GENETIC-HETEROGENEITY IN CHARCOT-MARIE-TOOTH NEUROPATHY TYPE-2

Charcot-Marie-Tooth neuropathy type 2 (CMT2) is a common inherited axo nal neuropathy. The locus for one form of CMT2 (CMT2A) is assigned to the short arm of chromosome 1. There is genetic heterogeneity in CMT2 because additional pedigrees do not demonstrate linkage to chromosome 1 and are designated as CMT2B. Further clinical heterogeneity is sugge sted by CMT2 pedigrees with diaphragm and vocal cord weakness and are designated as CMT2C. To address the possible genetic distinction betwe en CMT2A and CMT2C, we tested markers from the CMT2A locus for linkage in a large CMT2C pedigree. There was no evidence to support linkage o f the CMT2C gene to the region of the CMT2A locus on chromosome 1. CMT 2C is not an allelic variant of CMT2A. This analysis provides further evidence for genetic heterogeneity within inherited axonal neuropathie s.