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

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.

• Authors: J Michaud, G N Thompson, L C Brody, G Steel, C Obie, G Fontaine, K Schappert, C G Keith, D Valle, G A Mitchell
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 56 Issue 3 Pg. 616-22 (Mar 1995) ISSN: 0002-9297 [Print] United States
• PMID: 7887415 (Publication Type: Case Reports, Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ornithine-Oxo-Acid Transaminase
• Pyridoxine

Topics

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