Myotonic Dystrophy Mutation: An Unstable CTG Repeat in the 3′ Untranslated Region of the Gene

• Published in: Science (American Association for the Advancement of Science) 1992-03, Vol.255 (5049), p.1253-1255
• Main Authors: Mahadevan, Mani, Tsilfidis, Catherine, Sabourin, Luc, Shutler, Gary, Amemiya, Chris, Jansen, Gert, Neville, Catherine, Narang, Monica, Barceló, Juana, O'Hoy, Kim, Leblond, Suzanne, Earle-Macdonald, Jane, De Jong, Pieter J., Wieringa, Bé, Korneluk, Robert G.
• Format: Article
• Language: English
• Subjects: Alleles; Analysis; Anatomy; Base Sequence; Biological and medical sciences; Blotting, Southern; Chromosomes, Human, Pair 19; Codon; Complementary DNA; Deoxyribonuclease EcoRI; Diseases of striated muscles. Neuromuscular diseases; DNA; DNA - chemistry; DNA probes; Exons; Gels; genes; Genetic aspects; Genetic disorders; Genetic mutation; Genetics; Genomics; Humans; Medical sciences; Molecular Sequence Data; Muscular dystrophy; Mutation; Mutation (Biology); Myotonic dystrophy; Myotonic Dystrophy - genetics; Neurology; Nucleic Acid Hybridization; Nucleotide sequence; Polymerase Chain Reaction; Polymorphism, Genetic; Repetitive Sequences, Nucleic Acid; restriction fragment length polymorphism; Restriction Mapping
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1546325

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 3ḿ 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.