title: Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene.
abstract: Hereditary progressive dystonia with marked diurnal fluctuation (HPD) (also known as dopa responsive dystonia) is a dystonia with onset in childhood that shows a marked response without any side effects to levodopa. Recently the gene for dopa responsive dystonia (DRD) was mapped to chromosome 14q. Here we report that GTP cyclohydrolase I is mapped to 14q22.1-q22.2. The identification of four independent mutations of the gene for GTP cyclohydrolase I in patients with HPD, as well as a marked decrease in the enzyme's activity in mononuclear blood cells, confirms that the GTP cyclohydrolase I gene is a causative gene for HPD/DRD. This is the first report of a causative gene for the inherited dystonias.
authors.affiliation: Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ichinose
authors.forename: T
authors.initials: T
authors.lastname: Ohye
authors.forename: E
authors.initials: E
authors.lastname: Takahashi
authors.forename: N
authors.initials: N
authors.lastname: Seki
authors.forename: T
authors.initials: T
authors.lastname: Hori
authors.forename: M
authors.initials: M
authors.lastname: Segawa
authors.forename: Y
authors.initials: Y
authors.lastname: Nomura
authors.forename: K
authors.initials: K
authors.lastname: Endo
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: S
authors.initials: S
authors.lastname: Tsuji
mesh_terms: D017668:Age of Onset; D001708:Biopterins / Q000096:biosynthesis; D001921:Brain / Q000201:enzymology; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D002940:Circadian Rhythm; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D004298:Dopamine / Q000096:biosynthesis; D004421:Dystonia / Q000145:classification / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D004926:Escherichia coli; D005260:Female; D006136:GTP Cyclohydrolase / Q000097:blood / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D006822:Hybrid Cells; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010375:Pedigree; D016133:Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D001708:Biopterins; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D006136:GTP Cyclohydrolase; D004298:Dopamine