The DM mutation; diagnostic applications in the Finnish population

A pair of marker loci, D19S63 and D19S51, which are tightly linked to the myotonic dystrophy (DM) locus, were used to evaluate diagnostic applicability in the Finnish population. Results were then compared to direct detection of the mutation. The D19S63 locus revealed a linkage disequilibrium, since in 16 DM families as many as 75% of DM chromosomes carried the same allele 3 for D19S63, and 25% carried allele 1. However, when the data for D19S51 and D19S63 were considered together as a haplotype, the statistical significance of this linkage disequilibrium was considerably reduced. As expected, the best method for reliable evaluation of the carrier risk was direct analysis of the mutation. Thirteen particularly difficult cases were resolved and in 46% of them the decision could be made only by direct visualization of the mutation. However, in a few cases where the size of the CTG-repeat expansion was close to the normal size range, linked markers proved to be useful to determine the affected chromosomes. Present findings indicate that analysis of the D19S63 locus coupled to direct demonstration of the mutation provides the basis for DNA diagnostics of DM in the Finnish population.