title: A de novo ADCY5 mutation causes early-onset autosomal dominant chorea and dystonia.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Plateforme GENOMAX, Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Carapito
authors.forename: Nicodème
authors.initials: N
authors.lastname: Paul
authors.forename: Meiggie
authors.initials: M
authors.lastname: Untrau
authors.forename: Marion
authors.initials: M
authors.lastname: Le Gentil
authors.forename: Louise
authors.initials: L
authors.lastname: Ott
authors.forename: Ghada
authors.initials: G
authors.lastname: Alsaleh
authors.forename: Pierre
authors.initials: P
authors.lastname: Jochem
authors.forename: Mirjana
authors.initials: M
authors.lastname: Radosavljevic
authors.forename: Cédric
authors.initials: C
authors.lastname: Le Caignec
authors.forename: Albert
authors.initials: A
authors.lastname: David
authors.forename: Philippe
authors.initials: P
authors.lastname: Damier
authors.forename: Bertrand
authors.initials: B
authors.lastname: Isidor
authors.forename: Seiamak
authors.initials: S
authors.lastname: Bahram
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002819:Chorea / Q000235:genetics*; D004252:DNA Mutational Analysis; D020821:Dystonic Disorders / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*
chemical_list: D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V
keywords: ADCY5; chorea associated with dystonia; exome