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Saloni Walia, MD; Gerald A. Fishman, MD; Anand Swaroop, PhD; Kari E. H. Branham, MS; Martin Lindeman, COMT; Mohammad Othman, PhD; Richard G. Weleber, MD

Arch Ophthalmol. 2008;126(3):379-384.

Objective  To report discordant phenotypes, resulting from the same mutation in exon ORF15 (GenBank AF286472) of the retinitis pigmentosa GTPase regulator gene (RPGR) (GenBank U57629), in 2 presumed dizygotic twin brothers with X-linked retinal disease.

Methods  The 2 brothers underwent complete ophthalmic examination that included best-corrected visual acuity, slitlamp biomicroscopy, and detailed fundus examination. Visual field recording using Goldmann kinetic perimetry and a full-field electroretinogram were also obtained in both patients. Mutational screening was performed for RPGR because of an X-linked pattern of inheritance indicated by pedigree analysis.

Results  One brother had a phenotypic expression of cone-rod dystrophy, while the other exhibited X-linked retinitis pigmentosa. A 1-nucleotide deletion was identified in the 3' region of exon ORF15 of RPGR (ORF15 + 1339delA).

Conclusions  An identical mutation in RPGR-ORF15 manifested distinct clinical phenotypes in individuals of the same family. Our data provide strong evidence in support of additional modifier genes that can produce diverse disease phenotypes in patients with RPGR mutations.

Clinical Relevance  The clinical observation of different retinal phenotypes in a family with the same mutation in exon ORF15 of RPGR implicates the potential importance of modifier genes for the phenotypic expression of this form of X-linked retinal disease.

Author Affiliations: Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago (Drs Walia and Fishman and Mr Lindeman), Departments of Ophthalmology & Visual Sciences and Human Genetics, University of Michigan, Ann Arbor (Drs Swaroop and Othman and Ms Branham); and Casey Eye Institute, Oregon Health & Science University, Portland (Dr Weleber).

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