Two previously unrecognized splicing mutations of GCH1 in Dopa-responsive dystonia: exon skipping and one base insertion

Neurogenetics. 1997 Sep;1(2):125-7. doi: 10.1007/s100480050018.

Abstract

We describe two previously unrecognized splice site mutations of GCH1 in Dopa responsive dystonia (DRD). Both mutations affect consensus splice acceptor (AG) sites. The first mutation is an A-->G transition at position -2 of intron 1 of GCH1. This mutation results in skipping of exon 2. Fusion of exons 1 and 3 causes a frame shift that generates a premature stop codon. The second mutation is an A-->G transition at position -2 of intron 2. The mutation generates a new splice acceptor site AG one base pair upstream of the wild-type splice site. This, together with a pyrimidine stretch upstream of the new splice site, renders this site functional and generates a transcript with the insertion of one base, i.e. the G of the wild-type splice site. This in turn causes a frame shift including the introduction of a premature stop codon. The two different mutations generate truncated GTP cyclohydrolase polypeptides.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Alternative Splicing / genetics*
  • Amino Acid Sequence
  • Antiparkinson Agents / therapeutic use*
  • Base Sequence
  • Child
  • Child, Preschool
  • DNA / chemistry
  • DNA / genetics
  • DNA Mutational Analysis
  • Dystonia / drug therapy
  • Dystonia / genetics*
  • Exons / genetics
  • Female
  • Follow-Up Studies
  • Frameshift Mutation
  • GTP Cyclohydrolase / genetics*
  • Humans
  • Levodopa / therapeutic use*
  • Mutation
  • Point Mutation
  • Polymorphism, Single-Stranded Conformational

Substances

  • Antiparkinson Agents
  • Levodopa
  • DNA
  • GTP Cyclohydrolase