Myotonic dystrophies: An update on clinical aspects, genetic, pathology, and molecular pathomechanisms

Giovanni Meola, Rosanna Cardani

Research output: Contribution to journalArticlepeer-review

Abstract

Myotonic dystrophy (DM) is the most common adult muscular dystrophy, characterized by autosomal dominant progressive myopathy, myotonia and multiorgan involvement. To date two distinct forms caused by similar mutations have been identified. Myotonic dystrophy type 1 (DM1, Steinert's disease) is caused by a (CTG)n expansion in DMPK, while myotonic dystrophy type 2 (DM2) is caused by a (CCTG)n expansion in ZNF9/CNBP. When transcribed into CUG/CCUG-containing RNA, mutant transcripts aggregate as nuclear foci that sequester RNA-binding proteins, resulting in spliceopathy of downstream effector genes. However, it is now clear that additional pathogenic mechanism like changes in gene expression, protein translation and micro-RNA metabolism may also contribute to disease pathology. Despite clinical and genetic similarities, DM1 and DM2 are distinct disorders requiring different diagnostic and management strategies. This review is an update on the recent advances in the understanding of the molecular mechanisms behind myotonic dystrophies. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.

Original languageEnglish
Pages (from-to)594-606
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1852
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

Keywords

  • Clinical finding
  • Molecular mechanism
  • Muscle biopsy
  • Myotonic dystrophy type 1
  • Myotonic dystrophy type 2
  • Pathology

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Medicine(all)

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