Mutant GTP cyclohydrolase I in autosomal dominant dystonia and recessive hyperphenylalaninemia

Neurology. 1999 Jan 1;52(1):182-4. doi: 10.1212/wnl.52.1.182.

Abstract

Guanosine 5'-triphosphate cyclohydrolase I (GCH) mutants (H144P and T186K) associated with dominant dopa-responsive dystonia were enzymatically inactive and inhibited the normal enzyme, suggesting that GCH activity in a heterozygote was <50% of control. The M211I mutant associated with recessive hyperphenylalaninemia was slightly active and had no inhibitory effects, so GCH activity in a heterozygote would be <50% of normal; therefore hyperphenylalaninemia would be evident only in homozygotes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Dystonia / enzymology
  • Dystonia / genetics*
  • Enzyme Activation
  • GTP Cyclohydrolase / genetics*
  • GTP Cyclohydrolase / metabolism
  • Gene Expression Regulation, Enzymologic
  • Genes, Dominant*
  • Genes, Recessive*
  • Humans
  • Mutation, Missense
  • Phenotype
  • Phenylalanine / blood*
  • Phenylalanine / genetics
  • RNA, Messenger / analysis
  • Transfection

Substances

  • RNA, Messenger
  • Phenylalanine
  • GTP Cyclohydrolase