Identification of novel RPGR ORF15 mutations in X-linked progressive conerod dystrophy (XLCORD) families. Invest Ophthalmol Vis Sci 46

PURPOSE. To test the incidence of mutations in RPGR ORF15 in six families with X-linked progressive retinal degeneration (cone-rod dystrophy [XLCORD], macular or cone dystrophy) and to undertake a detailed phenotypic assessment of families in whom ORF15 mutations were identified. METHODS. To amplify and sequence ORF15 in its entirety, a cloning strategy was developed. Families with mutations in ORF15 underwent electrophysiological testing, color vision assessment, color fundus photography, and fundus autofluo-rescence (AF) imaging. RESULTS. Novel protein truncation mutations were identi-fied in two families. In family A, a 2-bp mutation was iden-tified in ORF15A1094C G1095T, predicted to result in a truncated protein (E364D/E365X). In family B, a G-to-T transversion (ORF151176GT) resulted in a nonsense mutation (G392X). Characteristics of phenotype in both families included progressive deterioration of central vi-sion and subsequently night vision, mild photophobia, and moderate to high myopia. Ophthalmoscopic abnormalities were generally confined to the macula. A parafoveal ring of increased AF was observed, and electrophysiological evi-dence of a greater generalized abnormality in cone than rod responses were consistent with a cone–rod dystrophy phe-notype. CONCLUSIONS. The cloning strategy for ORF15 facilitated com-prehensive sequence analysis in patients. Two families were identified with nonsense mutations, and clinical evaluation revealed them both to have a similar phenotype. The presence of a parafoveal ring of increased AF was an early indicator of affected status in these families. No disease-causing mutations in ORF15 were detected in four other families, suggesting that ORF15 mutations may not be the most common cause o