Three Novel Mutations in the RPGR Gene in Three Japanese Families with X–linked Retinitis Pigmentosa.

Abstract

Abstract: : Purpose:To assess the frequency and kinds of mutations in the RPGR gene among Japanese patients with X–linked retinitis pigmentosa (XLRP), to characterize the clinical features of patients with pathogenic mutations in this gene. Methods: Mutation screening by direct sequencing was performed on 21 unrelated patients with XLRP. The clinical features were characterized by visual acuity, slit–lamp biomicroscopy, electroretinography, fluorescein angiography, and kinetic visual field testing. Results: Molecular genetic analyses disclosed that three novel mutations, g.ORF15+249delC, g.ORF15+199_200insT and g.ORF15+1199–1225del27bp/insT, in the RPGR gene were identified in 4 patients from 3 unrelated families with XLRP. These mutations caused the frameshift and premature termination. Two affected members associated the g.ORF15+249delC mutation had the night blindness, progressive constriction of the visual field, severe retinal degeneration and myopia. The obligate carrier with this mutation showed high myopia and chorioretinal atrophy in the posterior pole bilaterally. Conclusions: We estimate that the mutations in the RPGR gene, accounts for approximately 14% of Japanese patients with XLRP. All mutations, which we identified in this study, were within exon ORF15. These findings suggested that the exon ORF15 was also the mutational hot spot for Japanese patients with XLRP.

Keywords: candidate gene analysis • retinal degenerations: hereditary • mutations