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NCT01193088RecruitingAccepts Healthy Volunteers

Genetics of Charcot Marie Tooth (CMT) - Modifiers of CMT1A, New Causes of CMT2

University of Iowa

Start Date

5/1/2010

Completion Date

12/1/2026

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

Age Range: No minimum to No maximum

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.

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Conditions

Charcot-Marie-Tooth Disease, Type Ia (Disorder)HMSN

Locations

Cedars-Sinai Medical Center

Los Angeles, California 90048

United States

Stanford University

Palo Alto, California 94304

United States

University of Colorado Hospital

Aurora, Colorado 80045

United States

Connecticut Children's Medical Center

Hartford, Connecticut 06106

United States

University of Miami

Miami, Florida 33136

United States

University of Iowa

Iowa City, Iowa 52242

United States

Johns Hopkins University

Baltimore, Maryland 21205

United States

Harvard/Massachusetts General Hospital

Boston, Massachusetts 02114

United States

University of Michigan

Ann Arbor, Michigan 48109

United States

University of Minnesota

Maple Grove, Minnesota 55369

United States

University of Rochester

Rochester, New York 14642

United States

University of North Carolina

Chapel Hill, North Carolina 27599

United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania 19104

United States

University of Pennsylvania

Philadelphia, Pennsylvania 19104

United States

St. Jude Children's Research Hospital

Memphis, Tennessee 38105

United States

Houston Methodist Hospital

Houston, Texas 77030

United States

Seattle Children's Hospital

Seattle, Washington 98105

United States

Children's Hospital of Westmead

Sydney, New South Wales 2145

Australia

The Hospital for Sick Children

Toronto, Ontario M5G 1X8

Canada

C. Besta Neurological Institute

Milan,

Italy

National Hospital of Neurology and Neurosurgery

London, England WC1N 3BG

United Kingdom

Dubowitz Neuromuscular Centre

London,

United Kingdom