title: Molecular genetics of hereditary dystonia--mutations in the GTP cyclohydrolase I gene.
abstract: We found that mutations of GTP cyclohydrolase I, the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin, which is the cofactor of dopamine-synthesizing tyrosine hydroxylase, cause dominantly inherited hereditary progressive dystonia with marked diurnal fluctuation (HPD, Segawa's disease) probably owing to the decrease of dopamine in the basal ganglia. These results indicate that tyrosine hydroxylase in the nigrostriatal dopamine neurons may be most sensitive to tetrahydrobiopterin deficiency causing dystonia.
authors.affiliation: Division of Molecular Genetics II Neurochemistry, School of Medicine Fujita Health University, Aicihi, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ichinose
authors.forename: T
authors.initials: T
authors.lastname: Nagatsu
mesh_terms: D002648:Child; D004421:Dystonia / Q000201:enzymology / Q000235:genetics*; D006136:GTP Cyclohydrolase / Q000172:deficiency / Q000235:genetics*; D005799:Genes, Dominant; D005808:Genes, Recessive; D006801:Humans; D009154:Mutation; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: D014446:Tyrosine 3-Monooxygenase; D006136:GTP Cyclohydrolase