Evidence for linkage of Charcot-Marie-Tooth neuropathy to the Duffy locus on chromosome 1

Abstract

A linkage study was performed on three families with classic Charcot-Marie-Tooth (CMT) hereditary neuropathy with clinical manifestations of autosomal dominant inheritance, distal muscle weakness and atrophy, hyporeflexia, and slow motor nerve conduction velocities. Two families comprising 3 and 4 generations and a total of 23 affected persons were informative for the Duffy locus known to be on the long arm of chromosome 1. The maximum total lod score was 2.297 at recombination fraction theta = .1. The third family was informative for PGM1 (on the short arm of chromosome 1). There was no evidence for linkage of CMT to PGM1 in this third family, but only values of theta less than .03 could be excluded. There was no evidence for linkage of CMT to seven other informative markers in these families. We conclude that the gene controlling the occurrence of dominant CMT may be approximately 10 centimorgans from the Duffy locus on the long arm of chromosome 1. Additional studies are required to confirm these findings.