title: Clinical similarities of hereditary progressive/dopa responsive dystonia caused by different types of mutations in the GTP cyclohydrolase I gene.
abstract: OBJECTIVE
  Hereditary progressive dystonia with pronounced diurnal fluctuation [(HPD)/dopa responsive dystonia (DRD)] is a childhood onset dystonia which responds to levodopa. Various clinical signs and symptoms of HPD/DRD have been recognised to date. Mutations in the GTP cyclohydrolase I (GTP-CH-I) gene were recently identified as the cause of HPD/ DRD. In the present study, the GTP-CH-I gene and the clinical features of eight HPD/DRD patients from six families were analysed to determine the correlations between clinical expression and the mutations in the GTP-CH-I gene.
  
  
  METHODS
  The exons, exon-intron junctions, and an indispensable part of the 5' flanking region of the GTP-CH-I gene were sequenced in the eight clinically diagnosed patients with HPD/DRD and their asymptomatic parents.
  
  
  RESULTS
  Three independent mutations in the GTP-CH-I gene were found in three patients. One of the patients and her asymptomatic mother were heterozygous for a novel mutation at the initiation codon. The three patients with dissimilar GTP-CH-I mutations exhibited similar clinical features. The other five patients with normal sequences presented several features not manifested by the three patients with the mutations. No mutation was found in the 5' flanking region of any patients or their parents.
  
  
  CONCLUSIONS
  A novel initiation codon mutation was found in a Japanese patient with HPD/DRD. The clinical manifestations common to the patients with HPD/ DRD with a mutated GTP-CH-I gene were also identified. Although focal manifestations of HPD/DRD associated with the mutations of this gene will be broadened, it is inferred that these clinical features are fundamental to HPD/DRD caused by mutations in this gene.
authors.affiliation: Department of Medical Genetics, Nara Medical University, Kashihara, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tamaru
authors.forename: M
authors.initials: M
authors.lastname: Hirano
authors.forename: H
authors.initials: H
authors.lastname: Ito
authors.forename: J
authors.initials: J
authors.lastname: Kawamura
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
authors.forename: T
authors.initials: T
authors.lastname: Imai
authors.forename: S
authors.initials: S
authors.lastname: Ueno
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D002940:Circadian Rhythm; D004247:DNA / Q000032:analysis*; D018450:Disease Progression; D015259:Dopamine Agents / Q000627:therapeutic use*; D005091:Exons / Q000235:genetics; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D006580:Genetic Carrier Screening; D015417:Hereditary Sensory and Motor Neuropathy / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007564:Japan; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA
chemical_list: D015259:Dopamine Agents; D007980:Levodopa; D004247:DNA; D006136:GTP Cyclohydrolase