Myotonic dystrophy: molecular analysis of Israeli patients

Myotonic dystrophy (DM) is an autosomal dominant, multisystem disorder and the most common adult form of muscular dystrophy. The age of onset and degree of severity of DM is highly variable. The biochemical defect in DM is unknown. DM was the first autosomal disorder to be localised by genetic linkage to protein markers (Lu, Se, C3), and assigned to chromosome 19. Linkage studies in DM families using RFLPs as polymorphic markers refined the mapping position to 19q13.1-13.2 distal to the BCL3, apoCII, CKM and ERCCI genes. Based on the linkage data, healthy individuals from DM families request a pre-symptomatic test. The information is of use in planning their family, if at high risk they can choose to have prenatal diagnosis. We have studied ten unrelated DM families by linkage analysis. The DNA probes to detect the various RFLPS were either from the vicinity of BCL3, ApoCII, CKMM and ECCRI genes or anonymous DNA probes. Linkage analysis in the DM families enabled us to determine the carrier status of healthy individuals and to perform prenatal diagnosis at a confidence of > 99%. In two families the DM diagnosis was in doubt and we did not include them in the combined analysis. Linkage disequilibrium was noted with two RFLPs pDIO/Pst1 and p37.1/BamH1. Both DNA probes were isolated by Shaw and his group in Cardiff. In six out of eight families, the DM chromosome was associated with allele 3 of pDIO/Pst1 and allele 1 of p37.1/BamH1.(ABSTRACT TRUNCATED AT 250 WORDS)