Charcot-Marie-Tooth disease (CMT)

Charcot-Marie-Tooth disease (CMT) c.rowland Wed, 04/01/2020 - 11:12

These mutations usually affect the production of a particular protein in the peripheral nerves, either causing the protein to be faulty or not produced at all. How this then leads to damage of the peripheral nerves is not well understood for all types of CMT, however, many researchers around the world are looking into this. The most common sub-type of CMT is CMT 1A. It is usually caused by the duplication of a gene on chromosome number 17.

This gene carries the instructions for a protein found in myelin, called peripheral myelin protein 22 (PMP-22). Individuals with this condition have an extra copy of PMP-22 (three copies instead of the usual two) because they have an extra copy of a small part of chromosome 17 containing the PMP-22 gene. Although this mutation, commonly called the chromosome 17 duplication, is usually inherited in an autosomal dominant manner, it has been found in some individuals with healthy parents and thus represents a new mutation. More rarely, people with CMT1A have a change in, rather than a duplication of, the PMP-22 gene.

How is CMT inherited?

There are different inheritance patterns for different types of CMT. Most sub-types of CMT type 1 are inherited in an autosomal dominant manner. This means that you only need to inherit the faulty gene from one parent to have the condition. CMT X1 is the only exception in the type 1 category – it has X-linked inheritance, which means it is determined by a gene carried on the X chromosome (one of the sex chromosomes).

As males have only one X chromosome, and females have two, males tend to be much more severely affected by CMT X1 than females. Although most sub-types of CMT type 2 are autosominal dominant, there are a few rare sub-types that are inherited in an autosominal recessive manner. This means that you need to inherit the faulty gene from both parents to have the condition. For more explanation on the different patterns of inheritance, please see our Inheritance factsheet.

https://mduk-resources-stage.s3.eu-west-1.amazonaws.com/pdf/factsheets/Charcot-Marie-Tooth-disease-CMT.pdf