Medicine
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Charcot-Marie-Tooth disease (CMT) was initially described more than 100 years ago by Charcot, Marie, and Tooth. It was only recently, however, that molecular genetic studies of CMT have uncovered the underlying causes of most forms of the diseases. Most cases of CMT1 are associated with a 1.5-Mb tandem duplication in 17p11.2-p12 that encompasses the PMP22 gene. ⋯ The discovery of the PMP22 gene in the 1.5-Mb CMT1A duplication/HNPP deletion critical region also suggests that the clinical phenotype of chromosome aneuploid syndromes may result from the effect of a small subset of dosage-sensitive genes mapping within the region of aneuploidy. The understanding of the molecular basis of CMT1 and related disorders has allowed accurate DNA diagnosis and genetic counseling of inherited peripheral neuropathies and will make it possible to develop rational strategies for therapy. As several loci for CMT2 have been identified, the genes responsible for CMT2 will most likely be disclosed using positional cloning and candidate gene approaches in the near future.