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6602: Genetics of CMT- Modifiers of CMT1A, New Causes of CMT

Study Summary

Please Note: The Rare Diseases Clinical Research Network will make every effort to enroll all the patients we can, but we cannot make any guarantees that we will be able to enroll everyone in a particular study who wants to participate.


Charcot Marie Tooth disease (CMT) is an umbrella term that covers any inherited peripheral neuropathy. People with CMT have a problem with the nerves that go to the feet and hands that cause muscle and sensation loss, as well as difficulty with balance. There are two aims of this study: finding genetic modifiers for CMT1A, and finding new genes that cause CMT.

All people with CMT1A have the same duplication of the PMP22 gene. However, the symptoms that a person with CMT1A experiences can range from mild to severe. We are looking at the DNA and impairment of 1000 people to see if we can find other genetic causes that modify their CMT1A symptoms.

While many of the genes that cause CMT when mutated have been discovered, there are still many types of CMT for which the genetic cause is unknown. We are looking at small families who have forms of CMT that have not been identified by genetic testing to see if we can find the cause for their CMT.

The research questions are:

  1. Are their genes that influence the symptoms of CMT1A?
  2. Can we identify new causes of CMT using small families with an unknown cause to their CMT?

About this Study

This is a study where we are collecting DNA from subjects once. We are looking to collect DNA and clinical information (as part of study 6601) on 1000 patients with CMT1A. You may be enrolled in study 6601 for an extended period of time, but the involvement for this study (6602) is a one time event. For small families (about 3 people) with unidentified forms of CMT, we will be enrolling 20 families. This is also a one-time event. Enrollment includes entry into study 6601, and agreement to take part in 6602. For this study, we require a blood draw, where three tubes of blood will be taken.

Targeted Enrollment

To be eligible to participate, you must:

For the CMT1A Gene Modifier Study:

  • Have genetically confirmed CMT1A, or have a first- or second-degree family member who has genetically confirmed CMT1A and have nerve conduction velocities in the demyelinating range.

For the New Causes of CMT Project:

  • You have a neuropathy on nerve conduction studies or a clinically diagnosed genetic neuropathy AND
  • You or a first- or second-degree family member have had negative genetic testing for MFN2 if you have an axonal form of CMT (nerve conductions greater than 38 m/s in the arms), or negative genetic testing for PMP22 duplication, deletion, sequencing, MPZ, and GJB1 if a demyelinating form of CMT is present (38 m/s) AND
  • More than one additional family member is also willing to participate. One family member must be at least a second degree relative of one of the other participants (grandparent, uncle, aunt, niece, nephew, or half-sibling). Only one family member can be a first degree relative (parent, child, sibling).
    • Participation involves the other family members also agreeing to participate, enrolling in study 6601 – Natural History Evaluation of Charcot Marie Tooth disease, and provided a blood sample for DNA extraction.

You are not eligible to participate if:

  • You have a known neuropathy from a non-genetic source, such as chemotherapies, diabetes, or alcohol.
  • For the New Causes of CMT study, only full families of at least 3 people who match the inclusion criteria will be eligible.
  • For the New Causes of CMT study, if a known genetic cause of the CMT in the family has been found, that family is not eligible.

How to participate

In order to participate in a study, you must personally contact the study coordinator of any of the participating institutions by phone or by e-mail. Please use the information to the right to inquire about participation.