Pyridoxine-responsive gyrate atrophy of the choroid and retina: clinical and biochemical correlates of the mutation A226V

Am J Hum Genet. 1995 Mar;56(3):616-22.

Abstract

We discovered the missense mutation, A226V, in the ornithine-delta-aminotransferase (OAT) genes of two unrelated patients with gyrate atrophy of the choroid and retina (GA). One patient, who was a compound for A226V and for the premature termination allele R398ter, showed a significant (P < .01) decrease in mean plasma ornithine levels, following pyridoxine supplementation with a constant protein intake: 826 +/- 128 microM (n = 5; no pyridoxine supplementation) versus 504 +/- 112 microM (n = 6; 500 mg pyridoxine/d) and 546 +/- 19 microM (n = 6; 1,000 mg pyridoxine/d). In extracts of fibroblasts from a second GA patient homozygous for A226V and from Chinese hamster ovary cells expressing an OAT-cDNA-containing A226V, we found that OAT activity increased from undetectable levels to approximately 10% of normal when the concentration of pyridoxal phosphate was increased from 50 to 600 microM. A226V is the fourth disease-causing pyridoxine-responsive human mutation to be reported.

Publication types

  • Case Reports
  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • CHO Cells
  • Cells, Cultured
  • Child
  • Cricetinae
  • Cricetulus
  • Exons
  • Female
  • Fibroblasts / enzymology
  • Gyrate Atrophy / drug therapy
  • Gyrate Atrophy / enzymology
  • Gyrate Atrophy / genetics*
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Ornithine-Oxo-Acid Transaminase / genetics
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Pyridoxine / therapeutic use*

Substances

  • Ornithine-Oxo-Acid Transaminase
  • Pyridoxine