title: Functional evidence implicating a novel TOR1A mutation in idiopathic, late-onset focal dystonia.
abstract: BACKGROUND
  TOR1A encodes a chaperone-like AAA-ATPase whose Delta GAG (Delta E) mutation is responsible for an early onset, generalised dystonia syndrome. Because of the established role of the TOR1A gene in heritable generalised dystonia (DYT1), a potential genetic contribution of TOR1A to the more prevalent and diverse presentations of late onset, focal dystonia has been suggested.
  
  
  RESULTS
  A novel TOR1A missense mutation (c.613T-->A, p.F205I) in a patient with late onset, focal dystonia is reported. The mutation occurs in a highly evolutionarily conserved region encoding the AAA-ATPase domain. Expression assays revealed that expression of F205I or Delta E, but not wildtype TOR1A, produced frequent intracellular inclusions.
  
  
  CONCLUSIONS
  A novel, rare TOR1A variant has been identified in an individual with late onset, focal dystonia and evidence provided that the mutation impairs TOR1A function. Together these findings raise the possibility that this novel TOR1A variant may contribute to the expression of dystonia. In light of these findings, a more comprehensive genetic effort is warranted to identify the role of this and other rare TOR1A variants in the expression of late onset, focal dystonia.
authors: Center for Translational Neuroscience, Box 2900, Research Dr., Duke University Medical Center, Durham, NC 27710, USA. nicole.calakos@duke.edu
authors: Nicole
authors: N
authors: Calakos
authors: Viren D
authors: VD
authors: Patel
authors: Melissa
authors: M
authors: Gottron
authors: Gaofeng
authors: G
authors: Wang
authors: Khan-Nhat
authors: KN
authors: Tran-Viet
authors: Danielle
authors: D
authors: Brewington
authors: John L
authors: JL
authors: Beyer
authors: David C
authors: DC
authors: Steffens
authors: Ranga R
authors: RR
authors: Krishnan
authors: Stephan
authors: S
authors: Züchner
mesh_terms: D017668:Age of Onset; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D002460:Cell Line; D020821:Dystonic Disorders / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D008875:Middle Aged; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*
chemical_list: D018832:Molecular Chaperones; C108175:TOR1A protein, human