Discordant phenotypes in fraternal twins having an identical mutation in exon ORF15 of the RPGR gene

• Published in: Archives of ophthalmology (1960) Vol. 126; no. 3; p. 379
• Main Authors: Walia, Saloni, Fishman, Gerald A, Swaroop, Anand, Branham, Kari E H, Lindeman, Martin, Othman, Mohammad, Weleber, Richard G
• Format: Journal Article
• Language: English
• Published: United States 01.03.2008
• Subjects: Diseases in Twins - diagnosis; Diseases in Twins - genetics; Diseases in Twins - physiopathology; DNA Mutational Analysis; Electroretinography; Exons - genetics; Eye Proteins - genetics; Genetic Diseases, X-Linked - diagnosis; Genetic Diseases, X-Linked - genetics; Genetic Diseases, X-Linked - physiopathology; Humans; Male; Middle Aged; Mutation; Open Reading Frames - genetics; Pedigree; Phenotype; Photoreceptor Cells, Vertebrate - physiology; Retinitis Pigmentosa - diagnosis; Retinitis Pigmentosa - genetics; Retinitis Pigmentosa - physiopathology; Twins, Dizygotic - genetics; Visual Acuity; Visual Field Tests; Visual Fields
• ISSN: 0003-9950
• DOI: 10.1001/archophthalmol.2007.72

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. 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. 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). 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. 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.