NA06330
DNA from Fibroblast
Description:
GYRATE ATROPHY OF CHOROID AND RETINA; GACR
ORNITHINE AMINOTRANSFERASE; OAT
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases
Disorders of the Urea Cycle |
| Class |
Disorders of Amino Acid Metabolism |
| Quantity |
0.050mg |
| Quantitation Method |
Please see our FAQ |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Sample Source
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DNA from Fibroblast
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Race
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White
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Ethnicity
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ITALIAN
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| Passage Frozen |
3 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME |
PCR analysis of DNA from this cell culture gave a negative result with a primer for Yq11, DYS227. |
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| ornithine aminotransferase |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 2.6.1.13; <5% activity. |
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| Gene |
OAT |
| Chromosomal Location |
10q26 |
| Allelic Variant 1 |
258870.0038; GYRATE ATROPHY WITH PYRIDOXINE-RESPONSIVE ORNITHINEMIA |
| Identified Mutation |
ALA226VAL; In 2 unrelated patients with gyrate atrophy of the choroid and retina, Michaud et al. (1995) found a missense mutation, A226V. One patient, who was a compound for A226V and for the premature termination allele R398X, showed a significant decrease in mean plasma ornithine levels following pyridoxine supplementation with a constant protein intake. In extracts from fibroblasts of a second gyrate atrophy patient homozygous for A226V and also from Chinese hamster ovary cells expressing an OAT cDNA containing A226V, Michaud et al. (1995) 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. |
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| Gene |
OAT |
| Chromosomal Location |
10q26 |
| Allelic Variant 2 |
258870.0038; GYRATE ATROPHY WITH PYRIDOXINE-RESPONSIVE ORNITHINEMIA |
| Identified Mutation |
ALA226VAL; In 2 unrelated patients with gyrate atrophy of the choroid and retina, Michaud et al. (1995) found a missense mutation, A226V. One patient, who was a compound for A226V and for the premature termination allele R398X, showed a significant decrease in mean plasma ornithine levels following pyridoxine supplementation with a constant protein intake. In extracts from fibroblasts of a second gyrate atrophy patient homozygous for A226V and also from Chinese hamster ovary cells expressing an OAT cDNA containing A226V, Michaud et al. (1995) 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. |
| Remarks |
Elevated serum & urine ornithine levels; progressive blindness; no sign of neurologic involvement; severe constrict of visual fields; flat ERG; neg family history; < 5% of norm ornithine aminotransferase act; unrespon in vitro to Vit B6; donor subject is homozygous for a C>T transition at nucleotide 677 (677C>T) in exon 7 of the OAT gene which converts alanine 226 (GCG) to valine (GTG) [Ala226Val (A226V)] |
| Balfoort BM, Pampalone G, Ruiter JPN, Denis SW, Brands MM, GACR Bird's Eye View Consortium MM, Timmer C, Wagenmakers MAEM, Wanders RJA, van Karnebeek CD, Cellini B, Houtkooper RH, Ferdinandusse S, Extending diagnostic practices in gyrate atrophy: Enzymatic characterization and the development of an in vitro pyridoxine responsiveness assay Molecular genetics and metabolism143:108542 2024 |
| PubMed ID: 39053126 |
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| Foltz LP, Clegg DO, Patient-derived induced pluripotent stem cells for modelling genetic retinal dystrophies Progress in retinal and eye research143:108542 2018 |
| PubMed ID: 30217765 |
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| Michaud J, Thompson GN, Brody LC, Steel G, Obie C, Fontaine G, Schappert K, Keith CG, Valle D, Mitchell GA, Pyridoxine-responsive gyrate atrophy of the choroid and retina: clinical and biochemical correlates of the mutation A226V. Am J Hum Genet56:616-22 1995 |
| PubMed ID: 7887415 |
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