RNA-mediated neuromuscular disorders.
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).
Ranum
Laura P W
LP
Institute of Human Genetics and Department of Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, Minnesota 55455, USA. ranum001@umn.edu
Cooper
Thomas A
TA
D000818:Animals; D005799:Genes, Dominant; D006801:Humans; D009223:Myotonic Dystrophy / Q000235:genetics / Q000378:metabolism; D009468:Neuromuscular Diseases / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D020754:Spinocerebellar Ataxias / Q000235:genetics / Q000378:metabolism; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
D016601:RNA-Binding Proteins; D012313:RNA