Charcot - Marie Tooth Disease



CHARCOT-MARIE TOOTH DISEASE (CMT), in all of its forms, is the most commonly inherited peripheral neuropathy in humans, with a total prevalence rate of 1 in 2,500. The most common form is CMT1A, in which the average age of onset of clinical symptoms is around 12 years. .


CMT1A is most often caused by duplication of a ~1.5 Mb region on chromosome 17p11.2. A deletion of the same region causes hereditary neuropathy with liability to pressure palsies (HNPP). Duplication or deletion of this chromosomal region is a result of unequal crossing over between two 24 kb CMT1A-REP repeated sequences that flank this region. Increased gene dosage of the PMP22 gene, influencing nerve conduction velocity, is the main cause of the clinical manifestations of CMT1A. The PMP22 gene encodes the peripheral myelin protein 22. Duplication of PMP22 may be found in up to 70% of inherited and 90% of sporadic cases of CMT type 1. Deletion of this region is found in 85% of HNPP cases. The majority of individuals with the HNPP deletion probably remain undiagnosed due to ascertainment bias secondary to the mild phenotype (Lupski, J.R. et al. (1993) J. Am. Med. Ass., 270, 2326-2330). Larger regions of duplication or point mutations in PMP22 can also cause CMT1A. Clinically normal adult CMT1A “patients” are rare, but do exist.


This P033-B3 CMT1 probemix contains probes for the PMP22, COX10, & TEKT3 genes located in the CMT/HNPP region at 17p12. Probes for each of the five PMP22 exons are present in this probemix. In addition, this probemix contains several probes just outside the CMT/HNPP region for reference. Finally, 2 probes for KIF1B are included. Defects in the KIF1B gene have been implicated in Charcot Marie disease type 2A1