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.
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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.)
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Chemical References |
- Ornithine-Oxo-Acid Transaminase
- Pyridoxine
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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)
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