OAT mutations and clinical features in two Japanese brothers with gyrate atrophy of the choroid and retina.

BACKGROUND: Gyrate atrophy (GA) of the choroid and retina is an extremely rare inherited chorioretinal dystrophy. Ornithine aminotransferase (OAT) gene mutations are identified in patients with GA. The purpose of this study was to report a novel deletion mutation of the OAT gene and describe clinical features of two brothers with GA in a Japanese family. METHODS: We performed ophthalmic examinations, including best-corrected visual acuity, slit-lamp biomicroscopy, dilated funduscopy, fundus autofluorescence imaging, optical coherence tomography, visual field testing, and full-field electroretinography (ERG). Serum ornithine concentrations and OAT activities were analyzed. Mutation screening of the OAT gene was performed using Sanger sequencing. RESULTS: Both brothers had compound heterozygous mutations (p.K169DfsX10 and p.R426X), one of which was novel. Their unaffected parents carried one of the mutations heterozygously. An arginine-restricted diet was started in the younger brother at the age of 2 years, while the diet was not initiated in the older brother until the age of 6 years. After more than 15 years of follow-up, the dietary treatment seemed to slow the progression of the chorioretinal lesions in the younger brother. However, when compared at the same age, the younger brother had more reduced ERG amplitudes and constricted visual fields than his older brother. CONCLUSIONS: We identified a novel frameshift mutation (p.K169DfsX10) in the OAT gene. While an early arginine-restricted dietary treatment suppressed the fundus changes of GA to some degree in the younger brother, the efficacy of suppressing the progression of visual function loss could not be clearly determined.