부산대학교 도서관

IMPORTANCE:: Apart from Huntingtonʼs 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. OBSERVATIONS:: Whole exome sequencing in a three-generation family affected with autosomal dominant chorea associated with dystonia identified a single de novo mutation—c.2088+1G>A in a 5′ donor splice-site of ADCY5—segregating with the disease. This mutation seeming leads to RNA instability and therefore ADCY5 haploinsufficiency. CONCLUSIONS AND RELEVANCE:: Our 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; ADCY5ʼs 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. © 2014 International Parkinson and Movement Disorder Society