A de novo ADCY5 mutation causes early‐onset autosomal dominant chorea and dystonia

Autor: Philippe Damier, Mirjana Radosavljevic, Raphael Carapito, Ghada Alsaleh, Louise Ott, Marion Le Gentil, Meiggie Untrau, Seiamak Bahram, Bertrand Isidor, Pierre Jochem, Cédric Le Caignec, Albert David, Nicodème Paul
Rok vydání: 2014
Předmět:
Zdroj: Movement Disorders. 30:423-427
ISSN: 1531-8257
0885-3185
DOI: 10.1002/mds.26115
Popis: Importance Apart 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. 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; 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. © 2014 International Parkinson and Movement Disorder Society
Databáze: OpenAIRE
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