title: Phenotype of non-c.907_909delGAG mutations in TOR1A: DYT1 dystonia revisited.
abstract: BACKGROUND
  In addition to the most frequent TOR1A/DYT1 mutation (c.907_909delGAG), a growing number of TOR1A sequence variants are found in dystonia patients. For most, functional characterization has demonstrated pathogenicity at different levels, implying that TOR1A genetic testing should not be limited to screening for c.907_909delGAG.
  
  
  METHODS
  We tested 461 Serbian patients with isolated or combined dystonia for changes in the TOR1A gene and performed a systematic literature review of the clinical characteristics of patients carrying TOR1A mutations other than c.907_909delGAG.
  
  
  RESULTS
  One likely pathogenic TOR1A mutation (c.385G>A, p.Val129Ile) was detected in an adult-onset cervical dystonia patient. This change is in proximity to the previously reported p.Glu121Lys mutation and predicted to decrease the stability of TOR1A-encoded protein TorsinA.
  
  
  CONCLUSIONS
  Our patient and three other reported carriers of non-c.907_909delGAG-mutations within the first three exons of TOR1A showed similar phenotypes of adult-onset focal or segmental cervical dystonia. This observation raises the possibility of genotype-phenotype correlations in DYT1 and indicates that the clinical spectrum of this type of dystonia might be broader then previous classic descriptions.
authors: Neurology Clinic CCS, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors: Valerija
authors: V
authors: Dobričić
authors: Neurology Clinic CCS, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors: Nikola
authors: N
authors: Kresojević
authors: Neurology Clinic CCS, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors: Milena
authors: M
authors: Žarković
authors: Neurology Clinic CCS, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors: Aleksandra
authors: A
authors: Tomić
authors: Neurology Clinic CCS, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors: Ana
authors: A
authors: Marjanović
authors: Institute for Neurogenetics, University of Lübeck, Lübeck, Germany.
authors: Ana
authors: A
authors: Westenberger
authors: Department for Genetic and Evolution, Faculty of Biology, University of Belgrade, Belgrade, Serbia.
authors: Dragana
authors: D
authors: Cvetković
authors: Neurology Clinic CCS, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors: Marina
authors: M
authors: Svetel
authors: Institute for Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors: Ivana
authors: I
authors: Novaković
authors: Neurology Clinic CCS, School of Medicine, University of Belgrade, Belgrade, Serbia. Electronic address: vladimir.s.kostic@gmail.com.
authors: Vladimir S
authors: VS
authors: Kostić
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D020821:Dystonic Disorders / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D055771:Serbia; D055815:Young Adult
chemical_list: D018832:Molecular Chaperones; C108175:TOR1A protein, human
keywords: Isolated dystonia; Mutation; TOR1A