Clinical trial NCT01193088: Genetics of Charcot Marie Tooth (CMT) - Modifiers of CMT1A, New Causes of CMT2
Official title: Genetics of Charcot Marie Tooth Disease (CMT) - Modifiers of CMT1A, New Causes of CMT
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Charcot-Marie-Tooth Disease, Type Ia (Disorder)
HMSN
Keywords: CMT
CMT1A
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: Muscular Dystrophy Association
name: University of Rochester
name: University of Pennsylvania
name: King's College Hospital NHS Trust
name: Sydney Children's Hospitals Network
name: Children's Hospital of Philadelphia
name: University of Miami
name: Johns Hopkins University
name: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
name: Cedars-Sinai Medical Center
name: Nemours Children's Clinic
name: Stanford University
name: University of Minnesota
name: Massachusetts General Hospital
name: University of Colorado, Denver
name: Children's National Research Institute
name: University of Michigan
name: St. Jude Children's Research Hospital
name: Connecticut Children's Medical Center
name: Seattle Children's Hospital
name: The Hospital for Sick Children
First posted: 2010-09-01
Enrollment: 1050
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: Patients participating in Inherited Neuropathies Consortium (INC)-6601 and meeting eligibility criteria for this study will be recruited.

Brief summary: This project includes two projects. One is looking for new genes that cause Charcot Marie Tooth disease (CMT). The other is looking for genes that do not cause CMT, but may modify the symptoms a person has.

Detailed description: This project is to understand modifier genes and how they influence the severity of disease expression, along with identifying new forms of CMT which have not been genetically determined. Subjects who are eligible will either have CMT type 1A (CMT1A) or an unknown form of CMT. Blood will be drawn and sent to the University of Miami where they receive the coded sample and process it through exome sequencing. Subjects will be told that this is optional.

Eligibility criteria: Inclusion Criteria:

All patients must agree to take part in the study and sign a consent form. A teenager (age 13-17 years) considering enrolling must agree to take part in the study and sign an assent form (depending on local ethics committee requirements).

Additional inclusion criteria are described below.

Inclusion Criteria: CMT1A Gene Modifier Study

Patients must have at least one of the following:

1. Patient has a documented PMP22 duplication. AND/OR
2. Patient has a first or second degree relative (parent, child, sibling, half- sibling, aunt, uncle, grandparent, grandchild, niece, or nephew) with a documented PMP22 duplication AND a clear link between that family member and the affected patient AND a phenotype consistent with CMT1A.

i. A clear link is necessary for a second-degree relative. For example, if a grandparent is affected and has a PMP22 duplication, and the parent does not have any signs, symptoms, or electrophysiology consistent with CMT1A, there is no clear link.

ii. In cases where clear links are not available, genetic testing is required for the patient or the first degree family member who is not clearly affected.

Inclusion Criteria - Patients for CMT Exome Project

a. Patient has demonstrated neuropathy on nerve conduction studies or clinically diagnosed genetic neuropathy, in the opinion of the investigator or genetic counsellor.

Inclusion Criteria - Controls for CMT Exome Project

1. Person is a family member of a CMT patient who is enrolled in the CMT Exome Project.

   AND one of the following:
2. Person does not have a peripheral neuropathy, in the opinion of the investigator or genetic counsellor.

   OR
3. Person is suspected to have a peripheral neuropathy, but has not been examined at an INC site.

Exclusion Criteria

1. Patient does not wish to participate or does not sign a consent form.
2. For CMT Exome Project, patient has a genetically confirmed form of CMT (i.e. mutation in MFN2 causing CMT2A, mutation in GARS causing CMT2D, etc.).
3. Patients with known neuropathy from a non-genetic source, such as chemotherapies (i.e. Vincristine, Taxol, Cisplatin), diabetes, alcoholism will be evaluated independently so that genetic contributions to their effects on CMT1A phenotypes can also be analyzed.

Primary outcomes:
measure: Charcot Marie Tooth disease type 1A (CMT1A) gene modifiers
timeFrame: once
measure: New genetic causes of CMT
timeFrame: Once
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Harvard/Massachusetts General Hospital
state: Massachusetts
city: Maple Grove
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Sydney
country: Australia
facility: Children's Hospital of Westmead
state: New South Wales
city: Milan
country: Italy
facility: C. Besta Neurological Institute
city: London
country: United Kingdom
facility: National Hospital of Neurology and Neurosurgery
state: England
city: London
country: United Kingdom
facility: Dubowitz Neuromuscular Centre
Study officials:
affiliation: University of Iowa
name: Michael E Shy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Montenegro G, Powell E, Huang J, Speziani F, Edwards YJ, Beecham G, Hulme W, Siskind C, Vance J, Shy M, Zuchner S. Exome sequencing allows for rapid gene identification in a Charcot-Marie-Tooth family. Ann Neurol. 2011 Mar;69(3):464-70. doi: 10.1002/ana.22235. Epub 2011 Jan 20.