Expansion of the CTG repeat region was found in 98% (253 of 258) of individuals with myotonic dystrophy, suggesting it is the primary cause of the disease.
Observational (n=258)
Identified that myotonic dystrophy is primarily caused by an unstable CTG trinucleotide repeat expansion, providing a genetic basis for the disease and the phenomenon of genetic anticipation.
Myotonic dystrophy (DM) is the most common inherited neuromuscular disease in adults, with a global incidence of 1 in 8000 individuals. DM is an autosomal dominant, multisystemic disorder characterized primarily by myotonia and progressive muscle weakness. Genomic and complementary DNA probes that map to a 10-kilobase Eco RI genomic fragment from human chromosome 19q13.3 have been used to detect a variable length polymorphism in individuals with DM. Increases in the size of the allele in patients with DM are now shown to be due to an increased number of trinucleotide CTG repeats in the 3' untranslated region of a DM candidate gene. An increase in the severity of the disease in successive generations (genetic anticipation) is accompanied by an increase in the number of trinucleotide repeats. Nearly all cases of DM (98 percent or 253 of 258 individuals) displayed expansion of the CTG repeat region. These results suggest that DM is primarily caused by mutations that generate an amplification of a specific CTG repeat.
Mahadevan et al. (1992) conducted an observational in Myotonic dystrophy (n=258). CTG repeat expansion in the 3' untranslated region of a DM candidate gene was evaluated on Presence of CTG repeat expansion. Expansion of the CTG repeat region was found in 98% (253 of 258) of individuals with myotonic dystrophy, suggesting it is the primary cause of the disease.