Genetics of Charcot Marie Tooth Disease (CMT) - Modifiers of CMT1A, New Causes of CMT
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Charcot-Marie-Tooth Disease, Type Ia (Disorder)
- Sponsor
- University of Iowa
- Enrollment
- 1050
- Locations
- 22
- Primary Endpoint
- New genetic causes of CMT
- Status
- Recruiting
- Last Updated
- 6 months ago
Overview
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.
Investigators
Michael Shy
Professor
University of Iowa
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:
- •Patient has a documented PMP22 duplication. AND/OR
- •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.
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
New genetic causes of CMT
Time Frame: 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.
Charcot Marie Tooth disease type 1A (CMT1A) gene modifiers
Time Frame: 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.