A De Novo Adcy5 Mutation Causes Early-Onset Autosomal Dominant Chorea And Dystonia
Movement Disorders(2015)
摘要
ImportanceApart from Huntington's disease, little is known of the genetics of autosomal dominant chorea associated with dystonia. Here we identify adenylate cyclase 5 (ADCY5) as a likely new causal gene for early-onset chorea and dystonia.ObservationsWhole exome sequencing in a three-generation family affected with autosomal dominant chorea associated with dystonia identified a single de novo mutationc.2088+1G>A in a 5' donor splice-site of ADCY5segregating with the disease. This mutation seeming leads to RNA instability and therefore ADCY5 haploinsufficiency.Conclusions and RelevanceOur finding confirms the genetic/clinical heterogeneity of the disorder; corroborated by previous identification of ADCY5 mutations in one family with dyskinesia-facial myokymia and in two unrelated sporadic cases of paxoysmal choreic/dystonia-facial myokymia; ADCY5's high expression in the striatum and movement disorders in ADCY5-deficient mice. Hence ADCY5 genetic analyses may be relevant in the diagnostic workup of unexplained early-onset hyperkinetic movement disorders. (c) 2014 International Parkinson and Movement Disorder Society
更多查看译文
关键词
chorea associated with dystonia, ADCY5, exome
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要