DIRECT MOLECULAR ANALYSIS OF MYOTONIC-DYSTROPHY IN THE GERMAN POPULATION - IMPORTANT CONSIDERATIONS IN GENETIC-COUNSELING

Myotonic dystrophy (DM) is associated with the expansion and instabili ty of a trinucleotide (CTG) repeat at the DIM locus on chromosome 19. Direct genomic analysis in the German population was carried out on 18 DM families, six families with equivocal diagnosis, 69 subjects with equivocal clinical diagnosis, and 100 controls using the polymerase ch ain reaction (PCR) and a refined Southern protocol. In the majority of the cases molecular analysis confirmed the clinical diagnosis. These included seven cases of congenital DM (CDM) with widely differing gene expansions and instabilities. In most DM families the expanded fragme nt became larger in successive generations, but we also identified fou r families with contractions and two families that showed stability of the enlarged fragment during transmission. In four clinically defined DM patients we were unable to detect enlarged CTG repeats. Sequencing of each exon of the DM gene in two of these patients failed to show a ny mutations. Our cases have important implications for genetic counse lling of DM families, highlighting both the diagnostic value of direct genomic analysis and its limitations.