title: The GTP cyclohydrolase I gene in Russian families with dopa-responsive dystonia.
abstract: OBJECTIVE
  To search for mutations in the GTP cyclohydrolase I (GCH-I) gene in a set of Russian families with dopa-responsive dystonia (DRD).
  
  
  METHODS
  Six large families with 54 affected family members and 2 patients with sporadic DRD were examined. Mutation screening was performed using single-strand conformation polymorphism analysis followed by direct sequencing of the presumably mutated exons, in patients whose results showed a normal pattern on single-strand conformation polymorphism analysis, the entire coding region of the GCH-I gene was sequenced.
  
  
  RESULTS
  Three new heterozygote point mutations located within exons 1, 2, and 4 of the GCH-I gene were identified in 3 families with autosomal-dominant inheritance. All these mutations are predicted to cause amino acid changes in the highly conserved regions of the gene. In patients from 3 other families and in both patients with sporadic DRD, no alterations in the translated portion of the GCH-I gene were observed.
  
  
  CONCLUSIONS
  Mutations in the coding region of the GCH-I gene account for a significant fraction (up to half) of the patients with a typical clinical picture of DRD. None of the mutations in the GCH-I gene described so far were detected more than once, which precludes the possibility of creating simple DNA testing procedures for routine clinical practice.
authors.affiliation: Department of Neurogenetics, Institute of Neurology, Russian Academy of Medical Sciences, Moscow.
authors.forename: S N
authors.initials: SN
authors.lastname: Illarioshkin
authors.forename: E D
authors.initials: ED
authors.lastname: Markova
authors.forename: P A
authors.initials: PA
authors.lastname: Slominsky
authors.forename: N I
authors.initials: NI
authors.lastname: Miklina
authors.forename: S N
authors.initials: SN
authors.lastname: Popova
authors.forename: S A
authors.initials: SA
authors.lastname: Limborska
authors.forename: S
authors.initials: S
authors.lastname: Tsuji
authors.forename: I A
authors.initials: IA
authors.lastname: Ivanova-Smolenskaya
mesh_terms: D000595:Amino Acid Sequence; D004421:Dystonia / Q000188:drug therapy / Q000235:genetics*; D006136:GTP Cyclohydrolase / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D012426:Russia
chemical_list: D007980:Levodopa; D006136:GTP Cyclohydrolase