Assignment of a second Charcot-Marie-Tooth type II locus to chromosome 3q

Abstract

Charcot-Marie-Tooth disease (CMT) is the most common inherited motor and sensory neuropathy. The neuronal form of this disorder is referred to as Charcot-Marie-Tooth type II disease (CMT2). CMT2 is usually inherited as an autosomal dominant trait with a variable age at onset of symptoms associated with progressive axonal neuropathy. In some families, the locus that predisposes to CMT2 has been demonstrated to map to the distal portion of the short arm of chromosome 1. Other families with CMT2 do not show linkage with 1p markers, suggesting genetic heterogeneity in CMT2. We investigated linkage in a single large kindred with autosomal dominant CMT2. The gene responsible for CMT2 in this kindred (CMT2B) was mapped to the interval between the microsatellite markers D3S1769 and D3S1744 in the 3q13-22 region. Study of additional CMT2 kindreds should serve to further refine the disease gene region and may ultimately lead to the identification of a gene defect that underlies the CMT2 phenotype.