Molecular basis of ornithine aminotransferase deficiency in B-6-responsive and -nonresponsive forms of gyrate atrophy

Journal Article · Wed Jun 01 00:00:00 EDT 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.11.3777· OSTI ID:5517806

Ramesh, V; McClatchey, A I; Ramesh, N; Benoit, L A; Berson, E L; Shih, V E; Gusella, J F ^[1]

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1. Harvard Medical School, Boston, MA (USA)

Gyrate atrophy (GA), a recessive eye disease involving progressive loss of vision due to chorioretinal degeneration, is associated with a deficiency of the mitochondrial enzyme ornithine aminotransferase with consequent hyperornithinemia. Genetic heterogeneity of GA has been suggested by the demonstration that administration of pyridoxine to increase the level of pyridoxal phosphate, a cofactor of OATase, reduces hyperornithinemia in a subset of patients. The authors have cloned and sequences cDNAs for OATase from two GA patients, one responsive and one nonresponsive to pyridoxine treatment. The respective cDNAs contained different single missense mutations, which were sufficient to eliminate OATase activity when each cDNA was tested in a eukaryotic expression system. However, like the enzyme in fibroblasts from the pyridoxine-responsive patient, OATase encoded by the corresponding cDNA from this individual showed a significant increase in activity when assayed in the presence of an increased pyridoxal phosphate concentration. These data firmly establish that both pyridoxine responsive and nonresponsive forms of GA result from mutations in the OATase structural gene. Moreover, they provide a molecular characterization of the primary lesion in a pyridoxine-responsive genetic disorder.

• OSTI ID: 5517806
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 85:11; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AMINOTRANSFERASES
GENE MUTATIONS
HEREDITARY DISEASES
ETIOLOGY
RECOMBINANT DNA
DNA SEQUENCING
DNA-CLONING
EYES
GENES
MITOCHONDRIA
PATIENTS
PYRIDOXINE
SENSE ORGANS DISEASES
AZINES
BODY
BODY AREAS
CELL CONSTITUENTS
CLONING
DISEASES
DNA
DNA HYBRIDIZATION
ENZYMES
FACE
HEAD
HETEROCYCLIC COMPOUNDS
HYBRIDIZATION
HYDROXY COMPOUNDS
MUTATIONS
NITROGEN TRANSFERASES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
PYRIDINES
SENSE ORGANS
STRUCTURAL CHEMICAL ANALYSIS
TRANSFERASES
VITAMIN B GROUP
VITAMINS
550201* - Biochemistry- Tracer Techniques