EVIDENCE FOR LINKAGE OF CHARCOT-MARIE-TOOTH NEUROPATHY TO THE DUFFY LOCUS ON CHROMOSOME-1

Abstract

A linkage study was performed on 3 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. = 0.1. The 3rd family was informative for PGM1 [phosphoglucomutase] (on the short arm of chromosome 1). There was no evidence for linkage of CMT to PGM1 in this 3rd family, but only values of .theta. < 0.03 could be excluded. There was no evidence for linkage of CMT to 7 other informative markers in these families. The gene controlling the occurrence of dominant CMT may be .apprx. 10 centimorgans from the Duffy locus on the long arm of chromosome 1. Additional studies are required to confirm these findings.