An intragenic duplication in guanosine triphosphate cyclohydrolase-1 gene in a dopa-responsive dystonia family

Mov Disord. 2011 Apr;26(5):905-9. doi: 10.1002/mds.23593. Epub 2011 Feb 1.

Abstract

Background: Autosomal dominant dopa-responsive dystonia is commonly caused by mutations in the guanosine triphosphate cyclohydrolase-1 gene.

Methods: We report a British family that has been followed for more than 20 years in which no mutations were previously identified.

Results: Reanalysis of this pedigree detected a duplication of guanosine triphosphate cyclohydrolase-1 exon 2 in affected family members. mRNA analysis showed a mutant transcript with a tandem exon 2 duplication. Four family members developed dopa-responsive dystonia, with onset in their late teens, and subsequently developed restless leg syndrome and migraine.

Conclusions: This is the first report of an intragenic guanosine triphosphate cyclohydrolase-1 duplication in a dopa-responsive dystonia family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiparkinson Agents / adverse effects
  • Dystonia / chemically induced
  • Dystonia / genetics*
  • Family Health*
  • Female
  • GTP Cyclohydrolase / genetics*
  • Genes, Duplicate / genetics*
  • Genetic Testing / methods
  • Humans
  • Levodopa / adverse effects
  • Male
  • Young Adult

Substances

  • Antiparkinson Agents
  • Levodopa
  • GTP Cyclohydrolase