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

Mov Disord. 2015 Mar;30(3):423-7. doi: 10.1002/mds.26115. Epub 2014 Dec 27.


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.

Keywords: ADCY5; chorea associated with dystonia; exome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Adenylyl Cyclases / genetics*
  • Adolescent
  • Adult
  • Chorea / genetics*
  • DNA Mutational Analysis
  • Dystonic Disorders / genetics*
  • Family Health*
  • Female
  • Humans
  • Male
  • Mutation / genetics*


  • Adenylyl Cyclases
  • adenylyl cyclase type V