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Ornithine delta-aminotransferase mutations in gyrate atrophy. Allelic heterogeneity and functional consequences. 1992

L C Brody, and G A Mitchell, and C Obie, and J Michaud, and G Steel, and G Fontaine, and M F Robert, and I Sipila, and M Kaiser-Kupfer, and D Valle
Laboratory of Genetics, Howard Hughes Medical Institute, John Hopkins University School of Medicine, Baltimore, Maryland 21205.

Ornithine delta-aminotransferase is a nuclear-encoded mitochondrial matrix enzyme which catalyzes the reversible interconversion of ornithine and alpha-ketoglutarate to glutamate semialdehyde and glutamate. Inherited deficiency of ornithine delta-aminotransferase results in ornithine accumulation and a characteristic chorioretinal degeneration, gyrate atrophy of the choroid and retina. We have surveyed the ornithine delta-aminotransferase genes of gyrate atrophy patients for mutations. Using a variety of techniques, we discovered and molecularly characterized 21 newly recognized ornithine delta-aminotransferase alleles. We determined the consequences of these and three previously described mutations on ornithine delta-aminotransferase mRNA, antigen, and enzyme activity in cultured fibroblasts. The majority (20/24) of these alleles produce normal amounts of normally sized ornithine delta-aminotransferase mRNA. By contrast, only 2/24 had normal amounts of ornithine delta-aminotransferase antigen. Reproducing these mutations by site-directed mutagenesis and expressing the mutant ornithine delta-aminotransferase in Chinese hamster ovary cells confirms that several of these mutations inactivate ornithine delta-aminotransferase and cause gyrate atrophy in these patients.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009953 Ornithine-Oxo-Acid Transaminase A pyridoxal phosphate enzyme that catalyzes the formation of glutamate gamma-semialdehyde and an L-amino acid from L-ornithine and a 2-keto-acid. EC 2.6.1.13. Ornithine Aminotransferase,Ornithine Transaminase,L-Ornithine-2-Oxo-Acid Aminotransferase,L-Ornithine-2-Oxoglutarate Aminotransferase,Ornithine Ketoacid Aminotransferase,Ornithine-2-Ketoglutarate Aminotransferase,Ornithine-Keto-Acid-Transaminase,Ornithine-Ketoacid-Transaminase,Pyrroline-5-Carboxylate Synthase,Aminotransferase, L-Ornithine-2-Oxo-Acid,Aminotransferase, L-Ornithine-2-Oxoglutarate,Aminotransferase, Ornithine,Aminotransferase, Ornithine Ketoacid,Aminotransferase, Ornithine-2-Ketoglutarate,Ketoacid Aminotransferase, Ornithine,L Ornithine 2 Oxo Acid Aminotransferase,L Ornithine 2 Oxoglutarate Aminotransferase,Ornithine 2 Ketoglutarate Aminotransferase,Ornithine Keto Acid Transaminase,Ornithine Ketoacid Transaminase,Ornithine Oxo Acid Transaminase,Pyrroline 5 Carboxylate Synthase,Synthase, Pyrroline-5-Carboxylate,Transaminase, Ornithine,Transaminase, Ornithine-Oxo-Acid
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000483 Alleles Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product. Allelomorphs,Allele,Allelomorph
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein

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