Mapping of Charcot-Marie-Tooth disease type 1C to chromosome 16p identifies a novel locus for demyelinating neuropathies

Charcot-Marie-Tooth (CMT) neuropathy represents a genetically heterogeneous group of diseases affecting the peripheral nervous system. We report genet ic mapping of the disease to chromosome 16p13.1-p12.3, in two families with autosomal dominant CMT type 1C (CMT1C). Affected individuals in these fami lies manifest characteristic CMT symptoms, including high-arched feet, dist al muscle weakness and atrophy, depressed deep-tendon reflexes, sensory imp airment, slow nerve conduction velocities, and nerve demyelination. A maxim al combined LOD score of 14.25 was obtained with marker D16S500. The combin ed haplotype analysis in these two families localizes the CMT1C gene within a 9-cM interval flanked by markers D16S519 and D16S764. The disease-linked haplotypes in these two pedigrees are not conserved, suggesting that the g ene mutation underlying the disease in each family arose independently. The epithelial membrane protein 2 gene (EMP2), which maps to chromosome 16p13. 2, was evaluated as a candidate gene for CMT1C.