Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene

Nat Genet. 1994 Nov;8(3):236-42. doi: 10.1038/ng1194-236.


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

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Biopterin / biosynthesis
  • Brain / enzymology
  • Chromosome Mapping*
  • Chromosomes, Human, Pair 14
  • Circadian Rhythm
  • Cloning, Molecular
  • DNA Mutational Analysis
  • Dopamine / biosynthesis
  • Dystonia / classification
  • Dystonia / drug therapy
  • Dystonia / epidemiology
  • Dystonia / genetics*
  • Escherichia coli
  • Female
  • GTP Cyclohydrolase / blood
  • GTP Cyclohydrolase / genetics*
  • Heterozygote
  • Humans
  • Hybrid Cells
  • Levodopa / therapeutic use
  • Male
  • Mutagenesis, Site-Directed
  • Mutation*
  • Nerve Tissue Proteins / metabolism
  • Pedigree
  • Polymerase Chain Reaction
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Tyrosine 3-Monooxygenase / metabolism


  • Nerve Tissue Proteins
  • Biopterin
  • Levodopa
  • Tyrosine 3-Monooxygenase
  • GTP Cyclohydrolase
  • Dopamine