FRENCH MYOTONIC-DYSTROPHY FAMILIES SHOW EXPANSION OF A CTG REPEAT IN COMPLETE LINKAGE DISEQUILIBRIUM WITH AN INTRAGENIC 1 KB INSERTION

The molecular basis of myotonic dystrophy (DM) has been characterised. All DM mutations characterised to date appear as an unstable elongati on of a fragment containing a tandem repeat of a CTG motif, which can be visualised in both EcoRI and BamHI digests. It has been shown that the fragment is polymorphic in the normal population. Another 1 kb ins ertion/deletion polymorphism located near the unstable CTG repeat regi on has been identified. The 1 kb insertion allele is present in all DM patients. These different polymorphic systems can be distinguished us ing cDNA25 and BamHI, because this enzyme cuts between the site of the 1 kb insertion and the CTG repeat. We thus haplotyped DM patients fro m 72 French families and clearly showed that all chromosomes (100%) wi th the DM mutation carried the 1 kb insertion as well. In addition to this association, we detected significant linkage disequilibrium betwe en the DM locus and D19S63 for which allelic frequencies were differen t from other European populations. Our results in the French DM popula tion are thus in agreement with the hypothesis that the CTG expansion occurred on one or a few ancestral chromosomes carrying the large 1 kb insertion allele.