,999 
 $20,000 to $24,999 
 $25,000 to $29,999 
 $30,000 to $39,999 
 $40,000 to $49,999 
 $50,000 to $59,999 

SouthSeq Baseline/Enrollment Survey 
* indicates required question 
 
 $60,000 to $69,999 
 $70,000 to $79,999 
 $80,000 to $99,999 
 $100,000 to $119,999 
 $120,000 to $139,999 
 $140,000 or more 
 Prefer not to answer 
9. 
How many people (children and adults) were supported by this income in the last year? 
 
 
 
10. *What is the highest grade or level of school you completed or the highest degree you 
received? (Check one) 
 No schooling completed 
 Elementary school (kindergarten through 5th grade) 
 Middle school (6th, 7th, or 8th grade) 
 Some high school (9th, 10th, or 11th grade) 
 12th grade, no diploma 
 High school graduate (diploma or GED or equivalent) 
 Some post-high school training (college or occupational, technical, or vocational 
training), no degree or certificate 
 Completed occupational, technical, or vocational program, received degree or 
certificate 
 Associate (2-year) college degree 
 Bachelor’s degree (for example: BA, AB, BS) 
 Master’s degree (for example: MA, MS, MEng, MEd, MSW, MBA) 
 Professional degree (for example: MD, DDS, DVM, LLB, JD) 
 Doctoral degree (for example: PhD, EdD) 
 
11. *Are you covered by health insurance or some other kind of health care plan? (Include 
health insurance obtained through employment or purchased directly, as well as 
government programs like Medicare and Medicaid that provide medical care or help pay 
medical bills) (Check one) 
 No 
 Yes 
12. If you answered yes for #11: What kind or kinds of health insurance or health care coverage 
do you have? (Check all that apply) 
 Private health insurance, employment based 
 Private health insurance, directly purchased 
 Government plan, Medicare 
 Government plan, Medicaid 
 Government plan, Military health care 
 Other type of insurance (Please Describe):  
 

SouthSeq Baseline/Enrollment Survey 
* indicates required question 
 
 No coverage of any type. 
 
13. *Is your child covered by health insurance or some other kind of health care plan? 
(Include health insurance obtained through employment or purchased directly as well as 
government programs like Medicare and Medicaid that provide medical care or help pay 
medical bills) (Check one) 
 No 
 Yes 
 
14. If you answered yes for #13: IF YOUR CHILD IS COVERED: What kind or kinds of 
health insurance or health care coverage do they have? (Check all that apply) 
 Private health insurance, employment based 
 Private health insurance, directly purchased 
 Government plan, Medicare 
 Government plan, Medicaid 
 Government plan, Military health care 
 Other type of insurance (Please Describe):  
 
 No coverage of any type. 
 
 
15. *Which of the following currently applies to your child? 
 My child is currently in the hospital 
 My child is now living outside the hospital 
 My child is no longer living (if selected, skip to Question 17) 

16. How good is your child’s health TODAY? 
SouthSeq Baseline/Enrollment Survey 
* indicates required question 
 
 
 
 
 
• We would like know how good or bad your 
child’s health is TODAY. 
• This line is numbered 0 to 100. 
• 100 means the best health you can imagine. 
0 means the worst health you can imagine. 
• Mark an X on the scale to indicate how your 
child’s health is TODAY 
• Now please write the number you marked on 
the scale in the box below 
 
 
 
 
 
 
YOUR CHILD’S HEALTH TODAY=  
 
o N/A 

SouthSeq Baseline/Enrollment Survey 
* indicates required question 
 
17. *Considering your child’s medical condition, please rank the degree to which you 
agree with the following statements: 
 
Strongly 
Disagree 
Disagree 
Somewhat 
Disagree 
Neutral Somewhat 
Agree 
Agree Strongly 
Agree 
I am clear in my own 
mind why my family 
has enrolled in 
SouthSeq. 
I can explain what the 
condition means to 
people in my family 
who may need to 
know. 
I understand the 
impact of the condition 
on my child(ren)/any 
child I may have. 
When I think about the 
condition in my family, 
I get upset. 
I don’t know where to 
go to get the medical 
help I/my family need 
(s). 
I can see that good 
things have come 
from having this 
condition in my family. 
I can control how this 
condition affects my 
family. 
I feel positive about 
the future. 
I am able to cope with 
having this condition 
in my family. 
I don’t know what 
could be gained from 
each of the options 
available to me. 
Having this condition 
in my family makes 
me feel anxious. 
I don’t know if this 
condition could affect 
my other relatives 
(brothers, sisters, 
aunts, uncles, 
cousins). 

SouthSeq Baseline/Enrollment Survey 
* indicates required question 
 
In relation to the 
condition in my family, 
nothing I decide will 
change the future for 
my children/any 
children I might have. 
I understand the 
reasons why my 
child’s doctor referred 
my family to SouthSeq 
I know how to get the 
non-medical help I/my 
family need(s) (e.g. 
educational, financial, 
social support). 
I can explain what the 
condition means to 
people outside my 
family who may need 
to know (e.g. 
teachers, social 
workers). 
I don’t know what I 
can do to change how 
this condition affects 
me/my children. 
I don’t know who else 
in my family might be 
at risk for this 
condition. 
I am hopeful that my 
child(ren) can look 
forward to a rewarding 
family life. 
I am able to make 
plans for the future. 
I feel guilty because I 
(might have) passed 
this condition on to my 
children. 
I am powerless to do 
anything about this 
condition in my family. 
I understand what 
concerns led to my 
referral to SouthSeq 
I can make decisions 
about the condition 
that may change my 
child(ren)’s future/the 

SouthSeq Baseline/Enrollment Survey 
* indicates required question 
 
future of any child(ren) 
I may have. 
 
 
18. For each item, rate yourself on the scale from “Not at all Good (1) to Extremely good (6)” 
 
 
a. How good are you at working with fractions? 
 
Not at all 
good 
Extremely 
Good 
1 
2 
3 
4 
5 
6 
b. How good are you at figuring out how much a shirt will cost if it is 25% off? 
 
Not at all 
good 
Extremely 
Good 
1 
2 
3 
4 
5 
6 
c. How often do you find numerical information to be useful? 
 
Never 
Very often 
1 
2 
3 
4 
5 
6 
 
 
19. *Please mark the following statements as True or False. 
 
True 
False 
It is possible to see a gene with the naked eye. 
Healthy parents can have a child with a hereditary disease. 
The onset of certain diseases is due to genes, environment and 
lifestyle. 
The carrier of a disease gene may be completely healthy. 
All serious diseases are hereditary. 
Genes are inside cells. 
The child of a disease gene carrier is always also a carrier of the 
same disease. 
A gene is a piece of DNA. 
A gene is part of a chromosome. 
All body parts have all of the same genes. 
It has been estimated that a person has about 20,000 genes. 
A person’s race and ethnicity can affect how likely they are to get a 
disease. 
Each of us has variations in our genes that make it more likely that 
we will get certain diseases. 
A “complex disease” is a health condition brought on by many 
genes and lifestyle and environment. 
A single nucleotide polymorphism or “SNiP” is a variation present in 
some individuals that stretches across a large section of DNA. 

SouthSeq Baseline/Enrollment Survey 
* indicates required question 
 
20. Rate how certain you anticipate feeling about the following aspects of your child’s upcoming 
sequence results: 
 
Very 
Uncertain (1) 
2 
3 
4 
Very 
Certain (5) 
What my child’s 
future test results 
may mean for 
his/her health 
What future actions I 
will need to take 
based on my child’s 
test results 
How my child’s 
physician may use 
the future results to 
improve my child’s 
health 
Whether I will be 
worried or 
concerned about my 
child’s future test 
results 
Whether my child’s 
future test results 
will reveal 
something alarming 
Whether my child’s 
future test results 
will disrupt my 
child’s life 
Whether I will be 
able to trust my 
child’s future test 
results 
Whether my child’s 
future test results 
will be accurate 

SouthSeq Baseline/Enrollment Survey 
* indicates required question 
 
21. *Please rank the degree to which you agree with the following statements 
 
 
Always 
Often 
Sometimes Occasionally 
Never 
How often do you have 
someone (like a family 
member, friend, hospital/clinic 
worker, or caregiver) help you 
read medical materials? 
How often do you have 
problems learning about your 
medical condition because of 
difficulty reading written 
information? 
How often do you have a 
problem understanding what 
is told to you about your 
medical condition? 
Not at all 
A little bit 
Somewhat 
Quite a bit 
Extremely 
How confident are you filling 
out forms by yourself? 
 
 
22. *In general, would you say your health is: 
 
Excellent 
Very Good 
Good 
Fair 
Poor 
 
 
 
23. *Here are some questions about the support that is available to you. 
a. About how many close friends and close relatives do you have (people you feel at ease 
with and can talk to about what is on your mind)? 
Write in number of close friends and close relatives: 
 
 
b. People sometimes look to others for companionship, assistance, or other types of 
support. How often is each of the following kinds of support available to YOU if you need 
it? 
 
None of 
the time 
A little of 
the time 
Some of 
the time 
Most of 
the time 
All of the 
time 
Someone to help you if you were 
confined to bed… 
Someone you can count on to listen 
to you when you need to talk… 
Someone to give you good advice 
about a crisis… 
Someone to take you to the doctor if 
you needed it… 

SouthSeq Baseline/Enrollment Survey 
* indicates required question 
 
Someone who shows you love and 
affection… 
Someone to have a good time with… 
Someone to give you information to 
help you understand a situation… 
Someone to confide in or talk to 
about yourself or your problems… 
Someone who hugs you… 
Someone to get together with for 
relaxation… 
Someone to prepare your meals if 
you were unable to do it yourself… 
Someone whose advice you really 
want… 
Someone to do things with to help 
you get your mind off things… 
Someone to help with daily chores if 
you were sick… 
Someone to share your most private 
worries and fears with… 
Someone to turn to for suggestions 
about how to deal with a personal 
problem… 
Someone to do something enjoyable 
with… 
Someone who understands your 
problems… 
Someone to love and make you feel 
wanted… 

 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 7.1A 
Enrollment Survey for Deceased Probands 

SouthSeq Baseline/Enrollment Survey (deceased proband) 
* indicates required question 
 
1. *Please identify the individual completing this survey. 
 Mother 
 Father 
 Other (please specify):  
 
 
2. *What is your age? 
3. *Do you speak another language besides English? (Check one)* 
 Yes (If marked, complete next 2 questions) 
 No 
• 
How well do you speak English? 
 Native English-speaker 
 Very well 
 Well 
 Not well 
• 
What language do you prefer to speak with your child’s doctors? 
 English 
 Another language (If marked, please select language from the list below) 
 I am equally comfortable discussing my child’s medical care in both English and another 
language 
 
• 
Please tell us which language you prefer to speak with your child’s doctors: 
 Spanish 
 Vietnamese 
 Chinese (Mandarin, Cantonese, or other Chinese language) 
 Tagalog 
 German 
 French 
 Korean 
 Russian 
 Arabic 
 Other (please specify):  
 
 
4. *What category or categories best describe you? Check all that apply. 
 American Indian, Native American, or Alaskan Native 
 Asian 
 Black or African American 
 Native Hawaiian/Pacific Islander 
 White or European American 
 Middle Eastern or North African/Mediterranean 
 Hispanic/Latino(a) 
 Prefer not to answer 

SouthSeq Baseline/Enrollment Survey (deceased proband) 
* indicates required question 
 
 Unknown/None of these fully describe me 
 
5. *What category or categories best describe your child? Check all that apply. 
 American Indian, Native American, or Alaska Native 
 Asian 
 Black or African American 
 Native Hawaiian/Pacific Islander 
 White or European American 
 Middle Eastern or North African/Mediterranean 
 Hispanic/Latino(a) 
 Prefer not to answer 
 Unknown/None of these fully describe my child 
 
6. *Are you currently (please select one): 
 Married 
 Living together but not married 
 Separated or Divorced 
 Widowed 
 Never married and currently not living together 
 
 
7. *What is your employment status from this past week? (check all that apply) 
 Working for pay at a job or business 
 With a job or business but not at work 
 Looking for work 
 Working, but not for pay, at a family-owned job or business 
 Not working at a job or business 
 Not looking for work 
 Taking care of house or family 
 Going to school 
 Retired 
 Disabled 
 Other:  
 
 Prefer not to answer 
 Don’t know 
8. *What was your household’s total family income (before taxes) from all sources in the last 
year? (Check one) 
 Less than $10,000 
 $10,000 to $14,999 
 $15,000 to $19,999 
 $20,000 to $24,999 
 $25,000 to $29,999 
 $30,000 to $39,999 
 $40,000 to $49,999 
 $50,000 to $59,999 

SouthSeq Baseline/Enrollment Survey (deceased proband) 
* indicates required question 
 
 $60,000 to $69,999 
 $70,000 to $79,999 
 $80,000 to $99,999 
 $100,000 to $119,999 
 $120,000 to $139,999 
 $140,000 or more 
 Prefer not to answer 
9. 
How many people (children and adults) were supported by this income in the last year?  
 
 
 
10. *What is the highest grade or level of school you completed or the highest degree you 
received? (Check one) 
 No schooling completed 
 Elementary school (kindergarten through 5th grade) 
 Middle school (6th, 7th, or 8th grade) 
 Some high school (9th, 10th, or 11th grade) 
 12th grade, no diploma 
 High school graduate (diploma or GED or equivalent) 
 Some post-high school training (college or occupational, technical, or vocational training), no 
degree or certificate 
 Completed occupational, technical, or vocational program, received degree or certificate 
 Associate (2-year) college degree 
 Bachelor’s degree (for example: BA, AB, BS) 
 Master’s degree (for example: MA, MS, MEng, MEd, MSW, MBA) 
 Professional degree (for example: MD, DDS, DVM, LLB, JD) 
 Doctoral degree (for example: PhD, EdD) 
 
11. *Are you covered by health insurance or some other kind of health care plan? (Include health 
insurance obtained through employment or purchased directly, as well as government programs 
like Medicare and Medicaid that provide medical care or help pay medical bills) (Check one) 
 No 
 Yes 
12. If you answered yes for #11: What kind or kinds of health insurance or health care coverage do you 
have? (Check all that apply) 
 Private health insurance, employment based 
 Private health insurance, directly purchased 
 Government plan, Medicare 
 Government plan, Medicaid 
 Government plan, Military health care 
 Other type of insurance (Please Describe):  
 
 No coverage of any type. 

SouthSeq Baseline/Enrollment Survey (deceased proband) 
* indicates required question 
 
 
13. *Which of the following currently applies to your child? 
 My child is currently in the hospital 
 My child is now living outside the hospital 
 My child is no longer living 
 
14. *Considering your child’s medical condition, please rank the degree to which you agree 
with the following statements: 
 
Strongly 
Disagree 
Disagree 
Somewhat 
Disagree 
Neutral Somewhat 
Agree 
Agree Strongly 
Agree 
I am clear in my own 
mind why my family 
has enrolled in 
SouthSeq. 
I can explain what the 
condition means to 
people in my family 
who may need to 
know. 
I understand the 
impact of the condition 
on any child I may 
have. 
When I think about the 
condition in my family, 
I get upset. 
I don’t know where to 
go to get the medical 
help I/my family need 
(s). 
I can control how this 
condition affects my 
family. 
I feel positive about 
the future. 
I am able to cope with 
having this condition 
in my family. 
I don’t know what 
could be gained from 
each of the options 
available to me. 
Having this condition 
in my family makes 
me feel anxious. 

SouthSeq Baseline/Enrollment Survey (deceased proband) 
* indicates required question 
 
I don’t know if this 
condition could affect 
my other relatives 
(brothers, sisters, 
aunts, uncles, 
cousins). 
In relation to the 
condition in my family, 
nothing I decide will 
change the future for 
any children I might 
have. 
I understand the 
reasons why my 
child’s doctor referred 
my family to SouthSeq 
I know how to get the 
non-medical help I/my 
family need(s) (e.g. 
educational, financial, 
social support). 
I can explain what the 
condition means to 
people outside my 
family who may need 
to know (e.g. 
teachers, social 
workers). 
I don’t know what I 
can do to change how 
this condition affects 
me/my children. 
I don’t know who else 
in my family might be 
at risk for this 
condition. 
I am able to make 
plans for the future. 
I feel guilty because I 
(might have) passed 
this condition on to my 
children. 
I am powerless to do 
anything about this 
condition in my family. 
I understand what 
concerns led to my 
referral to SouthSeq 
I can make decisions 
about the condition 
that may change the 

SouthSeq Baseline/Enrollment Survey (deceased proband) 
* indicates required question 
 
future of any child(ren) 
I may have. 
 
 
15. For each item, rate yourself on the scale from “Not at all Good (1) to Extremely good (6)” 
 
 
a. How good are you at working with fractions? 
 
Not at all 
good 
Extremely 
Good 
1 
2 
3 
4 
5 
6 
b. How good are you at figuring out how much a shirt will cost if it is 25% off? 
 
Not at all 
good 
Extremely 
Good 
1 
2 
3 
4 
5 
6 
c. How often do you find numerical information to be useful? 
 
Never 
Very often 
1 
2 
3 
4 
5 
6 
 
 
16. *Please mark the following statements as True or False. 
 
True 
False 
It is possible to see a gene with the naked eye. 
Healthy parents can have a child with a hereditary disease. 
The onset of certain diseases is due to genes, environment and 
lifestyle. 
The carrier of a disease gene may be completely healthy. 
All serious diseases are hereditary. 
Genes are inside cells. 
The child of a disease gene carrier is always also a carrier of the 
same disease. 
A gene is a piece of DNA. 
A gene is part of a chromosome. 
All body parts have all of the same genes. 
It has been estimated that a person has about 20,000 genes. 
A person’s race and ethnicity can affect how likely they are to get a 
disease. 
Each of us has variations in our genes that make it more likely that 
we will get certain diseases. 
A “complex disease” is a health condition brought on by many 
genes and lifestyle and environment. 
A single nucleotide polymorphism or “SNiP” is a variation present in 
some individuals that stretches across a large section of DNA. 

SouthSeq Baseline/Enrollment Survey (deceased proband) 
* indicates required question 
 
 
 
 
17. *Please rank the degree to which you agree with the following statements 
 
 
Always 
Often 
Sometimes Occasionally 
Never 
How often do you have 
someone (like a family 
member, friend, hospital/clinic 
worker, or caregiver) help you 
read medical materials? 
How often do you have 
problems learning about your 
medical condition because of 
difficulty reading written 
information? 
How often do you have a 
problem understanding what 
is told to you about your 
medical condition? 
Not at all 
A little bit 
Somewhat 
Quite a bit 
Extremely 
How confident are you filling 
out forms by yourself? 
 
 
18. *In general, would you say your health is: 
 
Excellent 
Very Good 
Good 
Fair 
Poor 
 
 
 
19. *Here are some questions about the support that is available to you. 
a. About how many close friends and close relatives do you have (people you feel at ease with 
and can talk to about what is on your mind)? 
Write in number of close friends and close relatives: 
 
 
b. People sometimes look to others for companionship, assistance, or other types of support. How 
often is each of the following kinds of support available to YOU if you need it? 
 
None of 
the time 
A little of 
the time 
Some of 
the time 
Most of 
the time 
All of the 
time 
Someone to help you if you were 
confined to bed… 
Someone you can count on to listen 
to you when you need to talk… 

SouthSeq Baseline/Enrollment Survey (deceased proband) 
* indicates required question 
 
Someone to give you good advice 
about a crisis… 
Someone to take you to the doctor if 
you needed it… 
Someone who shows you love and 
affection… 
Someone to have a good time with… 
Someone to give you information to 
help you understand a situation… 
Someone to confide in or talk to 
about yourself or your problems… 
Someone who hugs you… 
Someone to get together with for 
relaxation… 
Someone to prepare your meals if 
you were unable to do it yourself… 
Someone whose advice you really 
want… 
Someone to do things with to help 
you get your mind off things… 
Someone to help with daily chores if 
you were sick… 
Someone to share your most private 
worries and fears with… 
Someone to turn to for suggestions 
about how to deal with a personal 
problem… 
Someone to do something enjoyable 
with… 
Someone who understands your 
problems… 
Someone to love and make you feel 
wanted… 

 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 7.2 
ROR Survey 

SouthSeq Return of Results (ROR) Survey 
* indicates required question 
 
1. *Please identify the individual completing this survey. 
 Mother 
 Father 
 Other (please specify):  
 
 
2. *What is your age? 
 
 
3. *In the past 3 months, has your marital status or employment changed? 
 Yes 
 No 
4. 
If you answered yes to question 3: Are you currently (please select one): 
 Married 
 Living together but not married 
 Separated or Divorced 
 Widowed 
 Never married and currently not living together 
5. 
If answered yes to question 3: What is your employment status from this past week? (select 
all that apply) 
 No change 
 Working for pay at a job or business 
 With a job or business but not at work 
 Looking for work 
 Working, but not for pay, at a family-owned job or business 
 Not working at a job or business 
 Not looking for work 
 Taking care of house or family 
 Going to school 
 Retired 
 Disabled 
 Other:  
 
 Refused 
 Don’t know 
 
 
6. Is your child covered by health insurance or some other kind of health care plan? 
(Include health insurance obtained through employment or purchased directly as well as 
government programs like Medicare and Medicaid that provide medical care or help pay 
medical bills) (Check one) 
 No 
 Yes 

SouthSeq Return of Results (ROR) Survey 
* indicates required question 
 
7. If you answered yes for #6: IF YOUR CHILD IS COVERED: What kind or kinds of health 
insurance or health care coverage do they have? (Check all that apply) 
 Private health insurance, employment based 
 Private health insurance, directly purchased 
 Government plan, Medicare 
 Government plan, Medicaid 
 Government plan, Military health care 
 Other type of insurance (Please Describe):  
 
 No coverage of any type. 
 
8. *In the past 3 months, has your residential address changed? 
 Yes (if yes, please notify your study coordinator) 
 No 
 
9. *Which of the following currently applies to your child? 
 My child is currently in the hospital 
 My child is now living outside the hospital 
 My child is no longer living (if selected, skip to Question 11) 

10. How good is your child’s health TODAY? 
SouthSeq Return of Results (ROR) Survey 
* indicates required question 
 
 
 
 
 
• We would like know how good or bad your 
child’s health is TODAY. 
• This line is numbered 0 to 100. 
• 100 means the best health you can imagine. 
0 means the worst health you can imagine. 
• Mark an X on the scale to indicate how your 
child’s health is TODAY 
• Now please write the number you marked on 
the scale in the box below 
 
 
 
 
 
 
YOUR CHILD’S HEALTH TODAY=  
 
o N/A 

SouthSeq Return of Results (ROR) Survey 
* indicates required question 
 
11. *Considering your child’s medical condition, please rank the degree to which you 
agree with the following statements: 
 
Strongly 
Disagree 
Disagree 
Somewhat 
Disagree 
Neutral Somewhat 
Agree 
Agree 
Strongly 
Agree 
I am clear in my own 
mind why my family 
has enrolled in 
SouthSeq. 
I can explain what the 
condition means to 
people in my family 
who may need to 
know. 
I understand the 
impact of the condition 
on my child(ren)/any 
child I may have. 
When I think about the 
condition in my family, 
I get upset. 
I don’t know where to 
go to get the medical 
help I/my family need 
(s). 
I can see that good 
things have come 
from having this 
condition in my family. 
I can control how this 
condition affects my 
family. 
I feel positive about 
the future. 
I am able to cope with 
having this condition 
in my family. 
I don’t know what 
could be gained from 
each of the options 
available to me. 
Having this condition 
in my family makes 
me feel anxious. 
I don’t know if this 
condition could affect 
my other relatives 
(brothers, sisters, 
aunts, uncles, 
cousins). 

SouthSeq Return of Results (ROR) Survey 
* indicates required question 
 
In relation to the 
condition in my family, 
nothing I decide will 
change the future for 
my children/any 
children I might have. 
I understand the 
reasons why my 
child’s doctor referred 
my family to SouthSeq 
I know how to get the 
non-medical help I/my 
family need(s) (e.g. 
educational, financial, 
social support). 
I can explain what the 
condition means to 
people outside my 
family who may need 
to know (e.g. 
teachers, social 
workers). 
I don’t know what I 
can do to change how 
this condition affects 
me/my children. 
I don’t know who else 
in my family might be 
at risk for this 
condition. 
I am hopeful that my 
child(ren) can look 
forward to a rewarding 
family life. 
I am able to make 
plans for the future. 
I feel guilty because I 
(might have) passed 
this condition on to my 
children. 
I am powerless to do 
anything about this 
condition in my family. 
I understand what 
concerns led to my 
referral to SouthSeq 
I can make decisions 
about the condition 
that may change my 
child(ren)’s future/the 

SouthSeq Return of Results (ROR) Survey 
* indicates required question 
 
future of any child(ren) 
I may have. 
12. *The following questions ask about how you, as a parent, felt after receiving your 
child’s genetic test results. Please indicate how much you had each specific feeling in 
the past week by choosing the one answer for each question. 
 
Not at all 
A little 
Somewhat 
A good 
deal 
A great 
deal 
How upset did you feel 
about your child’s genetic 
test result? 
How happy did you feel 
about your child’s genetic 
test result? 
How anxious or nervous 
did you feel about your 
child’s genetic test result? 
How relieved did you feel 
about your child’s genetic 
test result? 
How sad did you feel about 
your child’s genetic test 
result? 
How frustrated did you feel 
about recommendations for 
your child’s care based on 
the genetic test? 
How uncertain did you feel 
about what your child’s 
genetic test result means for 
your child? 
How uncertain did you feel 
about what your child’s 
genetic test result means for 
other family members’ risk of 
disease? 
How much did you feel that 
you understood clearly 
your child’s choices for 
care based on the genetic 
test result? 
How concerned did you feel 
that your child’s genetic test 
result would affect his or her 
ability to get or keep health 
insurance? 
How helpful was the 
information you received 
from your genetic test result 

SouthSeq Return of Results (ROR) Survey 
* indicates required question 
 
in planning for your child’s 
future? 
How concerned did you feel 
that your child’s genetic test 
result might make it hard for 
them to get or keep a job? 
How guilty did you feel 
about your child’s genetic 
test result? 
How much loss of control 
over your child’s life did you 
feel because of your child’s 
genetic test result? 
 
 
13. *Rate how certain you feel about the following aspects of your child’s sequence 
results: 
 
Very 
Uncertain (1) 
2 
3 
4 
Very 
Certain (5) 
What my child’s test 
results mean for 
his/her health 
What actions I need 
to take based on my 
child’s test results 
How my child’s 
doctor may use the 
results to improve 
my child’s health 
Whether I am 
worried or 
concerned about my 
child’s test results 
Whether my child’s 
test results revealed 
something alarming 
Whether my child’s 
test results 
disrupted my life 
Whether I can trust 
my child’s test 
results 
Whether my child’s 
test results are 
accurate 

SouthSeq Return of Results (ROR) Survey 
* indicates required question 
 
14. *Please indicate how useful you find the following outcomes of genome sequencing 
for you and your child 
 
Not at 
all 
useful 
(1) 
A little 
useful 
(2) 
Somewhat 
useful (3) 
Neutral 
(4) 
Useful 
(5) 
Very 
useful 
(6) 
Extremely 
useful 
(7) 
Help with my 
child’s life planning 
Inform plans for 
my child’s school 
or career 
Inform my child’s 
decisions about 
having children 
Use for testing a 
future pregnancy, 
if appropriate 
Help me or our 
family mentally 
prepare for the 
future 
Help to better 
understand my 
child’s health 
Contribute to my 
child’s self- 
knowledge 
Help me cope with 
my child’s health 
risks 
Help me feel more 
in control of my 
child’s health 
Help me feel more 
in control of my 
child’s life 
Simply to provide 
information 
Satisfy my 
curiosity about my 
child 
Help my child use 
social programs, 
like resources and 
services 
Improve 
communication 
with my family 
members 

SouthSeq Return of Results (ROR) Survey 
* indicates required question 
 
Feel good about 
helping the 
medical 
community 
Feel good about 
having information 
for family 
members 
Feel good about 
taking 
responsibility for 
my child’s health 
 
 
15. *In general, would you say your health is: 
 
Excellent 
Very Good 
Good 
Fair 
Poor 
 
 
 
16. How well do you understand your child’s test results? 
 
Not at all 
A little bit 
Moderately 
Quite a bit 
Extremely 
 
 
 
 
17. *Please tell us about your experience receiving your child’s genetic test results. 
Strongly 
Disagree 
Disagree 
Neither 
Agree nor 
Disagree 
Agree 
Strongly 
Agree 
Not 
Applicable 
I was treated with 
sensitivity and 
respect. 
I felt listened to. 
The clinical team 
checked to make 
sure I understood 
the information 
I trust the clinical 
team 
The clinical team 
explained 
complicated topics 
well 

SouthSeq Return of Results (ROR) Survey 
* indicates required question 
 
I got clear, 
understandable 
information. 
I received too much 
information to 
understand 
It was hard to make 
sense out of the 
information 
I felt I had the 
information and 
support available to 
me to answer any 
questions I had 
after receiving my 
child’s genetic 
results 
I felt comfortable 
asking questions 
and voicing my 
concerns 
The clinical team 
helped me cope 
with any uncertainty 
or unknowns 
It was hard to ask 
questions about this 
information 
I felt comfortable 
talking about 
sensitive issues or 
embarrassing 
subjects with the 
clinical team 
The clinical team 
noticed when I had 
problems 
understanding 
I had questions 
about this 
information that I 
was unable to ask 

SouthSeq Return of Results (ROR) Survey 
* indicates required question 
 
18. *Here are some questions about the support that is available to you 
a. About how many close friends and close relatives do you have (people you feel at 
ease with and can talk to about what is on your mind)? 
 
Write in number of close friends and close relatives: 
 
b. People sometimes look to others for companionship, assistance, or other types of 
support. How often is each of the following kinds of support available to YOU if you 
need it? 
 
None of 
the time 
A little of 
the time 
Some of 
the time 
Most of 
the time 
All of the 
time 
Someone to help you if you were 
confined to bed… 
Someone you can count on to listen 
to you when you need to talk… 
Someone to give you good advice 
about a crisis… 
Someone to take you to the doctor if 
you needed it… 
Someone who shows you love and 
affection… 
Someone to have a good time with… 
Someone to give you information to 
help you understand a situation… 
Someone to confide in or talk to 
about yourself or your problems… 
Someone who hugs you… 
Someone to get together with for 
relaxation… 
Someone to prepare your meals if 
you were unable to do it yourself… 
Someone whose advice you really 
want… 
Someone to do things with to help 
you get your mind off things… 
Someone to help with daily chores if 
you were sick… 
Someone to share your most private 
worries and fears with… 
Someone to turn to for suggestions 
about how to deal with a personal 
problem… 
Someone to do something enjoyable 
with… 
Someone who understands your 
problems… 
Someone to love and make you feel 
wanted… 

SouthSeq Return of Results (ROR) Survey 
* indicates required question 
 
Information Seeking V1 (ROR) 
19. *What sources, if any do you think you are likely to use to find more information 
about the genetic test results you received today? Please write below. 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 7.2A 
ROR Survey for Deceased Probands 

SouthSeq Return of Results (ROR) Survey (deceased proband) 
* indicates required question 
 
 
1. *Please identify the individual completing this survey. 
 Mother 
 Father 
 Other (please specify):  
 
 
2. *What is your age? 
 
 
3. *In the past 3 months, has your marital status or employment changed? 
 Yes 
 No 
4. 
If you answered yes to question 3: Are you currently (please select one): 
 Married 
 Living together but not married 
 Separated or Divorced 
 Widowed 
 Never married and currently not living together 
5. 
If answered yes to question 3: What is your employment status from this past week? (select all that 
apply) 
 No change 
 Working for pay at a job or business 
 With a job or business but not at work 
 Looking for work 
 Working, but not for pay, at a family-owned job or business 
 Not working at a job or business 
 Not looking for work 
 Taking care of house or family 
 Going to school 
 Retired 
 Disabled 
 Other:  
 
 Refused 
 Don’t know 
 
 
6. *In the past 3 months, has your residential address changed? 
 Yes (if yes, please notify your study coordinator) 
 No 
 
7. *Which of the following currently applies to your child? 
 My child is currently in the hospital 

SouthSeq Return of Results (ROR) Survey (deceased proband) 
* indicates required question 
 
 My child is now living outside the hospital 
 My child is no longer living 
 
8. *Considering your child’s medical condition, please rank the degree to which you agree with 
the following statements: 
 
Strongly 
Disagree 
Disagree 
Somewhat 
Disagree 
Neutral Somewhat 
Agree 
Agree 
Strongly 
Agree 
I am clear in my own 
mind why my family 
has enrolled in 
SouthSeq. 
I can explain what the 
condition means to 
people in my family 
who may need to 
know. 
I understand the 
impact of the condition 
on any child I may 
have. 
When I think about the 
condition in my family, 
I get upset. 
I don’t know where to 
go to get the medical 
help I/my family need 
(s). 
I can control how this 
condition affects my 
family. 
I feel positive about 
the future. 
I am able to cope with 
having this condition 
in my family. 
I don’t know what 
could be gained from 
each of the options 
available to me. 
Having this condition 
in my family makes 
me feel anxious. 
I don’t know if this 
condition could affect 
my other relatives 
(brothers, sisters, 
aunts, uncles, 
cousins). 

SouthSeq Return of Results (ROR) Survey (deceased proband) 
* indicates required question 
 
In relation to the 
condition in my family, 
nothing I decide will 
change the future for 
any children I might 
have. 
I understand the 
reasons why my 
child’s doctor referred 
my family to SouthSeq 
I know how to get the 
non-medical help I/my 
family need(s) (e.g. 
educational, financial, 
social support). 
I can explain what the 
condition means to 
people outside my 
family who may need 
to know (e.g. 
teachers, social 
workers). 
I don’t know what I 
can do to change how 
this condition affects 
me/my children. 
I don’t know who else 
in my family might be 
at risk for this 
condition. 
I am able to make 
plans for the future. 
I feel guilty because I 
(might have) passed 
this condition on to my 
children. 
I am powerless to do 
anything about this 
condition in my family. 
I understand what 
concerns led to my 
referral to SouthSeq 
I can make decisions 
about the condition 
that may change the 
future of any child(ren) 
I may have. 

SouthSeq Return of Results (ROR) Survey (deceased proband) 
* indicates required question 
 
9. *The following questions ask about how you, as a parent, felt after receiving your child’s 
genetic test results. Please indicate how much you had each specific feeling in the past 
week by choosing the one answer for each question. 
 
Not at all 
A little 
Somewhat 
A good 
deal 
A great 
deal 
How upset did you feel about 
your child’s genetic test 
result? 
How happy did you feel about 
your child’s genetic test 
result? 
How anxious or nervous did 
you feel about your child’s 
genetic test result? 
How relieved did you feel 
about your child’s genetic test 
result? 
How sad did you feel about 
your child’s genetic test 
result? 
How uncertain did you feel 
about what your child’s 
genetic test result means for 
other family members’ risk of 
disease? 
How guilty did you feel about 
your child’s genetic test 
result? 
 
 
 
10. *Please indicate how useful you find the following outcomes of genome sequencing for you 
and your child 
 
Not at 
all 
useful 
(1) 
A little 
useful 
(2) 
Somewhat 
useful (3) 
Neutral 
(4) 
Useful 
(5) 
Very 
useful 
(6) 
Extremely 
useful 
(7) 
Use for testing a 
future pregnancy, if 
appropriate 
Help me or our family 
mentally prepare for 
the future 
Simply to provide 
information 
Improve 
communication with 
my family members 

SouthSeq Return of Results (ROR) Survey (deceased proband) 
* indicates required question 
 
Feel good about 
helping the medical 
community 
Feel good about 
having information for 
family members 
 
 
11. *In general, would you say your health is: 
 
Excellent 
Very Good 
Good 
Fair 
Poor 
 
 
 
12. How well do you understand your child’s test results? 
 
Not at all 
A little bit 
Moderately 
Quite a bit 
Extremely 
 
 
 
 
13. *Please tell us about your experience receiving your child’s genetic test results. 
Strongly 
Disagree 
Disagree 
Neither 
Agree nor 
Disagree 
Agree 
Strongly 
Agree 
Not 
Applicable 
I was treated with 
sensitivity and 
respect. 
I felt listened to. 
The clinical team 
checked to make 
sure I understood 
the information 
I trust the clinical 
team 
The clinical team 
explained 
complicated topics 
well 
I got clear, 
understandable 
information. 
I received too much 
information to 
understand 

SouthSeq Return of Results (ROR) Survey (deceased proband) 
* indicates required question 
 
It was hard to make 
sense out of the 
information 
I felt I had the 
information and 
support available to 
me to answer any 
questions I had 
after receiving my 
child’s genetic 
results 
I felt comfortable 
asking questions 
and voicing my 
concerns 
The clinical team 
helped me cope 
with any uncertainty 
or unknowns 
It was hard to ask 
questions about this 
information 
I felt comfortable 
talking about 
sensitive issues or 
embarrassing 
subjects with the 
clinical team 
The clinical team 
noticed when I had 
problems 
understanding 
I had questions 
about this 
information that I 
was unable to ask 
 
 
 
 
14. *Here are some questions about the support that is available to you 
a. About how many close friends and close relatives do you have (people you feel at ease with 
and can talk to about what is on your mind)? 
Write in number of close friends and close relatives: 
 
 
b. People sometimes look to others for companionship, assistance, or other types of support. 
How often is each of the following kinds of support available to YOU if you need it? 

SouthSeq Return of Results (ROR) Survey (deceased proband) 
* indicates required question 
 
None of 
the time 
A little of 
the time 
Some of 
the time 
Most of 
the time 
All of the 
time 
Someone to help you if you were 
confined to bed… 
Someone you can count on to listen 
to you when you need to talk… 
Someone to give you good advice 
about a crisis… 
Someone to take you to the doctor if 
you needed it… 
Someone who shows you love and 
affection… 
Someone to have a good time with… 
Someone to give you information to 
help you understand a situation… 
Someone to confide in or talk to 
about yourself or your problems… 
Someone who hugs you… 
Someone to get together with for 
relaxation… 
Someone to prepare your meals if 
you were unable to do it yourself… 
Someone whose advice you really 
want… 
Someone to do things with to help 
you get your mind off things… 
Someone to help with daily chores if 
you were sick… 
Someone to share your most private 
worries and fears with… 
Someone to turn to for suggestions 
about how to deal with a personal 
problem… 
Someone to do something enjoyable 
with… 
Someone who understands your 
problems… 
Someone to love and make you feel 
wanted… 
 
 
Information Seeking V1 (ROR) 
15. *What sources, if any do you think you are likely to use to find more information about 
the genetic test results you received today? Please write below. 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 7.3 1‐
month post‐ROR Survey 

SouthSeq 1‐month post‐ROR Survey 
 
1. Please identify the individual completing this survey. 
o Mother 
o Father 
o Other (please specify):  
 
 
2. In the past 3 months, has your marital status or employment changed? 
o Yes 
o No 
If you answered yes to question 2: 
 
3. Are you currently (please select one): 
 Married 
 Living together but not married 
 Separated or Divorced 
 Widowed 
 Never married and currently not living together 
If answered yes to question 2: 
4. What is your employment status from this past week? (select all that apply) 
 No change 
 Working for pay at a job or business 
 With a job or business but not at work 
 Looking for work 
 Working, but not for pay, at a family-owned job or business 
 Not working at a job or business 
 Not looking for work 
 Taking care of house or family 
 Going to school 
 Retired 
 Disabled 
 Other:  
 
 Refused 
 Don’t know 
5. In the past month, has your residential address changed? 
 Yes 
 No 
If you answered yes to question 5: 
6. What is the address where you currently live? 
Street:  
 
 
City: 
 
 
State:  
 
Zip Code:  
 

SouthSeq 1‐month post‐ROR Survey 
 
7. In the past month, has your child’s residential address changed? 
 Yes 
 No 
If you answered yes to question 7: 
8. What is the address where your child currently lives? 
 
Street:  
 
 
City: 
 
 
State:  
 
Zip Code:  
 

How good is your child’s health TODAY? 
SouthSeq 1‐month post‐ROR Survey 
 
 
 
 
 
• We would like know how good or bad your 
child’s health is TODAY. 
• This line is numbered 0 to 100. 
• 100 means the best health you can imagine. 
0 means the worst health you can imagine. 
• Mark an X on the scale to indicate how your 
child’s health is TODAY 
• Now please write the number you marked on 
the scale in the box below 
 
 
 
 
 
 
YOUR CHILD’S HEALTH TODAY=  
 
o N/A 

SouthSeq 1‐month post‐ROR Survey 
 
9. Considering your child’s medical condition, please rank the degree to which you 
agree with the following statements: 
 
Strongly 
Disagree 
Disagree 
Somewhat 
Disagree 
Neutral Somewhat 
Agree 
Agree 
Strongly 
Agree 
I am clear in my own 
mind why my family 
has enrolled in 
SouthSeq. 
I can explain what the 
condition means to 
people in my family 
who may need to 
know. 
I understand the 
impact of the condition 
on my child(ren)/any 
child I may have. 
When I think about the 
condition in my family, 
I get upset. 
I don’t know where to 
go to get the medical 
help I/my family need 
(s). 
I can see that good 
things have come 
from having this 
condition in my family. 
I can control how this 
condition affects my 
family. 
I feel positive about 
the future. 
I am able to cope with 
having this condition 
in my family. 
I don’t know what 
could be gained from 
each of the options 
available to me. 
Having this condition 
in my family makes 
me feel anxious. 
I don’t know if this 
condition could affect 
my other relatives 
(brothers, sisters, 
aunts, uncles, 
cousins). 

SouthSeq 1‐month post‐ROR Survey 
 
In relation to the 
condition in my family, 
nothing I decide will 
change the future for 
my children/any 
children I might have. 
I understand the 
reasons why my 
child’s doctor referred 
my family to SouthSeq 
I know how to get the 
non-medical help I/my 
family need(s) (e.g. 
educational, financial, 
social support). 
I can explain what the 
condition means to 
people outside my 
family who may need 
to know (e.g. 
teachers, social 
workers). 
I don’t know what I 
can do to change how 
this condition affects 
me/my children. 
I don’t know who else 
in my family might be 
at risk for this 
condition. 
I am hopeful that my 
child(ren) can look 
forward to a rewarding 
family life. 
I am able to make 
plans for the future. 
I feel guilty because I 
(might have) passed 
this condition on to my 
children. 
I am powerless to do 
anything about this 
condition in my family. 
 
 
10. The following questions ask about how you, as a parent, felt after receiving your child’s 
genetic test results. Please indicate how much you had each specific feeling in the past 
week by choosing the one answer for each question. 

SouthSeq 1‐month post‐ROR Survey 
 
Not at all 
A little 
Somewhat 
A good 
deal 
A great 
deal 
How upset did you feel 
about your child’s genetic 
test result? 
How happy did you feel 
about your child’s genetic 
test result? 
How anxious or nervous 
did you feel about your 
child’s genetic test result? 
How relieved did you feel 
about your child’s genetic 
test result? 
How sad did you feel about 
your child’s genetic test 
result? 
How frustrated did you feel 
about recommendations for 
your child’s care based on 
the genetic test? 
How uncertain did you feel 
about what your child’s 
genetic test result means for 
your child? 
How uncertain did you feel 
about what your child’s 
genetic test result means for 
other family members’ risk of 
disease? 
How much did you feel that 
you understood clearly 
your child’s choices for 
care based on the genetic 
test result? 
How concerned did you feel 
that your child’s genetic test 
result would affect his or her 
ability to get or keep health 
insurance? 
How helpful was the 
information you received 
from your genetic test result 
in planning for your child’s 
future? 
How concerned did you feel 
that your child’s genetic test 
result might make it hard for 
them to get or keep a job? 

SouthSeq 1‐month post‐ROR Survey 
 
How guilty did you feel 
about your child’s genetic 
test result? 
How much loss of control 
over your child’s life did you 
feel because of your child’s 
genetic test result? 
 
 
11. Rate how certain you feel about the following aspects of your child’s sequence 
results: 
 
Very 
Uncertain (1) 
2 
3 
4 
Very 
Certain (5) 
What my child’s test 
results mean for 
his/her health 
What actions I need 
to take based on my 
child’s test results 
How my child’s 
doctor may use the 
results to improve 
my child’s health 
Whether I am 
worried or 
concerned about my 
child’s test results 
Whether my child’s 
test results revealed 
something alarming 
Whether my child’s 
test results 
disrupted my life 
Whether I can trust 
my child’s test 
results 
Whether my child’s 
test results are 
accurate 
 
 
12. Please indicate how useful you find the following outcomes of genome sequencing 
for you and your child 
 
Not at 
A little 
Somewhat 
Neutral 
Useful 
Very 
Extremely 
all 
useful 
useful (3) 
(4) 
(5) 
useful 
useful 
useful 
(2) 
(6) 
(7) 
(1) 

SouthSeq 1‐month post‐ROR Survey 
 
Help with my 
child’s life planning 
Inform plans for 
my child’s school 
or career 
Inform my child’s 
decisions about 
having children 
Use for testing a 
future pregnancy, 
if appropriate 
Help me or our 
family mentally 
prepare for the 
future 
Help to better 
understand my 
child’s health 
Contribute to my 
child’s self- 
knowledge 
Help me cope with 
my child’s health 
risks 
Help me feel more 
in control of my 
child’s health 
Help me feel more 
in control of my 
child’s life 
Simply to provide 
information 
Satisfy my 
curiosity about my 
child 
Help my child use 
social programs, 
like resources or 
services 
Improve 
communication 
with my family 
members 
Feel good about 
helping the 
medical 
community 
Feel good about 
having information 
for family 
members 

SouthSeq 1‐month post‐ROR Survey 
 
Feel good about 
taking 
responsibility for 
my child’s health 
 
 
13. 
a. In general, would you say your health is: 
 
Excellent 
Very Good 
Good 
Fair 
Poor 
 
 
 
14. 
How well do you understand your child’s test results? 
 
Not at all 
A little bit 
Moderately 
Quite a bit 
Extremely 
 
 
 
15. 
Please tell us about your experience receiving your child’s genetic test results. 
 
Strongly 
Disagree Disagree 
Neither Agree 
nor Disagree 
Agree 
Strongly 
Agree 
Not 
Applicable 
I was treated 
with sensitivity 
and respect. 
I felt listened 
to. 
The clinical 
team checked 
to make sure I 
understood the 
information 
I trust the 
clinical team 
The clinical 
team explained 
complicated 
topics well 
I got clear, 
understandable 
information. 
I received too 
much 
information to 
understand 

SouthSeq 1‐month post‐ROR Survey 
 
It was hard to 
make sense 
out of the 
information 
I felt I had the 
information and 
support 
available to me 
to answer any 
questions I had 
after receiving 
my child’s 
genetic results 
I felt 
comfortable 
asking 
questions and 
voicing my 
concerns 
The clinical 
team helped 
me cope with 
any uncertainty 
or unknowns 
It was hard to 
ask questions 
about this 
information 
I felt 
comfortable 
talking about 
sensitive 
issues or 
embarrassing 
subjects with 
the clinical 
team 
The clinical 
team noticed 
when I had 
problems 
understanding 
I had questions 
about this 
information that 
I was unable to 
ask 

SouthSeq 1‐month post‐ROR Survey 
 
16. 
Here are some questions about the support that is available to you 
a. About how many close friends and close relatives do you have (people you feel at 
ease with and can talk to about what is on your mind)? 
 
Write in number of close friends and close relatives: 
 
b. People sometimes look to others for companionship, assistance, or other types of 
support. How often is each of the following kinds of support available to YOU if you 
need it? 
 
None of 
the time 
A little of 
the time 
Some of 
the time 
Most of 
the time 
All of the 
time 
Someone to help you if you were 
confined to bed… 
Someone you can count on to listen 
to you when you need to talk… 
Someone to give you good advice 
about a crisis… 
Someone to take you to the doctor if 
you needed it… 
Someone who shows you love and 
affection… 
Someone to have a good time with… 
Someone to give you information to 
help you understand a situation… 
Someone to confide in or talk to 
about yourself or your problems… 
Someone who hugs you… 
Someone to get together with for 
relaxation… 
Someone to prepare your meals if 
you were unable to do it yourself… 
Someone whose advice you really 
want… 
Someone to do things with to help 
you get your mind off things… 
Someone to help with daily chores if 
you were sick… 
Someone to share your most private 
worries and fears with… 
Someone to turn to for suggestions 
about how to deal with a personal 
problem… 
Someone to do something enjoyable 
with… 
Someone who understands your 
problems… 
Someone to love and make you feel 
wanted… 

SouthSeq 1‐month post‐ROR Survey 
 
 
17. Which of the following sources, if any, did you use to find more information about the genetic 
test results you received at your last visit? 
Please rate the usefulness of the sources you used. (1-not useful at all, 5=very useful) 
Not 
useful at 
all (1) 
2 
3 
4 
Very 
useful (5) 
N/A 
Family or friends 
ο 
ο 
ο 
ο 
ο 
ο 
Facebook 
ο 
ο 
ο 
ο 
ο 
ο 
Support groups 
ο 
ο 
ο 
ο 
ο 
ο 
My/my child’s other doctors 
ο 
ο 
ο 
ο 
ο 
ο 
Internet search (i.e. Google, 
PubMed, etc.) 
ο 
ο 
ο 
ο 
ο 
ο 
Books and other print media 
ο 
ο 
ο 
ο 
ο 
ο 
Information provided by the 
doctor who ordered my child’s 
genetic test 
ο 
ο 
ο 
ο 
ο 
ο 
Other (please specify): 
ο 
ο 
ο 
ο 
ο 
ο 
None 
ο 
ο 
ο 
ο 
ο 
ο 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 7.4 and 7.5 
4‐month and 4‐mont plus post‐ROR Survey 

SouthSeq 4‐month post‐ROR Survey 
 
1. Please identify the individual completing this survey. 
o Mother 
o Father 
o Other (please specify):  
 
 
2. In the past 3 months, has your marital status or employment changed? 
o Yes 
o No 
If you answered yes to question 2: 
 
3. Are you currently (please select one): 
 Married 
 Living together but not married 
 Separated or Divorced 
 Widowed 
 Never married and currently not living together 
If answered yes to question 2: 
4. What is your employment status from this past week? (select all that apply) 
 No change 
 Working for pay at a job or business 
 With a job or business but not at work 
 Looking for work 
 Working, but not for pay, at a family-owned job or business 
 Not working at a job or business 
 Not looking for work 
 Taking care of house or family 
 Going to school 
 Retired 
 Disabled 
 Other:  
 
 Refused 
 Don’t know 
5. In the past month, has your residential address changed? 
 Yes 
 No 
If you answered yes to question 5: 
6. What is the address where you currently live? 
Street:  
 
 
City: 
 
 
State:  
 
Zip Code:  
 

SouthSeq 4‐month post‐ROR Survey 
 
7. In the past month, has your child’s residential address changed? 
 Yes 
 No 
If you answered yes to question 7: 
8. What is the address where your child currently lives? 
 
Street:  
 
 
City: 
 
 
State:  
 
Zip Code:  
 

How good is your child’s health TODAY? 
SouthSeq 4‐month post‐ROR Survey 
 
 
 
 
 
• We would like know how good or bad your 
child’s health is TODAY. 
• This line is numbered 0 to 100. 
• 100 means the best health you can imagine. 
0 means the worst health you can imagine. 
• Mark an X on the scale to indicate how your 
child’s health is TODAY 
• Now please write the number you marked on 
the scale in the box below 
 
 
 
 
 
 
YOUR CHILD’S HEALTH TODAY=  
 
o N/A 

SouthSeq 4‐month post‐ROR Survey 
 
9. Considering your child’s medical condition, please rank the degree to which you 
agree with the following statements: 
 
Strongly 
Disagree 
Disagree 
Somewhat 
Disagree 
Neutral Somewhat 
Agree 
Agree 
Strongly 
Agree 
I am clear in my own 
mind why my family 
has enrolled in 
SouthSeq. 
I can explain what the 
condition means to 
people in my family 
who may need to 
know. 
I understand the 
impact of the condition 
on my child(ren)/any 
child I may have. 
When I think about the 
condition in my family, 
I get upset. 
I don’t know where to 
go to get the medical 
help I/my family need 
(s). 
I can see that good 
things have come 
from having this 
condition in my family. 
I can control how this 
condition affects my 
family. 
I feel positive about 
the future. 
I am able to cope with 
having this condition 
in my family. 
I don’t know what 
could be gained from 
each of the options 
available to me. 
Having this condition 
in my family makes 
me feel anxious. 
I don’t know if this 
condition could affect 
my other relatives 
(brothers, sisters, 
aunts, uncles, 
cousins). 

SouthSeq 4‐month post‐ROR Survey 
 
In relation to the 
condition in my family, 
nothing I decide will 
change the future for 
my children/any 
children I might have. 
I understand the 
reasons why my 
child’s doctor referred 
my family to SouthSeq 
I know how to get the 
non-medical help I/my 
family need(s) (e.g. 
educational, financial, 
social support). 
I can explain what the 
condition means to 
people outside my 
family who may need 
to know (e.g. 
teachers, social 
workers). 
I don’t know what I 
can do to change how 
this condition affects 
me/my children. 
I don’t know who else 
in my family might be 
at risk for this 
condition. 
I am hopeful that my 
child(ren) can look 
forward to a rewarding 
family life. 
I am able to make 
plans for the future. 
I feel guilty because I 
(might have) passed 
this condition on to my 
children. 
I am powerless to do 
anything about this 
condition in my family. 
 
 
10. The following questions ask about how you, as a parent, felt after receiving your child’s 
genetic test results. Please indicate how much you had each specific feeling in the past 
week by choosing the one answer for each question. 

SouthSeq 4‐month post‐ROR Survey 
 
Not at all 
A little 
Somewhat 
A good 
deal 
A great 
deal 
How upset did you feel 
about your child’s genetic 
test result? 
How happy did you feel 
about your child’s genetic 
test result? 
How anxious or nervous 
did you feel about your 
child’s genetic test result? 
How relieved did you feel 
about your child’s genetic 
test result? 
How sad did you feel about 
your child’s genetic test 
result? 
How frustrated did you feel 
about recommendations for 
your child’s care based on 
the genetic test? 
How uncertain did you feel 
about what your child’s 
genetic test result means for 
your child? 
How uncertain did you feel 
about what your child’s 
genetic test result means for 
other family members’ risk of 
disease? 
How much did you feel that 
you understood clearly 
your child’s choices for 
care based on the genetic 
test result? 
How concerned did you feel 
that your child’s genetic test 
result would affect his or her 
ability to get or keep health 
insurance? 
How helpful was the 
information you received 
from your genetic test result 
in planning for your child’s 
future? 
How concerned did you feel 
that your child’s genetic test 
result might make it hard for 
them to get or keep a job? 

SouthSeq 4‐month post‐ROR Survey 
 
How guilty did you feel 
about your child’s genetic 
test result? 
How much loss of control 
over your child’s life did you 
feel because of your child’s 
genetic test result? 
 
 
11. Rate how certain you feel about the following aspects of your child’s sequence 
 
a. In general, would you say your health is: 
 
Excellent 
Very Good 
Good 
Fair 
Poor 
 
 
 
12. 
How well do you understand your child’s test results? 
 
Not at all 
A little bit 
Moderately 
Quite a bit 
Extremely 
 
 
 
13. 
Please tell us about your experience receiving your child’s genetic test results. 
 
Strongly 
Disagree Disagree 
Neither Agree 
nor Disagree 
Agree 
Strongly 
Agree 
Not 
Applicable 
I was treated 
with sensitivity 
and respect. 
I felt listened 
to. 
The clinical 
team checked 
to make sure I 
understood the 
information 
I trust the 
clinical team 
The clinical 
team explained 
complicated 
topics well 
I got clear, 
understandable 
information. 

SouthSeq 4‐month post‐ROR Survey 
 
I received too 
much 
information to 
understand 
It was hard to 
make sense 
out of the 
information 
I felt I had the 
information and 
support 
available to me 
to answer any 
questions I had 
after receiving 
my child’s 
genetic results 
I felt 
comfortable 
asking 
questions and 
voicing my 
concerns 
The clinical 
team helped 
me cope with 
any uncertainty 
or unknowns 
It was hard to 
ask questions 
about this 
information 
I felt 
comfortable 
talking about 
sensitive 
issues or 
embarrassing 
subjects with 
the clinical 
team 
The clinical 
team noticed 
when I had 
problems 
understanding 
I had questions 
about this 
information that 
I was unable to 
ask 

SouthSeq 4‐month post‐ROR Survey 
 
14. 
Here are some questions about the support that is available to you 
a. About how many close friends and close relatives do you have (people you feel at 
ease with and can talk to about what is on your mind)? 
 
Write in number of close friends and close relatives: 
 
b. People sometimes look to others for companionship, assistance, or other types of 
support. How often is each of the following kinds of support available to YOU if you 
need it? 
 
None of 
the time 
A little of 
the time 
Some of 
the time 
Most of 
the time 
All of the 
time 
Someone to help you if you were 
confined to bed… 
Someone you can count on to listen 
to you when you need to talk… 
Someone to give you good advice 
about a crisis… 
Someone to take you to the doctor if 
you needed it… 
Someone who shows you love and 
affection… 
Someone to have a good time with… 
Someone to give you information to 
help you understand a situation… 
Someone to confide in or talk to 
about yourself or your problems… 
Someone who hugs you… 
Someone to get together with for 
relaxation… 
Someone to prepare your meals if 
you were unable to do it yourself… 
Someone whose advice you really 
want… 
Someone to do things with to help 
you get your mind off things… 
Someone to help with daily chores if 
you were sick… 
Someone to share your most private 
worries and fears with… 
Someone to turn to for suggestions 
about how to deal with a personal 
problem… 
Someone to do something enjoyable 
with… 
Someone who understands your 
problems… 
Someone to love and make you feel 
wanted… 

SouthSeq 4‐month post‐ROR Survey 
 
15. Which of the following sources, if any, did you use to find more information about the genetic 
test results you received at your last visit? 
Please rate the usefulness of the sources you used. (1-not useful at all, 5=very useful) 
Not 
useful at 
all (1) 
2 
3 
4 
Very 
useful (5) 
N/A 
Family or friends 
ο 
ο 
ο 
ο 
ο 
ο 
Facebook 
ο 
ο 
ο 
ο 
ο 
ο 
Support groups 
ο 
ο 
ο 
ο 
ο 
ο 
My/my child’s other doctors 
ο 
ο 
ο 
ο 
ο 
ο 
Internet search (i.e. Google, 
PubMed, etc.) 
ο 
ο 
ο 
ο 
ο 
ο 
Books and other print media 
ο 
ο 
ο 
ο 
ο 
ο 
Information provided by the 
doctor who ordered my child’s 
genetic test 
ο 
ο 
ο 
ο 
ο 
ο 
Other (please specify): 
ο 
ο 
ο 
ο 
ο 
ο 
None 
ο 
ο 
ο 
ο 
ο 
ο 
 
16. Since receiving your child’s study results, did you share the information with any biological 
family members (blood relatives)? 
o Yes 
o I didn’t share this information with anyone (if selected, skip to question 20) 
o I haven’t shared this information yet, but plan to in the future (if selected, skip to 
question 18) 
o I do not have blood relatives to share this information with (if selected, skip all 
remaining questions) 
 
17. Since receiving your child’s study results, have you shared the information with any of the 
following blood relatives? 
 
Yes 
No 
N/A 
My child’s other biologic parent 
ο 
ο 
ο 
My other child(ren) 
ο 
ο 
ο 
My siblings 
ο 
ο 
ο 
My parents 
ο 
ο 
ο 
My other biological family 
members 
(If yes) Please specify:  
 
ο 
ο 
ο 
 
18. On a scale of 1 to 5, how important were each of the following reasons for sharing your 
child’s genetic test results with blood relatives? 

SouthSeq 4‐month post‐ROR Survey 
 
Not at all 
important 
(1) 
2 
3 
4 
Very 
Important 
(5) 
To give my blood relatives 
information about their 
genetic risk 
ο 
ο 
ο 
ο 
ο 
To encourage my blood 
relatives to have genetic 
testing 
ο 
ο 
ο 
ο 
ο 
The doctor/genetic counselor 
encouraged me to share the 
information with blood 
relatives 
ο 
ο 
ο 
ο 
ο 
So my relatives could make 
family planning decisions 
ο 
ο 
ο 
ο 
ο 
To share the information I 
learned because I thought it 
was interesting 
ο 
ο 
ο 
ο 
ο 
To share my feelings about 
my genetic test results 
ο 
ο 
ο 
ο 
ο 
So I could get help from 
blood relatives with 
coordinating and planning for 
things like appointments and 
other health-related 
responsibilities (for example, 
going to doctors’ 
appointments, getting child 
care, getting transportation, 
etc.) 
ο 
ο 
ο 
ο 
ο 
 
19. Are there any other reasons that influenced your decision to share the results with blood 
relatives?  
 
 
20. (SKIP IF ANSWERED YES or I haven’t yet, but plan to TO QUESTION 16) On a scale of 
1 to 5, how important were each of the following reasons for not sharing your child’s genetic 
test results with blood relatives? 
 
Not at all 
important 
(1) 
2 
3 
4 
Very 
Important 
(5) 
I do not want to worry or 
upset them 
ο 
ο 
ο 
ο 
ο 
I would have to talk to a 
blood relative I’m not close 
to/prefer not to talk to 
ο 
ο 
ο 
ο 
ο 
I don’t have contact 
information for my blood 
relatives 
ο 
ο 
ο 
ο 
ο 

SouthSeq 4‐month post‐ROR Survey 
 
I have privacy concerns 
about sharing this 
information with my relatives 
ο 
ο 
ο 
ο 
ο 
I do not know how to explain 
the genetic results to my 
relatives 
ο 
ο 
ο 
ο 
ο 
I don’t think this information 
is useful for my relatives 
ο 
ο 
ο 
ο 
ο 
I’m having trouble coping 
with my child’s results 
ο 
ο 
ο 
ο 
ο 
I’m overwhelmed with my 
child’s medication condition 
ο 
ο 
ο 
ο 
ο 
I’m worried that my relatives 
will treat my child differently 
ο 
ο 
ο 
ο 
ο 
 
21. (SKIP IF ANSWERED YES OR I haven’t Yet but plan to, TO QUESTION 16) Are there 
any other reasons that influenced your decision not to share the results with blood relatives? 
 
 
 
22. What type of information did you share with blood relatives? Please check all that apply. 
 General information about the study results 
 Detailed information about the genes they tested 
 My relative’s risk of having a condition 
 Information about the possibility of being treated unfairly based on the study results 
 Recommendations of ways to prevent illness 
 Recommendations for more screening and testing 
 Feelings about the study results 
 Other, please specify:  
 
 
23. How did you share information about your child’s genetic test results with your blood 
relatives? Please check all that apply. 
 In person 
 By phone 
 By letter 
 By email 
 Through social Media 
 Other, please specify:  
 
 
 
24. Did you discuss your child’s genetic test results with your child’s doctor(s) or health care 
provider(s)? 
o Yes 
o Not yet, but I plan to 
o No and I don’t plan to (Skip to Question 26) 

SouthSeq 4‐month post‐ROR Survey 
 
25. If you answered yes to question 24. With whom did you discuss your child’s results? 
Please indicate which doctor(s) or health care provider(s) you shared results with. 
o Primary care doctor (pediatrician, family doctor) or nurse practitioner 
o NICU doctor or nurse practitioner 
o Neurologist 
o Another specialist  
 
26. If you answered “no and I don’t plan to”, why not?  
 
 
27. If you answered yes to question 26. Did your child’s doctor(s) or health care provider(s) 
make any recommendations based on the test result? 
o Yes 
o No 
o I don’t know / don’t remember 
 
28. If you answered yes to question 27. If yes, what were the recommendations (check all 
that apply)? 
a. Start a medicine 
b. Stop a medicine 
c. Change a medicine (change a dose of medicine) 
 
d. Start therapy (physical therapy, speech therapy, etc.) 
e. Stop therapy (physical therapy, speech therapy, etc.) 
f. 
Make changes to my child’s therapy (physical therapy, speech therapy, etc.) 
 
g. Order a medical test (x-ray, CAT scan, heart test, etc.) 
h. Cancel a medical test (x-ray, CAT scan, heart test, etc.) 
 
i. 
Refer my child to another healthcare provider 
j. 
Cancel a referral to a healthcare provider 
 
k. Change my child’s diet 
l. 
Start my child on vitamins or supplements 
 
29. If you checked j. What kind of healthcare provider(s) did your child’s doctor or nurse 
practitioner refer him/her to? (Check all that apply) 
a. Cardiologist (heart doctor) 
b. A neurologist (brain doctor) 
c. A geneticist (genetics doctor) 
d. A nephrologist (kidney doctor) 
e. A dermatologist (skin doctor) 
f. 
A pulmonologist (lung doctor) 
g. An immunologist (immune system doctor) 
h. A hematologist (blood doctor) 
i. 
An oncologist (cancer doctor) 
j. 
An audiologist (hearing doctor) 
k. A dentist 
l. 
A social worker 

SouthSeq 4‐month post‐ROR Survey 
 
m. A hospice or palliative care program 
n. Other  
 
 
30. Sometimes children qualify for clinical trials because they have received certain genetic test 
results. Was your child’s doctor able to find a clinical trial for your child? 
o Yes 
o No 
o I don’t remember 
o I don’t know 
31. If answered no to 30. Sometimes families find out their child doesn’t qualify for a certain 
clinical trial because they have received certain genetic test results. Did this happen to your 
child because of his/her genetic test results? 
o Yes 
o No 
o I don’t remember 
o I don’t know 
The last few questions have been asking you about what your child’s doctors or healthcare 
providers have recommended for your child. Now we want to know which of these things you’ve 
been able to do. 
32. The following options are only presented if they were selected in the previous 
question (question 28). Which of the following have you and your child been able to do so 
far as a result of your child’s genetic results? (check all that apply) 
a. Start a medicine 
b. Stop a medicine 
c. Change a medicine 
 
d. Start a kind of therapy (physical therapy, speech therapy, etc.) 
e. Stop a kind of therapy (physical therapy, speech therapy, etc.) 
f. 
Make changes to a therapy (physical therapy, speech therapy, etc.) 
 
g. Get a medical test (x-ray, CAT scan, heart test, etc.) 
h. Avoid getting a medical test (x-ray, CAT scan, heart test, etc.) 
 
i. 
See another healthcare provider 
j. 
Avoid having to see another healthcare provider 
 
k. Change my child’s diet 
l. 
Start my child on vitamins or another supplement 
 
33.  If you checked g. What kind of medical test(s) has your child had as a result of the genetic 
test results? (Check all that apply) 
a. Another genetic test 
b. Another type of blood test 
c. An X-ray 
d. An MRI 

SouthSeq 4‐month post‐ROR Survey 
 
e. A CAT scan 
f. 
A heart ultrasound or ECHO 
g. An ultrasound of another part of the body 
h. A test that required a surgery (such as a spinal tap or biopsy) 
i. 
Another kind of surgery (getting a g-tube or trach) 
j. 
A test of brain electricity (EEG) 
k. A test of heart electricity (EKG) 
l. 
A test of muscle electricity (EMG) 
m. A test of nerve electricity (nerve conduction test) 
n. Other  
 
 
34.  If you checked i. What kind of other healthcare provider(s) has your child seen as a result 
of his/her genetic test results? (Check all that apply) 
a. A cardiologist (heart doctor) 
b. A neurologist (brain doctor) 
c. A geneticist (genetics doctor) 
d. A nephrologist (kidney doctor) 
e. A dermatologist (skin doctor) 
f. 
A pulmonologist (lung doctor) 
g. An immunologist (immune system doctor) 
h. A hematologist (blood doctor) 
i. 
An oncologist (cancer doctor) 
j. 
An audiologist (hearing doctor) 
k. A dentist 
l. 
A social worker 
m. A hospice or palliative care program 
n. Other  
 
 
35. If at least one item was checked on 28, but no items were checked on 32. It looks like 
your child’s doctor or nurse practitioner recommended some things, but you haven’t been 
able to do those things. Why is that? 
 
 
36. If at least one item was checked on 28, but no items were checked on 32. Do you still 
plan on doing some of these things? 
o Yes 
o No 
 
37. If you responded “no” on 36. You said you don’t plan to do the things your child’s 
doctor(s) or health care provider(s) proposed. Why is that? 
 
 
38. Since you got your child’s genetic test results, have you been told by a doctor or other 
healthcare provider that your child’s diagnosis might affect future pregnancies in your 
family? 
o Yes 
o No 
o Not applicable (I wasn’t planning on having more kids) 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 8: DSMB Conflict of Interest Statement 

DNA Sequencing for Newborn Nurseries in the South 
(SouthSeq) 
Board Conflict of Interest and Confidentiality Statement 
Members of the Data and Safety Monitoring Board (DSMB) are selected to reflect the disciplines 
and medical specialties necessary to interpret data from the study(ies) named above. All 
members of the DSMB are required to be completely independent of the studies being reviewed 
and all members are required to sign a DSMB Conflict of Interest and Confidentiality statement. 
 
A conflict of interest exists when a DSMB member has a financial interest that could be affected 
by the study or a relationship with a study investigator that is likely to bias his or her review of it. 
An individual who has a financial conflict of interest with a study may not participate on its 
DSMB unless he or she receives a waiver from the NIH Institute or Center ethics official. 
Appearance of a conflict of interest should be avoided whenever possible; however, if it is 
established that there is no real conflict of interest and the ethics official determines that the 
integrity of the study would not be impaired, the individual in question may participate in the 
DSMB. Such actions by the ethics official shall be made in writing and become part of the 
DSMB record. 
 
It is the responsibility of each DSMB member to notify the NIEHS ethics official of any conflict 
of interest situations that may pertain, whether real or apparent. Conflict of interest can include 
personal, professional, financial or proprietary interest. Potential conflicts that develop during the 
member’s tenure on the DSMB must also be disclosed. Disclosure will serve to protect the 
integrity of the DSMB and its role in monitoring and oversight of clinical studies and will also 
help protect the DSMB member from allegations of inappropriate behavior. Failure to disclose a 
conflict of interest will lead to removal from the DSMB. The ethics official may independently 
determine that a particular situation involves a conflict of interest and consequently exclude the 
member from the DSMB. 
 
The following should be considered in assessing whether or not there is a conflict of interest. 
 
• 
Employment: Current or recent (within the past year) employment (e.g., full- or part- 
time salaried employee, consultant, or other recipient of honoraria; member of board of 
directors or advisory committee) with an institution or organization that is directly 
involved with conducting the research or that could receive financial benefit from the 
results of the study would generally be considered to be a conflict of interest. 
 
• 
Financial Benefit: An individual who has received or could receive direct financial 
benefit, other than from employment, of any amount from an individual, institution or 
organization involved with the study, other than the NIH, may have a conflict of interest. 
Financial benefit may include stock ownership or prior research funding from an 
institution or organization involved in the study, whose product is being evaluated in the 
study or competes with a product being evaluated in the study, or which could otherwise 

receive financial benefit from the results of the study. Regardless of the level of financial 
involvement, if the individual feels unable to provide objective advice, he/she must not 
serve on the DSMB. 
 
• 
Intellectual property: Intellectual property ownership, such as copyrights, patents, 
trademarks, trade names, or trade secrets related to the study may be considered a conflict 
of interest. 
 
• 
Relatives or Associates: A conflict of interest may exist if a close relative or 
professional associate of a member receives or could receive financial benefits from or 
provides financial benefits to the study or investigators. An apparent conflict of interest 
may also exist with a professional associate that includes any colleague, scientific 
mentor, or student with whom the DSMB member is currently conducting research or 
other professional activities or with whom the DSMB member has personally worked or 
published with within three years. 
 
• 
Longstanding Disagreements: A conflict of interest may exist when a DSMB member 
has had longstanding scientific or personal differences with the study or its investigator(s) 
that may compromise objectivity. 

Confidentiality and Non-Disclosure of Materials and Proceedings 
Materials and information made available to the DSMB that are not in the public domain, as well 
as the discussions that take place during the meetings, are strictly confidential and must not be 
disclosed to or discussed with anyone who is not a member of the DSMB. Furthermore, 
confidential information obtained as a DSMB member may not be used by the member for 
personal benefit or for the benefit of the member’s family, associates, or of organizations with 
which the individual is associated or has a financial involvement. 
 
DSMB Certification Regarding Conflict of Interest, Confidentiality, and Non- 
Disclosure 
NAME:  
 
 
Primary employer:  
 
 
[ ] I have read the attached DSMB Conflict of Interest and Confidentiality Form and hereby 
certify that I do not have a conflict of interest or have discussed and resolved with the ethics 
official any potential conflict of interest with the study reviewed by this DSMB. 
 
[ ] I fully understand the confidential nature of the DSMB process and agree not to disclose or 
discuss the materials associated with the review or substance of any confidential discussions 
about the studies with any individual not a member of the DSMB or to use the information for 
my personal benefit or the benefit of others. 
 
 
 
Signature:  
 
 
 
 
Date:  
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 9: DSMB Plan and Charter 

Data and Safety Monitoring Board (DSMB) Charter 
 
This DSMB has been convened as a method for additional monitoring of study procedures. The safety of 
the study participants is the highest priority for this project. The ability to make appropriate, sound 
scientific decisions regarding the outcome of each participant, as early as possible, is the top priority. 
The DSMB will be comprised of three scientists/clinicians who are independent of the study. 
DSMB Responsibilities 
• 
Review the outcome instruments, informed consent documents and plans for data safety and 
monitoring 
• 
Evaluate the progress of the clinical trial, including periodic assessments of data quality and 
timeliness, recruitment, accrual and retention, participant risk versus benefit, and other factors 
that can affect study outcome 
• 
Consider factors external to the study when relevant information becomes available, such as 
scientific or therapeutic developments that may have an impact on the safety of the participants 
or the ethics of the trial 
• 
Review study performance, make recommendations and assist in the resolution of problems 
reported by the Principal Investigator(s) (Clinical Trial PIs) 
• 
Protect the safety of the study participants and monitor the rate and scope of errors reported in 
the experimental arm of the clinical trial. 
• 
Report on the safety and progress of the trial 
• 
Make recommendations to the PIs concerning continuation, termination or other modifications 
of the trial based on the observed beneficial or adverse effects of the intervention under study 
• 
The PIs will report findings of the DSMB to NGHRI in accordance with reporting guidelines 
• 
Ensure the confidentiality of the study data and the results of monitoring 
• 
Assist in commenting on any problems with study conduct, enrollment, sample size, and/or data 
collection. 
The DSMB will discharge itself from its duties when the last participant completes the clinical trial. 
 
DSMB Board Process 
At the initial meeting the DSMB will discuss the protocol, suggest modifications, and establish guidelines 
to study monitoring by the Board. The DSMB Chairperson, in consultation with the Principal Investigator 
and the study team, will prepare the agenda to address the review of provider education materials, 
modifications to the study protocol and informed consent document, initiation of the trial, reporting of 
return of results errors, and statistical analysis plan. Meetings of the DSMB will be held annually or 
more frequently at the discretion of the DSMB, if necessary. The study investigators or their designees 
will attend the meetings. An emergency meeting of the DSMB may be called at any time by the 
Chairperson or by the PIs should safety questions or other unanticipated problems arise. The meetings 
are closed to the public because discussions may address confidential participant data. The meetings are 
attended by the Principal Investigators and members of their staff. Meetings may be convened as 
conference calls, as well as in-person. 
 
DSMB Meeting Format 
DSMB meetings will consist of open and closed sessions. Discussion held in all sessions is confidential. 
The PI and key members of the study team attend the open sessions. Discussion will focus on the 

conduct and progress of the study, including participant accrual, protocol compliance, and problems 
encountered. 
 
Each meeting must include a recommendation to continue or to terminate the study and whether the 
DSMB has any concerns about participant safety made by a formal DSMB majority or unanimous vote. 
Should the DSMB decide to issue a termination recommendation, the full vote of the DSMB is required. 
In the event of a split vote, majority vote will rule and a minority report will be appended. The DSMB 
Chair provides the tiebreaking vote in the event of a 50-50 split vote. A recommendation to terminate 
the study may be made by the DSMB at any time by majority vote. The Chair should provide such a 
recommendation to the PIs immediately by telephone and email. 
 
Meeting Materials 
A DSMB interim report template will be prepared by the study staff, typically by the study statistician, 
and will be reviewed by the DSMB members at the first meeting. The format and the content of the 
reports for, and the plans for, interim analyses will be finalized and approved at the initial DSMB 
meeting, although changes throughout the trial may be requested by the Board. The reports will list and 
summarize safety data and describe the status of the study. All meeting materials will be sent to PIs who 
will forward the materials to the DSMB between 7 to 14 days prior to the meeting. The reports will be 
numbered and provided in sealed envelopes and can be returned within an express mailing package or 
by secure email, as the DSMB prefers. In select cases, PIs may approve direct mailing of the reports from 
the study to the DSMB. 
 
DSMB Reports 
Reports generally include administrative reports by site that describe participants screened, enrolled, 
completed, and discontinued, as well as baseline characteristics of the study population, and interim 
error statistics from HudsonAlpha obtained through review of the ROR sessions (i.e. errors tracking). 
Other general information on study status may also be presented. The DSMB may direct additions and 
other modifications to the reports on a one-time or continuing basis. The reports may also contain data 
on study outcomes, including safety data, and perhaps efficacy data. 
A formal report containing the recommendations for continuation of, or modification to the study will 
be prepared by the DSMB Chairperson, PIs, or designee. The draft report will be sent to the DSMB 
members for review and approval. It is the responsibility of the PIs to distribute the DSMB 
recommendation to all co-investigators and to ensure that copies are submitted to the IRBs. As 
previously stated, the formal DSMB report must include a recommendation to continue or to terminate 
the study. This recommendation should be made by formal majority vote. A termination 
recommendation may be made by the DSMB at any time by majority vote. In the event of a split vote in 
favor of continuation, a minority report will be contained within the regular DSMB report. 
 
DSMB Confidentiality 
All materials, discussions and proceedings of the DSMB are completely confidential. Members and other 
participants in DSMB meetings are expected to maintain confidentiality. 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 10: Training Log 

Training Log 
 
Sponsor: 
NHGRI 
Protocol: 
DNA Sequencing for Newborn Nurseries in the South 
(SouthSeq) 
Site/PI Name: 
Training Date: 
Trainer/Affiliation 
Subject: 
 
Meeting Participants 
 
Name 
Signature 
Study Role/Responsibility 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 11: Screening Log 

 
Study: SouthSeq 
Principal Investigators: Bruce Korf, MD, PhD (University of Alabama at Birmingham); Greg Cooper, PhD (HudsonAlpha); Greg Barsh, MD (HudsonAlpha) 
Procedure: Whole Genome Sequencing (WGS) 
Protocol Version: TBN 
Target Goal: 800 families with proband sequenced 
 
 
 
Screening ID 
Proband Demographics 
Date of Consent 
MM/DD/YYYY 
SouthSeq ID 
Eligible for Enrollment 
(Yes/No) 
If not enrolled, provide a 
reason 
If other, describe 
Eligible but declined 
Gender Ethnicity 
Race Date of Screening 
Completed decliner survey 
(Yes/No) 
Enrolled in Clinical Trial 
Yes/No 
Completed W9 
Yes/No 
Genome 
Gateway Account 
Created? 
(Yes/No) 
Consent 
version 
(Approval 
Date) 
Awaiting 
RoR 
Additional 
Notes 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 12: Communication Log 

Communication Log 
 
Sponsor: 
NHGRI 
Protocol: 
DNA Sequencing for Newborn Nurseries in the South 
(SouthSeq) 
Site/PI Name: 
 
Calls/Meetings 
 
Name 
Recipient 
Subject 
Notes 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 13: Return of Results (ROR) Audio Recording 

Audio Recording Process in SouthSeq 
Audio recorder supplies: 
• Recorder, something like https://www.amazon.com/Sony-ICDPX370-Digital-Recorder- 
Built/dp/B06XFTWCBJ/ref=sr_1_4?ie=UTF8&qid=1547149909&sr=8- 
4&keywords=digital+recorder+built+in+usb 
• Phone adapter 
https://www.amazon.com/gp/product/B000KL0XA6/ref=oh_aui_detailpage_o08_s00?ie 
=UTF8&psc=1 
• Batteries 
 
Protocol: 
1. Make sure recorder is charged/has power (prior to result appointment) 
2. At beginning of RoR session, prior to starting recording, say the following: 
 
“I want to remind you that as part of the SouthSeq study, we are audio-recording 
conversations about test results. The reason we are recording our meeting today is so that 
study researchers can learn more about how healthcare providers talk about genetics and 
describe test results. Only the study team will have access to the recording. Is it OK that I 
turn on the audio recorder now?” 
 
If yes  Turn on audio recorder and proceed with #5 
If no  Read this fallback text: 
 
“The study requests recording of the conversations when participants receive results. The 
reason for this request is that is important for the study to learn from our experiences and 
how we describe results to you. Is there anything else I can explain to make you more 
comfortable about it?” 
If yes  Answer questions and ask again for permission to turn on audio recorder 
If no  Is the participant in the standard of care arm (randomized to disclosure by genetics 
provider)? 
If yes (disclosure by genetics provider)  Proceed with #3 
If no (disclosure by non-genetics provider)  Proceed with #4 
3. The participant can opt-out of audio recording and still receive results at the current 
time. Put away the audio recorder and proceed with the disclosure of results. Following 
the disclosure, message the HudsonAlpha genetic counselor assigned to your site* to 
say that the participant (give study ID#) declined audio recording. Do not proceed with 
any further steps. 

4. The participant can opt-out of audio recording but unfortunately cannot receive results 
from a non-genetics provider without audio recording permission. Tell the family: 
“Unfortunately, because of our research plan and for your safety, I cannot discuss the 
results with you right now without using audio recording. If you choose to opt out of 
having this conversation recorded, we can have a genetic counselor for the study discuss 
the results with you at another time. Is that what you would like to do?” 
 
If yes  Apologize for the inconvenience, tell them a study genetic counselor will be in 
touch soon, and that the results will be placed into the child’s medical record once the 
results have been discussed with the family. Notify the study coordinator at the site* and 
the HudsonAlpha genetic counselor assigned to your site of status. 
If no (would like to proceed with audio recording)  Proceed to step 5 
 
5. State the proband’s study ID# clearly on the recording, along with the date and the 
name of the provider doing the result return. 
6. Disclose the results to the participant family. Elicit and answer questions from the 
family. 
 
7. Once the result disclosure conversation is concluded, end the recording. 
 
8. Give audio recorder back to site coordinator/research nurse. 
9. Study Coordinator: Save the audio file to a secure, HIPAA compliant computer or 
storage drive using the study ID number as the file name, and upload the file within 
Genome Gateway to the HudsonAlpha genetic counselor assigned to your particular 
site.* This is done by selecting files on the left side menu, clicking on the person you 
want to send the file to from the list of people, and then clicking the “add file” button in 
the top right corner of the screen. This will allow you to select a file from your computer 
to send. 
10. Study Coordinator: Maintain an electronic, backup copy of all audio files on a computer 
prior to deleting the files from the recording device. 
 
11. HudsonAlpha genetic counselors: review the audio recording for disclosures in the 
experimental arm of the trial (disclosure by non-genetics provider). This review will 
occur within a week for negative results, within 72 business hours for positive and 
uncertain results and any errors will be tracked (minor errors, major errors, safety 
errors). All errors will be tracked for future aggregate analysis. Only major/safety errors 
will trigger real-time feedback to the disclosing provider from the genetic counselor. 
Store all audio files in a centralized, electronic location that is HIPAA compliant, 
organized by site, randomization arm, and study ID. 

*HudsonAlpha Genetic Counselor contacts by site: 
Alabama: Meagan Cochran 
Mississippi: Whitley Kelley 
Louisiana: Veronica Greve 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 14: Certified Letter Template 

 
 
 
 
 
[Date] 
 
Guardian of [Patient Name] 
 
Patient: [Patient Name] 
Date of Birth: [Patient DOB] 
Dear family of [Patient Name]: 
 
Multiple attempts to reach you via phone have been unsuccessful. See enclosed your child’s 
results from the SouthSeq research study that you enrolled in on [Enrollment Date]. Upon 
review of these results, please call [Provider Name], [Recruitment Site, Provider Title] for 
SouthSeq at [Provider Phone Number]. Thank you. 
Sincerely, 
 
 
[Provider Name] 
[Provider Title] 

1 
 
 
 
 
 
 
 
Appendix 15: 
Return of Results Workflow 

2 
 
SouthSeq Result Return Workflow 
for Site Coordinators 
Return of Results for Cases randomized to Standard of Care Arm (GC disclosure) 
Preparation 
1. Receive message within Genome Gateway from HA genetic counselor that a case has 
results ready to be returned and has been randomized to GC disclosure. Message will 
include participant ID. Site GC will also receive this message. 
2. Review result report, attached to the message sent in Genome Gateway. Reach out to 
HA genetic counselor with any questions or concerns. 
3. Return of result visit gets scheduled with primary parent contact. Depending on site- 
specific procedures this could be done by the GC, site coordinator, or administrative 
support. Encourage in-person disclosure if possible. At this time, confirm that the 
participant’s address has not changed. If it has, please update it in the demographics 
section of Genome Gateway and have them complete a new W9 form. The new W9 
should be uploaded to the participants account and to the “Clinical Trial” account in 
Genome Gateway. 
Disclosure (via phone) 
1. Site genetic counselor will call the primary parent contact at the scheduled time. 
2. RESULTS ARE DISCLOSED by the site genetic counselor. 
3. Site genetic counselor will be in communication with you during the disclosure to let you 
know if they successfully connected with the family and when the conversation is 
finished. 
4. Once result disclosure is in process, log into Genome Gateway and assign the “In-clinic 
Survey” and “At-Home Survey” to the participant. 
5. Site genetic counselor will transfer the call to you when disclosure is over, if you are 
available. If you are not available at that time, call the primary parent contact back 
within the next 72 hours. Attempt to reach multiple times if no answer. 
6. Over the phone, have primary parent contact complete the “In-clinic survey” by asking 
the questions and marking their response on a paper version of the survey. The paper 
survey should then be scanned and uploaded to the participant’s account and to the 
Clinical Trial account. If the participants decide not to do the survey over the phone, 
please remind them to log into Genome Gateway to complete them and remind them 
that compensation will be provided for completed surveys. 
7. Discuss next steps in SouthSeq for family to expect (see below “Next Steps” list). 
8. Find out if they remember their Genome Gateway username/password and website? If 
not, give it to them. If they don’t remember their password there is a link on the GG 
website they can click to re-set. (participants.southseq.org) 
Disclosure (in-person) 
1. RESULTS ARE DISCLOSED by the site genetic counselor. 

3 
 
2. Site genetic counselor will be in communication with you to let you know if the family 
showed up and when the conversation is finished. 
3. Once result disclosure is in process, log into Genome Gateway and assign the “In-Clinic 
Survey” and “At-Home Survey” to the participant. 
4. Site genetic counselor will let you know when the result disclosure is finished and the 
family is ready to complete the in-clinic survey. 
5. Go into room with study iPad and have family log into their Genome Gateway account 
(participants.southseq.org). If they do not remember their password there is a link on 
the website to re-set it via email. 
a. If participants cannot get into their email to reset a forgotten password, you can 
contact your HA genetic counselor to have it manually reset. 
b. If technology fails completely, have a paper version of the surveys available as a 
last resort. However, it is critical to get families into Genome Gateway and 
familiar with it to increase future questionnaire completion. 
6. Discuss next steps in SouthSeq for family to expect (see attached “Next Steps” list). 
 
Follow-up 
1. Site genetic counselor is responsible for completing “Result Return” provider survey, 
uploading audio file, and mailing copies of results for phone disclosures. 
2. Ensure copy of result report gets in the patient’s medical record. 
Return Results for Cases randomized to Experimental Arm (NICU disclosure) 
Preparation 
1. Receive message within Genome Gateway from HA genetic counselor that a case has 
results ready to be returned and has been randomized to NICU non-genetic professional 
disclosure. Message will include participant ID. 
2. Review result report, attached to the message sent in Genome Gateway. Reach out to 
HA genetic counselor with any questions or concerns. 
3. Return of result visit gets scheduled with primary parent contact. Depending on site 
specific procedures this could be done by the GC, site coordinator, or administrative 
support. Encourage in-person disclosure if possible. At this time, confirm that the 
participant’s address has not changed. If it has, please update it in the demographics 
section of Genome Gateway and have them complete a new W9 form. The new W9 
should be uploaded to the participants account and to the “Clinical Trial” account in 
Genome Gateway. 
4. Within NICU determine which provider will be doing the disclosure. Communicate this 
name to your HA genetic counselor when it is known. (This process will be site specific, 
once you have an established process, please send a description of that process to 
Candice Finnila.) 
 
Disclosure (via phone) 
9. Disclosing NICU provider will call the primary parent contact at the scheduled time. 
10. RESULTS ARE DISCLOSED by the NICU provider. 

4 
 
11. NICU provider will be in communication with you to let you know if they successfully 
connected with the family and when the conversation is finished. 
12. Once result disclosure is in process, log into Genome Gateway and assign the “In-clinic 
Survey” and “At-Home Survey” to the participant. 
13. NICU provider will transfer the call to you when disclosure is over, if you are available. If 
you are not available at that time, call the primary parent contact back within the next 
72 hours. Attempt to reach multiple times if no answer. 
14. Over the phone, have primary parent contact complete the “In-clinic survey” by asking 
the questions and marking their response on a paper version of the survey. 
15. Discuss next steps in SouthSeq for family to expect (see below “Next Steps” list). 
16. Find out if they remember their Genome Gateway username/password and website? If 
not, give it to them. If they don’t remember their password there is a link on the GG 
website they can click to re-set. (participants.southseq.org) 
Disclosure (in-person) 
7. Make sure disclosing provider has audio recording equipment (recorder with 
charge/batteries/available storage). 
8. Make sure disclosing provider has a printed copy of the report to give to the family. 
9. RESULTS ARE DISCLOSED by the NICU provider. 
10. NICU provider will be in communication with you during the disclosure to let you know 
if the family showed up and when the conversation is finished. 
11. Once result disclosure is in process, log into Genome Gateway and assign the “In-Clinic 
Survey” and “At-Home Survey” to the participant. 
12. NICU provider will let you know when the result disclosure is finished and the family is 
ready to complete the in-clinic survey. 
13. Go into room with study iPad and have family log into their Genome Gateway account 
(participants.southseq.org). If they do not remember their password there is a link on 
the website to re-set it via email. 
a. If participants cannot get into their email to reset a forgotten password, you can 
contact your HA genetic counselor to have it manually reset. 
b. If technology fails completely, have a paper version of the surveys available as a 
last resort. However, it is critical to get families into Genome Gateway and 
familiar with it to increase future questionnaire completion. 
14. Discuss next steps in SouthSeq for family to expect (see attached “Next Steps” list). 
Follow-up 
1. Get audio recorder back from NICU provider. 
2. Upload audio recording to computer. Keep copy stored locally on computer. Send file to 
HA genetic counselor in Genome Gateway. Do NOT upload recording to participant’s 
account, should be uploaded directly to the HA genetic counselor. 
3. (If result return was done by phone) Mail hard copy of result letter to participant. 
4. Ensure copy of result report gets in the patient’s medical record. 
Certified Letters (if needed) 

5 
 
1. Certified letter disclosure should be triggered if you cannot reach family after 2 
attempts to primary phone plus one attempt at non-household contact 
2. Alert site genetic counselor when a case reaches this threshold and a certified letter 
should be sent. 
3. Certified letters will be sent by the site genetic counselor. 
Re-analysis/Amended Reports (if new information leads to change in result) 
1. Receive a message from HA GC that an amended report is available, amended report 
will be uploaded in Genome Gateway. 
2. Review result report, attached to the message sent in Genome Gateway. Reach out to 
HA genetic counselor with any questions or concerns. 
3. Amended result will be returned by same type of provider (same study arm) that 
returned the initial result (genetic counselor or NICU provider). Does not have to be the 
same exact provider. 
4. For NICU provider disclosures, determine which provider will be doing the disclosure. 
Communicate this name to your HA genetic counselor when it is known via Genome 
Gateway. 
5. Amended result is communicated by appropriate provider (likely by phone, but any 
mode of communication is fine). Utilize audio recorder as described elsewhere. 
6. Follow-up the same as for initial disclosure (audio recordings sent to HA, copy of results 
mailed to participant, copy of results into EMR, update the child’s clinical team, if 
possible). 
Next Steps (what participants can expect): 
 Surveys: 
o Encourage survey completion! 
o There is financial compensation for completion of surveys ($25/completed 
survey). 
o There are two brief surveys we will ask you to do on Genome Gateway right 
away after our conversation. 
o At several points over the next several months there will be new surveys to 
complete in Genome Gateway (family will receive message/email/text when it is 
time). 
 Result Report: 
o A copy of the result report will be available to view/download in Genome 
Gateway within next couple of days. 
o A paper copy will also be mailed (if phone disclosure). 
o A copy will also be put in child’s medical record. 
 Education: 
o Some additional educational information about genetics and the result will be 
available in Genome Gateway a couple of days post-RoR (family will receive a 
message/email/text when they are available). 
o Educational materials can be accessed at any time in the future using Genome 
Gateway. 

6 
 
 Clinical Follow-up: 
o If in-patient disclosing provider will discuss result with [relevant doc] and they 
will make decisions about management. If out-patient, encourage patient to do 
whatever is needed to get looped into genetics. 
o Encourage patients to take copies of results reports to future appointments. 

7 
 
Audio Recording Protocol in SouthSeq 
1. Make sure recorder is charged/has power (prior to result appointment) 
 
2. At beginning of RoR session, prior to starting recording, say the following: 
 
“I want to remind you that as part of the SouthSeq study, we are audio-recording 
conversations about test results. The reason we are recording our meeting today is so that 
study researchers can learn more about how healthcare providers talk about genetics and 
describe test results. Only the study team will have access to the recording. Is it OK that I 
turn on the audio recorder now?” 
 
If yes  Turn on audio recorder and proceed with #5 
If no  Read this fallback text: 
“The study requests recording of the conversations when participants receive results. The 
reason for this request is that is important for the study to learn from our experiences and 
how we describe results to you. Is there anything else I can explain to make you more 
comfortable about it?” 
If yes  Answer questions and ask again for permission to turn on audio recorder 
If no  Is the participant in the standard of care arm (randomized to disclosure by genetics 
provider)? 
If yes (disclosure by genetics provider)  Proceed with #3 
If no (disclosure by non-genetics provider)  Proceed with #4 
 
3. The participant can opt-out of audio recording and still receive results at the current 
time. Put away the audio recorder and proceed with the disclosure of results. 
Following the disclosure, message the HudsonAlpha genetic counselor assigned to 
your site* to say that the participant (give study ID#) declined audio recording. Do 
not proceed with any further steps. 
 
4. The participant can opt-out of audio recording but unfortunately cannot receive 
results from a non-genetics provider without audio recording permission. Tell the 
family: 
 
“Unfortunately, because of our research plan and for your safety, I cannot discuss 
the results with you right now without using audio recording. If you choose to opt 
out of having this conversation recorded, we can have a genetic counselor for the 
study discuss the results with you at another time. Is that what you would like to 
do?” 

8 
 
If yes  Apologize for the inconvenience, tell them a study genetic counselor will be in 
touch soon, and that the results will be placed into the child’s medical record once the 
results have been discussed with the family. Notify the study coordinator at the site* 
and the HudsonAlpha genetic counselor assigned to your site of status. 
If no (would like to proceed with audio recording)  Proceed to step 5 
 
5. State the proband’s study ID# clearly on the recording, along with the date and the 
name of the provider doing the result return. 
 
6. Disclose the results to the participant family. Elicit and answer questions from the 
family. 
 
7. Once the result disclosure conversation is concluded, end the recording. 
8. Give audio recorder back to site coordinator/research nurse. 
 
9. Study Coordinator: Save the audio file to a secure, HIPAA compliant computer or 
storage drive using the study ID number as the file name, and upload the file within 
Genome Gateway to the HudsonAlpha genetic counselor assigned to your particular 
site.* This is done by selecting files on the left side menu, clicking on the person you 
want to send the file to from the list of people, and then clicking the “add file” button 
in the top right corner of the screen. This will allow you to select a file from your 
computer to send. 
 
10. Study Coordinator: Maintain an electronic, backup copy of all audio files on a 
computer prior to deleting the files from the recording device. 
 
11. HudsonAlpha genetic counselors: review the audio recording for disclosures in the 
experimental arm of the trial (disclosure by non-genetics provider). This review will 
occur within a week for negative results, within 72 business hours for positive and 
uncertain results and any errors will be tracked (minor errors, major errors, safety 
errors). All errors will be tracked for future aggregate analysis. Only major/safety 
errors will trigger real-time feedback to the disclosing provider from the genetic 
counselor. Store all audio files in a centralized, electronic location that is HIPAA 
compliant, organized by site, randomization arm, and study ID. 
 
*HudsonAlpha Genetic Counselor contacts by site: 
Alabama: Meagan Cochran 
Mississippi: Whitley Kelley 
Louisiana: Veronica Greve 

1 
 
SouthSeq Result Return Workflow 
for Site Genetic Counselors 
Variant Review for Cases with WGS findings 
1. Receive notification via email that a case has findings and is ready for review in 
Freedcamp (SouthSeq-VRC Reports) 
2. Review case/findings in Freedcamp and provide comments as appropriate (within 24-48 
business hours) 
Return Results for Cases randomized to Clinical Trial Standard of Care Arm 
Preparation 
1. Receive message within Genome Gateway from HA genetic counselor that a case has 
results ready to be returned (and has been randomized to GC disclosure). Message will 
include participant ID. 
2. Review result report, attached to the message sent in Genome Gateway. Reach out to 
HA genetic counselor with any questions or concerns. 
3. Return of result visit gets scheduled with primary parent contact. Depending on site 
specific procedures this could be done by the GC or by administrative support. 
Encourage in-person disclosure if possible. 
Disclosure (via phone) 
1. Connect recording equipment to phone (phone adapter and recorder). 
2. At the scheduled time, call the primary parent contact. Confirm it is a good time to 
discuss SouthSeq results. Document who (all) is on the phone listening and their 
relationship to proband. 
3. Read script from recording procedure and obtain permission to turn on recorder (see 
attached “Audio Recording Protocol”). 
4. Turn on recorder and state on the recording the participant study ID#. 
5. DISCLOSE RESULTS TO FAMILY. Answer questions specific to result disclosure discussion, 
being careful not to extend discussion into initiating additional care management plans 
(management examples may still be discussed, just not initiated during this encounter). 
6. Discuss next steps in SouthSeq for family to expect (see below “Next Steps” list). 
7. Find out if they remember their Genome Gateway username/password and website? If 
not, give it to them. If they don’t remember their password there is a link on the GG 
website they can click to re-set. (participants.southseq.org) 
8. Wrap up conversation. End Recording. 
9. Notify site study coordinator disclosure is finished, transfer call to study coordinator if 
available for post result surveys. 
Disclosure (in-person) 
1. Make sure recording equipment is available and ready. 
2. Have printed copy of result report to give to family. 
3. Document who (all) attends disclosure and their relationship to proband. 

2 
 
4. Read script from recording procedure and obtain permission to turn on recorder (see 
attached “Audio Recording Protocol”). 
5. Turn on recorder and state on the recording the participant study ID#. 
6. DISCLOSE RESULTS TO FAMILY. Answer questions specific to result disclosure discussion, 
being careful not to extend discussion into initiating additional care management plans 
(management examples may still be discussed, just not initiated during this visit). 
7. Discuss next steps in SouthSeq for family to expect (see attached “Next Steps” list). 
8. Find out if they remember their Genome Gateway username/password and website? If 
not, give it to them. If they don’t remember their password there is a link on the GG 
website they can click to re-set. (participants.southseq.org) 
9. Wrap up disclosure. End Recording. 
10. Notify site study coordinator disclosure is finished, study coordinator will come into the 
room to facilitate post result surveys. 
 
Certified Letters (if needed) 
1. Certified letter disclosure should be triggered if you cannot reach family after 2 
attempts to primary phone plus one attempt at non-household contact. 
2. Use certified mail to send result letter and SouthSeq cover letter. Depending on the site, 
this task could be done by the site coordinator or administrative support. 
3. Complete “Result Return” questionnaire at time letter is sent. 
4. If contact is made with the family, or if the letter is returned undeliverable, add this 
information to the “Result Return” survey (in the open text box) and submit it again. 
5. Send HudsonAlpha GC message in Gateway to inform of that an update has been made. 
 
Follow-up 
1. Complete “Result Return” questionnaire in Genome Gateway (assigned to you by HA 
genetic counselor). 
2. Upload audio recording to computer. Keep copy stored locally on computer. Send file to 
HA genetic counselor in Genome Gateway. Do NOT upload recording to participant’s 
account, should be uploaded directly to the HA genetic counselor. 
3.  (If result return was done by phone) Mail hard copy of result letter to participant. 
Remember do not include any additional letters/notes/information. 
4. Document results/disclosure clinically at institution. Pass result off to clinical team. 
Re-analysis/Amended Reports (if new information leads to change in result) 
1. Receive a message from HA GC that an amended report is available, amended report 
will be uploaded in Genome Gateway. 
2. Contact the patient with the new information (likely by phone, but any mode of 
communication is fine). Utilize audio recorder as described elsewhere. 
3. Complete “Amended Result Return” questionnaire in Genome Gateway (assigned to you 
by HA genetic counselor). 
4. Upload audio recording to computer. Keep copy stored locally on computer. Send file to 
HA genetic counselor in Genome Gateway. Do NOT upload recording under participant’s 

3 
 
account, label the audio file using the SouthSeq study ID instead and upload it to the HA 
GC only. 
5. (If RoR by phone) Mail hard copy of result letter to participant. Remember do not 
include any additional letters/notes/information. 
6. Document results/disclosure clinically at institution. Pass result off to clinical team. 
Next Steps (what participants can expect): 
 Surveys: 
o Encourage survey completion! 
o There is financial compensation for completion of surveys ($25/completed 
survey). 
o There are two brief surveys we will ask you to do on Genome Gateway right 
away after our conversation. 
o At several points over the next several months there will be new surveys to 
complete in Genome Gateway (family will receive message/email/text when it is 
time). 
 Result Report: 
o A copy of the result report will be available to view/download in Genome 
Gateway within next couple of days. 
o A paper copy will also be mailed (if phone disclosure). 
o A copy will also be put in child’s medical record. 
 Education: 
o Some additional educational information about genetics and the result will be 
available in Genome Gateway a couple of days post-RoR (family will receive a 
message/email/text when they are available). 
o Educational materials can be accessed at any time in the future using Genome 
Gateway. 
 Clinical Follow-up: 
o If in-patient still can say that you will discuss result with [relevant doc] and they 
will make decisions about management. If out-patient, encourage patient to do 
whatever is needed to get looped into genetics. Avoid doing clinical care during 
the research result disclosure. 
o Regardless, encourage patients to take copies of results reports to future 
appointments. 

4 
 
Audio Recording Protocol in SouthSeq 
1. Make sure recorder is charged/has power (prior to result appointment) 
 
2. At beginning of RoR session, prior to starting recording, say the following: 
 
“I want to remind you that as part of the SouthSeq study, we are audio-recording 
conversations about test results. The reason we are recording our meeting today is so that 
study researchers can learn more about how healthcare providers talk about genetics and 
describe test results. Only the study team will have access to the recording. Is it OK that I 
turn on the audio recorder now?” 
 
If yes  Turn on audio recorder and proceed with #5 
If no  Read this fallback text: 
“The study requests recording of the conversations when participants receive results. The 
reason for this request is that is important for the study to learn from our experiences and 
how we describe results to you. Is there anything else I can explain to make you more 
comfortable about it?” 
If yes  Answer questions and ask again for permission to turn on audio recorder 
If no  Is the participant in the standard of care arm (randomized to disclosure by genetics 
provider)? 
If yes (disclosure by genetics provider)  Proceed with #3 
If no (disclosure by non-genetics provider)  Proceed with #4 
 
3. The participant can opt-out of audio recording and still receive results at the current 
time. Put away the audio recorder and proceed with the disclosure of results. 
Following the disclosure, message the HudsonAlpha genetic counselor assigned to 
your site* to say that the participant (give study ID#) declined audio recording. Do 
not proceed with any further steps. 
 
4. The participant can opt-out of audio recording but unfortunately cannot receive 
results from a non-genetics provider without audio recording permission. Tell the 
family: 
 
“Unfortunately, because of our research plan and for your safety, I cannot discuss 
the results with you right now without using audio recording. If you choose to opt 
out of having this conversation recorded, we can have a genetic counselor for the 
study discuss the results with you at another time. Is that what you would like to 
do?” 

5 
 
If yes  Apologize for the inconvenience, tell them a study genetic counselor will be in 
touch soon, and that the results will be placed into the child’s medical record once the 
results have been discussed with the family. Notify the study coordinator at the site* 
and the HudsonAlpha genetic counselor assigned to your site of status. 
If no (would like to proceed with audio recording)  Proceed to step 5 
 
5. State the proband’s study ID# clearly on the recording, along with the date and the 
name of the provider doing the result return. 
 
6. Disclose the results to the participant family. Elicit and answer questions from the 
family. 
 
7. Once the result disclosure conversation is concluded, end the recording. 
8. Give audio recorder back to site coordinator/research nurse. 
 
9. Study Coordinator: Save the audio file to a secure, HIPAA compliant computer or 
storage drive using the study ID number as the file name, and upload the file within 
Genome Gateway to the HudsonAlpha genetic counselor assigned to your particular 
site.* This is done by selecting files on the left side menu, clicking on the person you 
want to send the file to from the list of people, and then clicking the “add file” button 
in the top right corner of the screen. This will allow you to select a file from your 
computer to send. 
 
10. Study Coordinator: Maintain an electronic, backup copy of all audio files on a 
computer prior to deleting the files from the recording device. 
 
11. HudsonAlpha genetic counselors: review the audio recording for disclosures in the 
experimental arm of the trial (disclosure by non-genetics provider). This review will 
occur within a week for negative results, within 72 business hours for positive and 
uncertain results and any errors will be tracked (minor errors, major errors, safety 
errors). All errors will be tracked for future aggregate analysis. Only major/safety 
errors will trigger real-time feedback to the disclosing provider from the genetic 
counselor. Store all audio files in a centralized, electronic location that is HIPAA 
compliant, organized by site, randomization arm, and study ID. 
 
*HudsonAlpha Genetic Counselor contacts by site: 
Alabama: Meagan Cochran 
Mississippi: Whitley Kelley 
Louisiana: Veronica Greve 

1 
 
SouthSeq Result Return Workflow 
for Site NICU Providers (non-genetic providers) 
Variant Review for Cases with WGS findings 
1. Receive notification via email that a case has findings and is ready for review in 
Freedcamp (SouthSeq-VRC Reports) 
2. Review case/findings in Freedcamp and provide comments as appropriate (within 24-48 
business hours) 
Return Results for Cases randomized to Clinical Trial Experimental Arm 
Preparation 
1. Your SouthSeq site coordinator will receive a message within Genome Gateway from 
the HA genetic counselor that a case has results ready to be returned by a NICU 
provider. The result report will be uploaded in Genome Gateway to the coordinator. 
2. Within NICU team it will be decided which NICU provider will do disclosure. Care should 
be taken to avoid having provider currently doing care of child do disclosure if possible. 
3. Site coordinator will send you a copy of any result reports that you will be responsible 
for disclosing. This will be sent as a file in Genome Gateway. 
4. Review result report. Reach out to HA genetic counselor* (via Genome Gateway) with 
any questions or concerns. 
5. Site coordinator will work with you to schedule return of result visit with primary parent 
contact. Encourage in-person disclosure if possible. 
Disclosure (via phone) 
1. Connect recording equipment to phone (phone adapter and recorder). 
2. At the scheduled time, call the primary parent contact. Confirm it is a good time to 
discuss SouthSeq results. Document who (all) is on the phone listening and their 
relationship to proband. 
3. Read script from recording procedure and obtain permission to turn on recorder (see 
attached “Audio Recording Protocol”). 
4. Turn on recorder and state on the recording the participant study ID#. 
5. DISCLOSE RESULTS TO FAMILY. Answer questions specific to result disclosure discussion, 
being careful not to extend discussion into initiating additional care management plans 
(management examples may still be discussed, just not initiated during this encounter). 
6. Discuss next steps in SouthSeq for family to expect (see below “Next Steps” list). 
7. Find out if they remember their Genome Gateway username/password and website? If 
not, give it to them. If they don’t remember their password there is a link on the GG 
website they can click to re-set. (participants.southseq.org) 
8. Wrap up conversation. End Recording. 
9. Notify site study coordinator disclosure is finished, transfer call to study coordinator if 
available for post result surveys. 
Disclosure (in-person) 

2 
 
1. Make sure recording equipment is available and ready. 
2. Document who (all) attends disclosure and their relationship to proband. 
3. Read script from recording procedure and obtain permission to turn on recorder (see 
attached “Audio Recording Protocol”). 
4. Turn on recorder and state on the recording the participant study ID#. 
5. DISCLOSE RESULTS TO FAMILY. Answer questions specific to result disclosure discussion, 
being careful not to extend discussion into initiating additional care management plans 
(management examples may still be discussed, just not initiated during this visit). 
6. Discuss next steps in SouthSeq for family to expect (see attached “Next Steps” list). 
7. Find out if they remember their Genome Gateway username/password and website? If 
not, give it to them. If they don’t remember their password there is a link on the GG 
website they can click to re-set. (participants.southseq.org) 
8. Wrap up disclosure. End Recording. 
9. Notify site study coordinator disclosure is finished, study coordinator to come into the 
room to facilitate post result surveys. 
Follow-up 
1. Complete “Result Return” questionnaire in Genome Gateway (assigned to you by HA 
genetic counselor). If the questionnaire has not yet been assigned with the correct 
participant ID send a message to the HA genetic counselor to have it assigned. 
2. Give audio recorder back to site coordinator for audio file upload to HA 
3. Document results/disclosure clinically at institution. Pass result off to clinical team. 
 
Re-analysis/Amended Reports (if new information leads to change in result) 
1. Site coordinator will receive a message from HA GC that an amended report is available, 
with a copy of the amended report. 
2. Patient should be contacted with the new information (likely by phone, but any mode of 
communication is fine). Utilize audio recorder as described above. This re-contact does 
not have to be done by the same provider who did initial return, however the 
participant needs to remain the same study arm. 
3. Complete “Amended Result Return” questionnaire in Genome Gateway (assigned to you 
by HA genetic counselor). If the questionnaire has not yet been assigned to you with the 
correct participant ID send a message to the HA genetic counselor to have it assigned. 
4. Give audio recorder back to site coordinator for audio file upload to HA. 
5. Document results/disclosure clinically at institution (i.e note encounter in the EMR, 
upload result letter, etc.). Pass result off to clinical team. 
 
Next Steps (what participants can expect): 
 Surveys: 
 Encourage survey completion! 
 There is financial compensation for completion of surveys ($25/completed 
survey). 
 There are two brief surveys we will ask you to do on Genome Gateway right 
away after our conversation. 

3 
 
 At several points over the next several months there will be new surveys to 
complete in Genome Gateway (family will receive message/email/text when it is 
time). 
 Result Report: 
 A copy of the result report will be available to view/download in Genome 
Gateway within next couple of days. 
 A paper copy will also be mailed (if phone disclosure). 
 A copy will also be put in child’s medical record. 
 Education: 
 Some additional educational information about genetics and the result will be 
available in Genome Gateway a couple of days post-RoR (family will receive a 
message/email/text when they are available). 
 Educational materials can be accessed at any time in the future using Genome 
Gateway. 
 Clinical Follow-up: 
 If in-patient still can say that you will discuss result with [relevant doc] and they 
will make decisions about management. If out-patient, encourage patient to do 
whatever is needed to get looped into genetics/etc. Avoid doing clinical care 
during the research result disclosure. 
 Encourage patients to take copies of results reports to future appointments. 

4 
 
Audio Recording Protocol in SouthSeq 
1. Make sure recorder is charged/has power (prior to result appointment) 
 
2. At beginning of RoR session, prior to starting recording, say the following: 
 
“I want to remind you that as part of the SouthSeq study, we are audio-recording 
conversations about test results. The reason we are recording our meeting today is so that 
study researchers can learn more about how healthcare providers talk about genetics and 
describe test results. Only the study team will have access to the recording. Is it OK that I 
turn on the audio recorder now?” 
 
If yes  Turn on audio recorder and proceed with #5 
If no  Read this fallback text: 
“The study requests recording of the conversations when participants receive results. The 
reason for this request is that is important for the study to learn from our experiences and 
how we describe results to you. Is there anything else I can explain to make you more 
comfortable about it?” 
If yes  Answer questions and ask again for permission to turn on audio recorder 
If no  Is the participant in the standard of care arm (randomized to disclosure by genetics 
provider)? 
If yes (disclosure by genetics provider)  Proceed with #3 
If no (disclosure by non-genetics provider)  Proceed with #4 
 
3. The participant can opt-out of audio recording and still receive results at the current 
time. Put away the audio recorder and proceed with the disclosure of results. 
Following the disclosure, message the HudsonAlpha genetic counselor assigned to 
your site* to say that the participant (give study ID#) declined audio recording. Do 
not proceed with any further steps. 
 
4. The participant can opt-out of audio recording but unfortunately cannot receive 
results from a non-genetics provider without audio recording permission. Tell the 
family: 
 
“Unfortunately, because of our research plan and for your safety, I cannot discuss 
the results with you right now without using audio recording. If you choose to opt 
out of having this conversation recorded, we can have a genetic counselor for the 
study discuss the results with you at another time. Is that what you would like to 
do?” 

5 
 
If yes  Apologize for the inconvenience, tell them a study genetic counselor will be in 
touch soon, and that the results will be placed into the child’s medical record once the 
results have been discussed with the family. Notify the study coordinator at the site* 
and the HudsonAlpha genetic counselor assigned to your site of status. 
If no (would like to proceed with audio recording)  Proceed to step 5 
 
5. State the proband’s study ID# clearly on the recording, along with the date and the 
name of the provider doing the result return. 
 
6. Disclose the results to the participant family. Elicit and answer questions from the 
family. 
 
7. Once the result disclosure conversation is concluded, end the recording. 
8. Give audio recorder back to site coordinator/research nurse. 
 
9. Study Coordinator: Save the audio file to a secure, HIPAA compliant computer or 
storage drive using the study ID number as the file name, and upload the file within 
Genome Gateway to the HudsonAlpha genetic counselor assigned to your particular 
site.* This is done by selecting files on the left side menu, clicking on the person you 
want to send the file to from the list of people, and then clicking the “add file” button 
in the top right corner of the screen. This will allow you to select a file from your 
computer to send. 
 
10. Study Coordinator: Maintain an electronic, backup copy of all audio files on a 
computer prior to deleting the files from the recording device. 
 
11. HudsonAlpha genetic counselors: review the audio recording for disclosures in the 
experimental arm of the trial (disclosure by non-genetics provider). This review will 
occur within a week for negative results, within 72 business hours for positive and 
uncertain results and any errors will be tracked (minor errors, major errors, safety 
errors). All errors will be tracked for future aggregate analysis. Only major/safety 
errors will trigger real-time feedback to the disclosing provider from the genetic 
counselor. Store all audio files in a centralized, electronic location that is HIPAA 
compliant, organized by site, randomization arm, and study ID. 
 
*HudsonAlpha Genetic Counselor contacts by site: 
Alabama: Meagan Cochran 
Mississippi: Whitley Kelley 
Louisiana: Veronica Greve 

Statistical Analysis Plan 
 
Statistical Analysis:  Descriptive statistics were calculated by randomized group.  Specifically, for 
continuous demographic variables, sample means and standard deviations were calculated.  For 
categorical demographic variables, counts and sample proportions were calculated.  To test for differences 
between the randomized groups regarding demographics, two-sample tests were conducted for 
continuous variables and Chi-square analyses categorical outcomes.  Sample means and standard 
deviations were calculated by randomization group for the primary outcome (GCOS) and secondary 
outcomes (PUGS, PRU).  For all the outcomes, sample means and standard deviations were calculated by 
genetic testing results (none, variant of unknown significant, pathogenic) within each randomized group.  
Margin of noninferiority was set per outcome. To test non-inferiority, a one-tailed two-sample test 
comparing the difference of means, calculated as mean score outcome score of mother’s randomized to 
receive genetic results from genetic counselors minus the mean score outcome score of mother’s 
randomized to receive genetic results from non-genetic providers, to the non-inferiority margin was 
conducted.  The normality assumption was examined using normal-probability plots and histograms. The 
same testing strategy was used for stratified analyses to determine if non-inferiority could be declared by 
genetic result types.  All tests utilized a Type I error rate of 0.025 and were conducted in SAS 9.4. 
Primary outcome 
Results of the non-inferiority analysis for the primary outcome of GCOS are first presented by all 
genetic results combined for each group and then stratified by genetic result type. To conduct a non-
inferiority analysis, one must declare a difference between group means, called a non-inferiority 
margin, such that if the data provides statistically significant evidence that the difference of means is 
below that margin, then study can declare one group is non-inferior to the other. Non-inferiority 
designs are by design one-tailed hypothesis tests.  Within our study, we sought to demonstrate that the 
Nongenetic providers are non-inferior to Genetic Counselors.  We calculated the difference of means as 
the Genetic Counselor mean minus the NonGenetic Provider mean and based upon consultation with 
NIH, a non-inferiority margin of 10 points.  We have chosen to conduct the test using a Type I error rate 
of 0.025. As can be seen in the Results Section, the mean and standard deviation of the Genetic 
Counselor group is 117.94 ± 13.85 and the  mean and standard deviation of the Nongenetic Provider 
group is 117.19 ± 14.86.  The observed difference between mean is less than 1 point.  The test 
generates a p-value of <0.0001 when using a non-inferiority margin of 10.  Using a Type I error rate of 
0.025, we can conclude that nongenetic providers are non-inferior to genetic counselors when 
compared on the GCOS.  Because some clinicians may prefer to consider different non-inferiority 
margins, we have provided a one-tailed 97.5% confidence interval. For the combined genetic results, 
we are 97.5% confident that the true mean difference is less than 4.83 points.  Therefore, the 
noninferiority margin can be reduced to 4.83 and significance would still be declared.  However, if one 
insists on a margin of non-inferiority less than 4.83 points, our data would not provide sufficient 
evidence to declare non-inferiority.  As can be seen from the stratified analysis, non-inferiority can be 
declared for the genetic result strata of none and VUS.  However, the data does not provide sufficient 
evidence to declare nongenetic providers noninferior to genetic counselors when the genetic results 
are pathogenic. 
Secondary outcomes 
For secondary outcome of PUGS results are first presented by all genetic results combined for each group 
and then stratified by genetic result type. To conduct a non-inferiority analysis, one must declare a 
difference between group means, called a non-inferiority margin, such that if the data provides 
statistically significant evidence that the difference of means is below that margin, then study can declare 
one group is non-inferior to the other. Non-inferiority designs are by design one-tailed hypothesis tests.  
As mentioned above we sought to demonstrate that the Nongenetic providers are non-inferior to Genetic 

Counselors.  We calculated the difference of means as the Genetic Counselor mean minus the 
NonGenetic Provider mean and based upon consultation with NIH, a non-inferiority margin of 3.5 points.  
We have chosen to conduct the test using a Type I error rate of 0.025. As can be seen from the table, the 
mean and standard deviation of the Genetic Counselor group is 29.11 ± 7.31and the  mean and standard 
deviation of the Nongenetic Provider group is 29.74 ± 5.87.  The observed difference between mean is 
less than 1 point in favor of the nongenetic providers.  The test generates a p-value of <0.0001 when 
using a non-inferiority margin of 3.5.  Using a Type I error rate of 0.025, we can conclude that nongenetic 
providers are non-inferior to genetic counselors when compared on the PUGS.  Because some clinicians 
may prefer to consider different non-inferiority margins, we have provided a one-tailed 97.5% confidence 
interval. For the combined genetic results, we are 97.5% confident that the true mean difference is less 
than 1.22 points.  Therefore, the noninferiority margin can be reduced to 1.22 points and significance 
would still be declared.  However, if one insists on a margin of non-inferiority less than 1.22 points, our 
data would not provide sufficient evidence to declare non-inferiority.  As can be seen from the stratified 
analysis, non-inferiority can be declared for the all genetic result strata of none, VUS, and pathogenic.   
 
The results of the non-inferiority analysis for the secondary outcome of PRU are also first presented by all 
genetic results combined for each group and then stratified by genetic result type. To conduct a non-
inferiority analysis, one must declare a difference between group means, called a non-inferiority margin, 
such that if the data provides statistically significant evidence that the difference of means is below that 
margin, then study can declare one group is non-inferior to the other. Non-inferiority designs are by 
design one-tailed hypothesis tests.  Within our study, we seek to demonstrate that the Nongenetic 
providers are non-inferior to Genetic Counselors.  We calculated the difference of means as the Genetic 
Counselor mean minus the NonGenetic Provider mean and based upon consultation with NIH, a non-
inferiority margin of 10 points.  We have chosen to conduct the test using a Type I error rate of 0.025. As 
can be seen in the Results Section, the mean and standard deviation of the Genetic Counselor group is 
78.40 ± 20.51 and the  mean and standard deviation of the Nongenetic Provider group is 73.93 ± 19.86.  
The observed difference between mean is 4.47 points in favor of the genetic providers.  The test 
generates a p-value of 0.0277 when using a non-inferiority margin of 10.  Using a Type I error rate of 
0.025, we cannot conclude that nongenetic providers are non-inferior to genetic counselors when 
compared on the PRU.  Because some clinicians may prefer to consider different non-inferiority margins, 
we have provided a one-tailed 97.5% confidence interval. For the combined genetic results, we are 97.5% 
confident that the true mean difference is less than 10.13 points.  Therefore, the noninferiority margin 
would need to be increased to 10.13 points for significance to be declared. As can be seen from the 
stratified analysis, non-inferiority can be declared for pathogenic strata.