title: Combined occurrence of a novel TOR1A and a THAP1 mutation in primary dystonia.
abstract: BACKGROUND
  The ΔGAG deletion of the TOR1A gene (DYT1) is responsible for DYT1 dystonia. However, no other TOR1A mutation has been reported in the Chinese population.
  
  
  METHODS
  Two hundred one dystonia patients without the ΔGAG deletion were screened for other mutations in TOR1A. Gene function changes were analyzed by subcellular distribution and luciferase reporter assay.
  
  
  RESULTS
  A novel TOR1A mutation (c.581A>T, p.Asp194Val) was found in a patient with early-onset segmental dystonia harboring a THAP1 mutation (c.539T>C, p.Leu180Ser). Overexpression of mutant TOR1A Asp194Val protein induces inclusion formation in SK-N-AS cell lines, and the repressive activity of the mutant THAP1 Leu180Ser protein on TOR1A gene expression is decreased compared with wild-type THAP1.
  
  
  CONCLUSIONS
  This is the first report about a dystonia patient harboring two distinct dystonia gene mutations. Functional analysis indicated a potential additive effect of these two mutations, which might provoke the occurrence of dystonic symptoms in this patient.
authors.affiliation: Department of Medical Genetics, University of Tuebingen, 72076, Germany; Department of Neurology, the First Hospital of Jilin University, Changchun, PR China.
authors.forename: Fu-Bo
authors.initials: FB
authors.lastname: Cheng
authors.forename: Jia-Chun
authors.initials: JC
authors.lastname: Feng
authors.forename: Ling-Yan
authors.initials: LY
authors.lastname: Ma
authors.forename: Jing
authors.initials: J
authors.lastname: Miao
authors.forename: Thomas
authors.initials: T
authors.lastname: Ott
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Wan
authors.forename: Kathrin
authors.initials: K
authors.lastname: Grundmann
mesh_terms: D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D044466:Asian People; D001224:Aspartic Acid / Q000235:genetics; D045744:Cell Line, Tumor; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020821:Dystonic Disorders / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics*; D009447:Neuroblastoma / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014633:Valine / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C474080:THAP1 protein, human; C108175:TOR1A protein, human; D001224:Aspartic Acid; D014633:Valine
keywords: DYT1/TOR1A mutation; DYT6/THAP1 mutation; dual luciferase assay; primary dystonia; subcellular distribution