Myotonic dystrophy

Abstract

Myotonic dystrophy (DM) is the most common form of muscular dystrophy in adults, caused by unstable genomic expansions of simple tandem repeats. Myotonic dystrophy type 1 (DM1) results from expansion of a CTG repeat in the 30 untranslated region of DMPK. In myotonic dystrophy type 2 (DM2), the expanded repeat is a CCTG tetramer in intron 1 of CNBP/ZNF9. The mRNA transcripts containing expanded repeats form ribonuclear inclusions, thereby retained in the nucleus. The mutant RNA gives rise to a toxic gain of function by perturbing splicing factors, resulting in misregulation of alternative pre-mRNA splicing that may underlie the multisystemic symptoms of DM. Although no curative treatment exists, recent advances in basic and translational research and pharmacological approaches provide clues for therapeutic intervention in DM. In this review, we describe the RNA-dominant mechanism in DM and summarize potential therapeutic approaches that address RNA toxicity and current progress toward translational research.