Heterogeneity and uniqueness of ornithine aminotransferase mutations found in Japanese gyrate atrophy patients

PURPOSE: To identify mutations in ornithine aminotransferase (OAT) in seven Japanese families with gyrate atrophy (GA), an autosomal recessive chorioretinal degeneration of the eye caused by a generalized biochemical deficiency in OAT; mutations in the OAT gene have shown a high degree of molecular heterogeneity. METHODS: DNA was prepared from patients' fibroblasts and analyzed by polymerase-chain-reaction amplification of the OAT gene sequence, denaturing gradient gel electrophoresis, and direct sequencing for identification of the mutations. RESULTS: Eight different mutations were identified in seven unrelated Japanese GA patients with hyperornithinemia, confirming the high genetic heterogeneity of this disease. Five of these mutations were new, including one causing a pyridoxine-responsive disease, and all eight mutations have been found only in Japanese GA patients. Consistent with some similarity between the Japanese and Finnish populations in genetic isolation and homogeneity, there was a preponderance of homozygous mutations (five out of seven patients) as was previously reported for 16 Finnish GA pedigrees. CONCLUSION: The eight Japanese OAT mutations represent a group of heterogenous mutations unique to a specific population pool.