Pyridoxine-responsive gyrate atrophy of the choroid and retina: clinical and biochemical correlates of the mutation A226V
| Autor: | J, Michaud, G N, Thompson, L C, Brody, G, Steel, C, Obie, G, Fontaine, K, Schappert, C G, Keith, D, Valle, G A, Mitchell |
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| Rok vydání: | 1995 |
| Předmět: |
Base Sequence
Ornithine-Oxo-Acid Transaminase Molecular Sequence Data Pyridoxine CHO Cells Exons Fibroblasts Polymerase Chain Reaction Cricetulus Cricetinae Mutation Animals Gyrate Atrophy Humans Female Amino Acid Sequence Child Cells Cultured Polymorphism Single-Stranded Conformational Research Article |
| Zdroj: | American journal of human genetics. 56(3) |
| ISSN: | 0002-9297 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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