Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene.
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.
Ichinose
H
H
Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan.
Ohye
T
T
Takahashi
E
E
Seki
N
N
Hori
T
T
Segawa
M
M
Nomura
Y
Y
Endo
K
K
Tanaka
H
H
Tsuji
S
S
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
D009419:Nerve Tissue Proteins; D001708:Biopterins; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D006136:GTP Cyclohydrolase; D004298:Dopamine