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

L. C. Brody, G. A. Mitchell, C. Obie, J. Michaud, G. Steel, G. Fontaine, M. F. Robert, I. Sipila, M. Kaiser-Kupfer, D. Valle

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


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-aminotransferase 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.

Original languageEnglish (US)
Pages (from-to)3302-3307
Number of pages6
JournalJournal of Biological Chemistry
Issue number5
StatePublished - 1992

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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