Clinical trial NCT05783791: Development of a Newborn Screening Assay for Angelman Syndrome and Prader-Willi Syndrome
Official title: Development of a Newborn Screening Assay for Angelman Syndrome and Prader-Willi Syndrome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Angelman Syndrome
Prader-Willi Syndrome
Keywords: Newborn Screening
Assay
Public Health
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: Ultragenyx Pharmaceutical Inc
First posted: 2023-03-24
Enrollment: 11
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will target three groups:

* participants with Angelman Syndrome
* participants with Prader-Willi Syndrome
* healthy controls

Brief summary: The overall purpose of this project is to establish the capability of screening for Angelman syndrome (AS) and Prader-Willi syndrome (PWS) in public health newborn screening (NBS) programs, with an aim of developing and validating a screening test for AS and PWS.

Detailed description: This project will have an assay development phase and an assay validation phase.

In the assay development phase, the investigators will develop a method of assessing SNRPN promoter (located in chromosome 15 q11-q13) methylation status using methylation-specific PCR coupled with a melting curve analysis with de-identified leftover DNA from routine newborn screening dried blood samples for severe combined immunodeficiency and spinal muscular atrophy.

In the assay validation phase, the investigators plan to assess the assay sensitivity and specificity using a set of DNA samples extracted from dried blood spots in each following group:

1. Healthy individuals
2. AS patients with genetic testing confirmation that the maternal copy of chromosome 15 q11-q13 is deleted, or that there are two paternal copies of chromosome 15 q11-q13 or imprinting center defect.
3. PWS patients with genetic testing confirmation that the paternal copy of chromosome 15 q11-q13 is deleted, or that there are two maternal copies of chromosome 15 q11-q13 or imprinting center defect.

For participants with AS or PWS, blood samples will be obtained via a self-administered finger prick performed in the participant's home. The participant will mail the sample to the researchers using a provided envelope. If the team is not able to reach the participant after two phone call attempts, the study team may approach them at their next clinic visit to assess interest in study participation. If participants opt to join the study at this clinic visit, the blood sample may be obtained in clinic.

For healthy controls, blood samples will be obtained via a self-administered finger prick, and participants will verbally respond to a brief demographic questionnaire.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with Angelman Syndrome, confirmed by molecular testing (deletion of maternal allele of chromosome 15q11-q13, paternal uniparental disomy, and imprinting center defects)
* Diagnosed with Prader-Willi Syndrome, confirmed by molecular testing (deletion of paternal allele of chromosome 15q11-q13, maternal uniparental disomy, and imprinting center defects)
* Angelman Syndrome or Prader Willi Syndrome: Current patient at UW Health in the Madison, Wisconsin metropolitan area
* Healthy controls 18 years old or older and have not received a diagnosis of Angelman syndrome or Prader Willi syndrome

Exclusion Criteria:

* Angelman Syndrome/Prader Willi Syndrome: family requires a translator for medical visits
* Healthy Controls: Participants are unable to consent and complete study procedures in English.

Primary outcomes:
measure: Sensitivity: Number of True Positive AS Results
timeFrame: 1 sample collected from participant either at home or in presence of a study team member at clinic, up to 5 minutes
measure: Sensitivity: Number of True Positive PWS Results
timeFrame: 1 sample collected from participant either at home or in presence of a study team member at clinic, up to 5 minutes
measure: Specificity: Number of Healthy Controls With True Negative Results
timeFrame: 1 sample collected from participant in presence of a study team member (controls), up to 5 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin School of Medicine and Public Health
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Mei W Baker, M.D., FACMG
role: PRINCIPAL_INVESTIGATOR
References: