Pyridoxine-responsive gyrate atrophy of the choroid and retina: clinical and biochemical correlates of the mutation A226V.
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.
Michaud
J
J
Service de génétique médicale, Hôpital Ste-Justine, Montréal, Québec, Canada.
Thompson
G N
GN
Brody
L C
LC
Steel
G
G
Obie
C
C
Fontaine
G
G
Schappert
K
K
Keith
C G
CG
Valle
D
D
Mitchell
G A
GA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002478:Cells, Cultured; D002648:Child; D006224:Cricetinae; D003412:Cricetulus; D005091:Exons; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D015799:Gyrate Atrophy / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009953:Ornithine-Oxo-Acid Transaminase / Q000235:genetics; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011736:Pyridoxine / Q000627:therapeutic use*
D009953:Ornithine-Oxo-Acid Transaminase; D011736:Pyridoxine