CMT is a disease of the peripheral nerves. The peripheral nerves are every nerve that lie outside the brain and spinal cord with the exception of the optic nerves, and CMT affects every one of these. CMT is caused by a mutation in any one of 140 different genes, and the number of genes continues to grow. A gene mutation that causes CMT disrupts a molecular process within the peripheral nerves. The mutation alters the gene’s function—how it works, causing the gene to behave abnormally. It’s akin to substituting powdered sugar in place of brown sugar in your favorite cookie recipe. Sure, you’ll still get a cookie, but the cookie just 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.
A gene that’s been discovered to have CMT-causing mutations 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).
Most CMT subtypes are caused by a single mutation within their associated gene. Others are caused by having two mutations within their associated gene. When the subtype is caused by having just one mutation within the gene, and the gene lives on a numbered chromosome (1-22—the autosomes), the subtype is considered autosomal dominant. When the subtype is caused by having two mutations within the gene, and the gene lives 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.
