Charcot-Marie-Tooth Disease, Type Ia (Disorder), HMSN
Conditions
Keywords
CMT, CMT1A
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.
Interventions
None listed
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Muscular Dystrophy Association
University of Rochester
University of Pennsylvania
King's College Hospital NHS Trust
Sydney Children's Hospitals Network
Children's Hospital of Philadelphia
University of Miami
Johns Hopkins University
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Cedars-Sinai Medical Center
Nemours Children's Clinic
Stanford University
University of Minnesota
Massachusetts General Hospital
University of Colorado, Denver
Children's National Research Institute
University of Michigan
St. Jude Children's Research Hospital
Connecticut Children's Medical Center
Seattle Children's Hospital
The Hospital for Sick Children
University of Iowa
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Charcot Marie Tooth disease type 1A (CMT1A) gene modifiers | once | While the same genetic change - an extra copy of PMP22 - causes CMT1A by definition, it is unclear why some people have more severe symptoms and some have less severe. We are looking for genetic modifiers - changes in the DNA that may be causing the differences in symptoms. |
| New genetic causes of CMT | Once | At least 33% of people with CMT have an unknown or genetically un-found form of the condition. We are looking for additional genes that cause CMT when mutated. |
Countries
Australia, Canada, Italy, United Kingdom, United States
Contacts
Primary ContactTiffany Grider, MS, CGC
Backup ContactNicole Kressin, MS, CGC
Outcome results
None listed