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April 2003

Genetics of Charcot-Marie-Tooth Disease

Arch Neurol. 2003;60(4):481-482. doi:10.1001/archneur.60.4.481

CHARCOT-MARIE-TOOTH DISEASE (CMT) rivals neurofibromatosis type 1 as the most common genetic disorder affecting the peripheral nervous system. In the United States, Western Europe, and Japan, the most frequent mutation causing CMT is a reduplication of a 15-megabase segment of DNA on chromosome 17.1 The mechanism by which this duplication leads to dominantly inherited demyelinative polyneuropathy (CMT1A) is likely via overexpression of the peripheral myelin protein 22 gene (PMP22), which is located on the duplicated chromosomal segment.2 Various mutations affecting the myelin protein zero (P0) or connexin 32 (Cx32) genes are also relatively common causes of CMT. P0 mutations occur as either dominant or recessive genes; they primarily affect myelin but in some instances show predominantly axonal abnormalities.1,3Cx32 mutations are inherited in an X-linked pattern and typically yield mixed axonal and myelin sheath abnormalities.1 Mutations in these and other genes that cause CMT are listed on the Web site http://molgen-www.uia.ac.be/CMTMutations/.

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