Thornton Charles A, Wang Eric, Carrell Ellie M
Department of Neurology, University of Rochester, Rochester 14642, NY, United States.
Department of Molecular Genetics & Microbiology, Center for NeuroGenetics, University of Florida, Gainesville, FL, United States.
Curr Opin Genet Dev. 2017 Jun;44:135-140. doi: 10.1016/j.gde.2017.03.007. Epub 2017 Apr 1.
Myotonic dystrophy (DM) is a dominantly-inherited genetic disorder affecting skeletal muscle, heart, brain, and other organs. DM type 1 is caused by expansion of a CTG triplet repeat in DMPK, whereas DM type 2 is caused by expansion of a CCTG tetramer repeat in CNBP. In both cases the DM mutations lead to expression of dominant-acting RNAs. Studies of RNA toxicity have now revealed novel mechanisms and new therapeutic targets. Preclinical data have suggested that RNA dominance is responsive to therapeutic intervention and that DM therapy can be approached at several different levels. Here we review recent efforts to alleviate RNA toxicity in DM.
强直性肌营养不良（DM）是一种常染色体显性遗传的疾病，会影响骨骼肌、心脏、大脑及其他器官。1型强直性肌营养不良是由DMPK基因中CTG三联体重复序列的扩增引起的，而2型强直性肌营养不良则是由CNBP基因中CCTG四联体重复序列的扩增引起的。在这两种情况下，DM突变都会导致显性作用RNA的表达。目前对RNA毒性的研究揭示了新的机制和新的治疗靶点。临床前数据表明，RNA显性对治疗干预有反应，并且可以在几个不同层面上进行DM治疗。在这里，我们综述了最近为减轻DM中RNA毒性所做的努力。
