TY - JOUR
T1 - Ornithine δ-aminotransferase mutations in gyrate atrophy
T2 - Allelic heterogeneity and functional consequences
AU - Brody, Lawrence C.
AU - Mitchell, Grant A.
AU - Obie, Cassandra
AU - Michaud, Jacques
AU - Steel, Gary
AU - Fontaine, Gisèle
AU - Robert, Marie France
AU - Sipila, Ilkka
AU - Kaiser-Kupfer, Muriel
AU - Valle, David
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1992/2/15
Y1 - 1992/2/15
N2 - Ornithine δ-aminotransferase is a nuclear-encoded mitochondrial matrix enzyme which catalyzes the reversible interconversion of ornithine and α-ketoglutarate to glutamate semialdehyde and glutamate. Inherited deficiency of ornithine δ-aminotransferase results in ornithine accumulation and a characteristic chorioretinal degeneration, gyrate atrophy of the choroid and retina. We have surveyed the ornithine δ-aminotransferase genes of gyrate atrophy patients for mutations. Using a variety of techniques, we discovered and molecularly characterized 21 newly recognized ornithine δ-aminotransferase alleles. We determined the consequences of these and three previously described mutations on ornithine δ-amino-transferase mRNA, antigen, and enzyme activity in cultured fibroblasts. The majority (20/24) of these alleles produce normal amounts of normally sized ornithine δ-aminotransferase mRNA. By contrast, only 2/ 24 had normal amounts of ornithine δ-aminotransferase antigen. Reproducing these mutations by site-directed mutagenesis and expressing the mutant ornithine δ-aminotransferase in Chinese hamster ovary cells confirms that several of these mutations inactivate ornithine δ-aminotransferase and cause gyrate atrophy in these patients.
AB - Ornithine δ-aminotransferase is a nuclear-encoded mitochondrial matrix enzyme which catalyzes the reversible interconversion of ornithine and α-ketoglutarate to glutamate semialdehyde and glutamate. Inherited deficiency of ornithine δ-aminotransferase results in ornithine accumulation and a characteristic chorioretinal degeneration, gyrate atrophy of the choroid and retina. We have surveyed the ornithine δ-aminotransferase genes of gyrate atrophy patients for mutations. Using a variety of techniques, we discovered and molecularly characterized 21 newly recognized ornithine δ-aminotransferase alleles. We determined the consequences of these and three previously described mutations on ornithine δ-amino-transferase mRNA, antigen, and enzyme activity in cultured fibroblasts. The majority (20/24) of these alleles produce normal amounts of normally sized ornithine δ-aminotransferase mRNA. By contrast, only 2/ 24 had normal amounts of ornithine δ-aminotransferase antigen. Reproducing these mutations by site-directed mutagenesis and expressing the mutant ornithine δ-aminotransferase in Chinese hamster ovary cells confirms that several of these mutations inactivate ornithine δ-aminotransferase and cause gyrate atrophy in these patients.
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M3 - Article
C2 - 1737786
AN - SCOPUS:0026744704
SN - 0021-9258
VL - 267
SP - 3302
EP - 3307
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 5
ER -