ASSIGNMENT OF A 2ND CHARCOT-MARIE-TOOTH TYPE-II LOCUS TO CHROMOSOME-3Q

Charcot-Marie-Tooth disease (CMT) is the most common inherited motor a nd sensory neuropathy. The neuronal form of this disorder is referred to as Charcot-Marie-Tooth type II disease (CMT2). CMT2 is usually inhe rited as an autosomal dominant trait with a variable age at onset of s ymptoms associated with progressive axonal neuropathy. In some familie s, the locus that predisposes to CMT2 has been demonstrated to map to the distal portion of the short arm of chromosome 1. Other families wi th CMT2 do not show linkage with Ip markers, suggesting genetic hetero geneity in CMT2. We investigated linkage in a single large kindred wit h autosomal dominant CMT2. The gene responsible for CMT2 in this kindr ed (CMT2B) was mapped to the interval between the microsatellite marke rs D3S1769 and D3S1744 in the 3q13-22 region. Study of additional CMT2 kindreds should serve to further refine the disease gene region and m ay ultimately lead to the identification of a gene defect that underli es the CMT2 phenotype.