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

J. Michaud, G. N. Thompson, L. C. Brody, G. Steel, C. Obie, G. Fontaine, K. Schappert, C. G. Keith, D. Valle, G. A. Mitchell

Research output: Contribution to journalArticlepeer-review

Abstract

We discovered the missense mutation, A226V, in the ornithine-δ- 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 μM (4 = 5; no pyridoxine supplementation) versus 504 ± 112 μM (n = 6; 500 mg pyridoxine/d) and 546 ± 19 μM (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 ~10% of normal when the concentration of pyridoxal phosphate was increased from 50 to 600 μM. A226V is the fourth disease-causing pyridoxine-responsive human mutation to be reported.

Original languageEnglish (US)
Pages (from-to)616-622
Number of pages7
JournalAmerican journal of human genetics
Volume56
Issue number3
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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