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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Age of Onset
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Biopterins / biosynthesis
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Brain / enzymology
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Chromosome Mapping*
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Chromosomes, Human, Pair 14
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Circadian Rhythm
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Cloning, Molecular
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DNA Mutational Analysis
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Dopamine / biosynthesis
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Dystonia / classification
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Dystonia / drug therapy
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Dystonia / epidemiology
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Dystonia / genetics*
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Escherichia coli
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Female
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GTP Cyclohydrolase / blood
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GTP Cyclohydrolase / genetics*
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Heterozygote
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Humans
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Hybrid Cells
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Levodopa / therapeutic use
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Male
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Mutagenesis, Site-Directed
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Mutation*
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Nerve Tissue Proteins / metabolism
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Pedigree
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Polymerase Chain Reaction
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Sequence Alignment
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Sequence Homology, Amino Acid
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Species Specificity
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Tyrosine 3-Monooxygenase / metabolism
Substances
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Nerve Tissue Proteins
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Biopterins
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Levodopa
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Tyrosine 3-Monooxygenase
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GTP Cyclohydrolase
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Dopamine