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Recruiting NCT01193088

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

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

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
This is an observational study: the protocol does not assign a study treatment.
Who it may be relevant to
Registry conditions: Charcot-Marie-Tooth Disease, Type Ia (Disorder), HMSN. Basic parameters: No limits · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States, Australia, Canada, Italy, United Kingdom
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

Primary outcome measures

  • Charcot Marie Tooth disease type 1A (CMT1A) gene modifiers [Time frame: once]
  • New genetic causes of CMT [Time frame: Once]

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.

Inclusion Criteria - Controls for CMT Exome Project

  • 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.

OR

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

Exclusion criteria

  • 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model
Cohort

Study locations

United States · 17 centers
  • Cedars-Sinai Medical Center — Los Angeles
  • Stanford University — Palo Alto
  • University of Colorado Hospital — Aurora
  • Connecticut Children's Medical Center — Hartford
  • University of Miami — Miami
  • University of Iowa — Iowa City
  • Johns Hopkins University — Baltimore
  • Harvard/Massachusetts General Hospital — Boston
  • … and 9 more centers
United Kingdom · 2 centers
  • National Hospital of Neurology and Neurosurgery — London
  • Dubowitz Neuromuscular Centre — London
Australia · 1 center
  • Children's Hospital of Westmead — Sydney
Canada · 1 center
  • The Hospital for Sick Children — Toronto
Italy · 1 center
  • C. Besta Neurological Institute — Milan

Publications

  • 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

Identifiers

NCT: NCT01193088 · INC-6602 · 1U54NS065712-01

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗