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

NCT01193088 | Recruiting DMC

• 2 other identifiers: INC-66021U54NS065712-01
• Study Type: observational
• Target: 1,050
• Locations: 5 countries
• Sites: 22

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.

Conditions

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

Keywords

CMT; CMT1A

Outcome Measures

Primary Outcomes (2)

• Charcot Marie Tooth disease type 1A (CMT1A) gene modifiers

  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.

  once

• New genetic causes of CMT

  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.

  Once

Study Arms (2)

CMT1A

Families/people with genetically defined CMT1A

Genetically undefined CMT

Families/people with genetically undefined CMT with common causes ruled out.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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).
• 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.
• a. Patient has demonstrated neuropathy on nerve conduction studies or clinically diagnosed genetic neuropathy, in the opinion of the investigator or genetic counsellor.
• Person is a family member of a CMT patient who is enrolled in the CMT Exome Project.
• AND one of the following:
• Person does not have a peripheral neuropathy, in the opinion of the investigator or genetic counsellor.
• Person is suspected to have a peripheral neuropathy, but has not been examined at an INC site.

You may not qualify if:

• Patient does not wish to participate or does not sign a consent form.
• 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.).
• 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.

Sponsors & Collaborators

• University of Iowa: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Muscular Dystrophy Association: collaborator
• University of Rochester: collaborator
• University of Pennsylvania: collaborator
• King's College Hospital NHS Trust: collaborator
• Sydney Children's Hospitals Network: collaborator
• Children's Hospital of Philadelphia: collaborator
• University of Miami: collaborator
• Johns Hopkins University: collaborator
• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: collaborator
• Cedars-Sinai Medical Center: collaborator
• Nemours Children's Clinic: collaborator
• Stanford University: collaborator
• University of Minnesota: collaborator
• Massachusetts General Hospital: collaborator
• University of Colorado, Denver: collaborator
• Children's National Research Institute: collaborator
• University of Michigan: collaborator
• St. Jude Children's Research Hospital: collaborator
• Connecticut Children's Medical Center: collaborator
• Seattle Children's Hospital: collaborator
• The Hospital for Sick Children: collaborator

Study Sites (22)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Stanford University

Palo Alto, California, 94304, United States

RECRUITING

University of Colorado Hospital

Aurora, Colorado, 80045, United States

RECRUITING

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21205, United States

RECRUITING

Harvard/Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

University of Minnesota

Maple Grove, Minnesota, 55369, United States

RECRUITING

University of Rochester

Rochester, New York, 14642, United States

RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

Children's Hospital of Westmead

Sydney, New South Wales, 2145, Australia

RECRUITING

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

RECRUITING

C. Besta Neurological Institute

Milan, Italy

RECRUITING

National Hospital of Neurology and Neurosurgery

London, England, WC1N 3BG, United Kingdom

RECRUITING

Dubowitz Neuromuscular Centre

London, United Kingdom

RECRUITING

Related Publications (1)

• 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.

  PMID: 21254193 RESULT

Related Links

• Inherited Neuropathies Consortium Website

Biospecimen

Retention: SAMPLES WITH DNA

DNA extracted from whole blood. Filter cards with blood spots.

MeSH Terms

Conditions

Charcot-Marie-Tooth Disease; Hereditary Sensory and Motor Neuropathy

Condition Hierarchy (Ancestors)

Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Michael E Shy, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tiffany Grider, MS, CGC

CONTACT

319-384-6362; UICMTClinic@uiowa.edu

Nicole Kressin, MS, CGC

CONTACT

319-384-6362; UICMTClinic@uiowa.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 9, 2010
• First Posted: September 1, 2010
• Study Start: May 1, 2010
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 7, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: (For Observational/Longitudinal/Natural History/Epidemiology studies): For the current grant cycle, available data will be released to the repository and will become available to the scientific community one year after publication of planned analyses, or after a period of 5 years from the date when the data were collected, whichever comes first.
• Access Criteria: \- For the current grant cycle, once de-identified data is posted on dbGaP, a summary of the study is posted and individual participant data is accessed via a request through dbGaP.

Locations

US (17); AU (1); CA (1); GB (2); IT (1)