Clinical Correlation for Two Novel Mutations in the RPGR Gene for X-linked Retinitis Pigmentosa

Abstract

Abstract: : Purpose: X-linked Retinitis Pigmentosa (XLRP) is a hereditary retinal degeneration that leads to the early onset of night blindness with progressive loss of peripheral vision and eventual legal blindness in most patients in later decades of life. We describe the clinical manifestations of two novel mutations in the RPGR gene in 3 patients. Mutations in RPGR have been associated with XLRP (RP3) and X-linked cone-rod dystrophy (COD1). Methods: Snellen visual acuity, ocular alignment, color vision assessment, intraocular pressure measurements and cycloplegic or manifest refractions were preformed, followed by complete slit lamp bimicroscopy and dilated fundus examination, electroretinograms, and Goldmann visual fields. Family ophthalmic histories were noted. Appropriate informed consent was obtained and DNA was extracted from whole blood samples. Coding regions plus ORF15 were polymerase chain reaction (PCR) amplified with intronic primers specific for the 19 exons and ORF15 of the RPGR gene. The amplified exon fragments underwent mutation analysis by standard direct sequencing techniques. Results: Patient #1, age 12 years, had a best corrected visual acuity (BCVA) of 20/25-, with onset of visual symptoms in the first decade; he had a mild to moderate myopic error of refraction, and carried a novel mutation in RPGR Exon 4 (333_336dup4). Patient #2, age 19 years, had BCVA of 20/40-, with onset of symptoms at age 13 years and a high myopic refractive error. Patient #3 was 27 years old; his BCVA was 20/200 with onset of night blindness at age 4 years; he was moderately to highly myopic. Both patient #2 and #3 had a novel mutation in RPGR ORF15 (ORF15+483_484delGA). Fundus appearance was typical of classic retinitis pigmentosa in all patients. Electroretinographic tracings were severely reduced or non-recordable in all patients. Conclusion: There appears to be no significant difference in the clinical presentation between these two particular mutations in the RPGR gene that cause classic XLRP with myopia.

Keywords: mutations • retinal degenerations: hereditary • genetics