title: A novel mutation in the GTP cyclohydrolase I gene associated with a broad range of clinical presentations in a family with autosomal dominant dopa-responsive dystonia.
abstract: We examined a large family of Ashkenazi Jewish origin with autosomal dominant dopa-responsive dystonia (DRD). Mutation analysis of the GTP cyclohydrolase I gene revealed in affected members a novel point mutation (a C/A change in exon 1) resulting in a threonine-to-lysine substitution at residue 94. The mutation was characterized by variable expressivity and was associated with either a 'classical' DRD phenotype or various atypical phenotypes, such as subtle transitory equinovarus postures of the feet or isolated hand tremor. This observation demonstrates the significance of the molecular testing in establishing the clinical diagnosis of DRD.
authors.affiliation: Department of Neurogenetics, Institute of Neurology, Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: E D
authors.initials: ED
authors.lastname: Markova
authors.forename: P A
authors.initials: PA
authors.lastname: Slominsky
authors.forename: S N
authors.initials: SN
authors.lastname: Illarioshkin
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: I A
authors.initials: IA
authors.lastname: Ivanova-Smolenskaya
mesh_terms: D000978:Antiparkinson Agents / Q000627:therapeutic use*; D002230:Carbidopa / Q000627:therapeutic use; D004247:DNA / Q000032:analysis / Q000235:genetics; D004421:Dystonia / Q000188:drug therapy* / Q000235:genetics*; D005091:Exons; D006136:GTP Cyclohydrolase / Q000235:genetics*; D005799:Genes, Dominant; D006801:Humans; D007585:Jews; D007980:Levodopa / Q000627:therapeutic use*; D017354:Point Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D004247:DNA; D006136:GTP Cyclohydrolase; D002230:Carbidopa