CMT is caused by mutations in any one of more than 140 different genes, and the number continues to grow. These mutations disrupt a molecular process within the peripheral nerves, which are the nerves that lie outside the brain and spinal cord, except for the optic nerves. Each mutation alters the gene’s function, causing it to behave abnormally. It’s akin to substituting powdered sugar for brown sugar in your favorite cookie recipe. Sure, you’ll still get a cookie, but it won’t be the same. Extend this to the peripheral nerves, and sure, you still get peripheral nerves, but they just aren’t the same.
What Is a CMT-Associated Gene?
A gene identified as causing CMT is called a “CMT-associated gene.” Some CMT-associated genes have just one lonely mutation that’s known to cause CMT. Most, however, have many individual mutations that each cause CMT, while some have hundreds of individual mutations that each cause CMT, such as the GJB1 gene, which has over 400 discovered mutations that each cause CMTX1 (aka CMT1X, CMTX).
Dominant vs Recessive
Most CMT subtypes are caused by a single mutation within their associated gene. Others are caused by having two mutations within their gene. When the subtype is caused by a single mutation in a gene on a numbered chromosome (1-22—the autosomes), the subtype is considered autosomal dominant. When the subtype is caused by two mutations within a gene on a numbered chromosome, the subtype is considered autosomal recessive. Likewise, one mutation in a gene that lives on an X-chromosome is considered X-Linked dominant, and two mutations is X-Linked recessive. Each of these are also an inheritance pattern. An inheritance pattern is how the CMT-causing mutation is passed on/inherited, and each have their own rules governing the chances of passing on/inheriting the mutation.
