Genetic linkage with chromosome 19 but not chromosome 17 in a family with myotonic dystrophy associated with hereditary motor and sensory neuropathy

Abstract

We identified a large kindred that shows classical myotonic dystrophy (MyD), together with hereditary motor and sensory neuropathy (HMSN) in some individuals, and HMSN alone in others. A previous study of this family has shown cosegregation of the MyD and HMSN phenotypes with the Lutheran and secretor loci in some branches of the family, indicating linkage to chromosome 19. We reanalyzed this family with 2 recombinant DNA marker systems from the ApoC2 locus on chromosome 19. Our results demonstrate that all affected individuals have inherited a unique ApoC2 haplotype that was not found in their clinically and electrophysiologically normal sibs. We also obtained evidence against involvement of the HMSN I locus on chromosome 17. In this family, a moderately severe neuropathy may be the only clinical sign of MyD for many years. Our results are consistent with an unusual neuropathic mutation at the MyD gene. However, involvement of 2 closely linked genes (1 for MyD and the other for HMSN) can also explain our findings.