Ranum Laura P W, Cooper Thomas A
Institute of Human Genetics and Department of Genetics, Cell Biology & Development, University of Minnesota, Minneapolis, Minnesota 55455, USA.
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).
1型强直性肌营养不良（DM1）由位于肌强直性肌营养不良蛋白激酶基因3'非翻译区的CTG重复扩增突变引起。与扩增的CUG重复序列相互作用的RNA结合蛋白的鉴定和表征，以及内含子中类似的转录但未翻译的CCTG重复扩增导致2型强直性肌营养不良（DM2）的发现，揭示了一种新型机制，即微卫星扩增突变通过RNA功能获得机制导致疾病。本综述讨论了DM1和DM2中的RNA发病机制，以及有证据表明类似机制可能在越来越多的显性非编码扩增疾病中起作用，包括脆性X震颤共济失调综合征（FXTAS）、8型脊髓小脑共济失调（SCA8）、SCA10、SCA12和2型亨廷顿病样疾病（HDL2）。
