RNA-mediated neuromuscular disorders

Annu Rev Neurosci. 2006;29:259-77. doi: 10.1146/annurev.neuro.29.051605.113014.


Myotonic dystrophy type 1 (DM1) is caused by a CTG expansion mutation located in the 3' untranslated portion of the dystrophica myotonin protein kinase gene. The identification and characterization of RNA-binding proteins that interact with expanded CUG repeats and the discovery that a similar transcribed but untranslated CCTG expansion in an intron causes myotonic dystrophy type 2 (DM2) have uncovered a new type of mechanism in which microsatellite expansion mutations cause disease through an RNA gain-of-function mechanism. This review discusses RNA pathogenesis in DM1 and DM2 and evidence that similar mechanisms may play a role in a growing number of dominant noncoding expansion disorders, including fragile X tremor ataxia syndrome (FXTAS), spinocerebellar ataxia type 8 (SCA8), SCA10, SCA12, and Huntington's disease-like 2 (HDL2).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Genes, Dominant
  • Humans
  • Myotonic Dystrophy / genetics
  • Myotonic Dystrophy / metabolism
  • Neuromuscular Diseases / classification
  • Neuromuscular Diseases / genetics*
  • Neuromuscular Diseases / metabolism*
  • RNA / metabolism*
  • RNA-Binding Proteins / metabolism
  • Spinocerebellar Ataxias / genetics
  • Spinocerebellar Ataxias / metabolism
  • Trinucleotide Repeat Expansion / genetics*


  • RNA-Binding Proteins
  • RNA