Further evidence for a major ancient mutation underlying myotonic dystrophy from linkage disequilibrium studies in...

The myotonic dystrophy (DM) mutation is an unstable (CTG)n repeat, present at a copy number of 5-37 repeats on normal chromosomes but amplified to 50-3000 copies on DM chromosomes. Previous findings in Caucasian populations of a DM founder chromosome raise a question about the molecular events involved in the expansion mutation. To investigate whether a founder chromosome for the DM mutation exists in the Japanese population, we genotyped families using polymorphic markers near the (CTG)n repeat region and constructed haplotypes. Six different haplotypes were found and DM alleles were always haplotype A. To find an origin of the (CTG)n repeat mutation and to investigate the mechanism of the expansion mutation in the Japanese population we have studied 90 Japanese DM families comprising 190 affected and 130 unaffected members. The results suggest that a few common ancestral mutations in both Caucasian and Japanese populations have originated by expansion of an ancestral n = 5 repeat to n = 19-37 copies. These data support multistep models of triplet repeat expansion that have been proposed for both DM and Friedreich's ataxia.