- Overview
- Retinitis pigmentosa
- Cone/cone-rod dystrophy
- Additional information
- Multimodal imaging
- References
Overview
Gene (OMIM No.) |
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Function of gene/protein |
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Clinical phenotype (OMIM phenotype no.) |
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Inheritance |
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Signs for X-linked RP | Male patients
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Signs for cone/cone-rod dystrophy |
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Signs for macular degeneration |
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Visual function | X-linked RP
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Systemic features | Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness:
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Key investigations |
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Molecular diagnosis | Next generation sequencing
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Management | OcularSystemic
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Therapies under research |
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Further information |
Additional information
Pathogenic variants in RPGR account for 70-80% of X-linked RP cases and approximately 10% of total RP cases overall.[4,15-17] There is considerable intrafamilial phenotypic variability where the same genotype can cause both cone-rod dystrophy and RP phenotypes in different members of the same family.[8]
The highly repetitive ORF15 exon is a mutation “hot-spot” where most reported cone/cone-rod dystrophy variants and more than 50% of XL-RP variants are located.[4,10] A genotype-phenotype relationship can be observed:
- Most cone/cone-rod dystrophy variants are located towards the 3’ end of the ORF15 exon while those causing RP are located towards the 5’ end[19-22]
- Some studies have observed that patients harbouring variants in ORF15 display a milder RP phenotype compared to those with variants in exons 1-14, while other studies have suggested the contrary[8,15,18,21,22]
Multimodal imaging
Retinitis pigmentosa


Cone dystrophy


Female carrier

References
- Megaw RD, Soares DC, Wright AF. RPGR: Its role in photoreceptor physiology, human disease, and future therapies. Exp Eye Res. 2015;138:32-41
- Kirschner R, Rosenberg T, Schultz-Heienbrok R, et al. RPGR transcription studies in mouse and human tissues reveal a retina-specific isoform that is disrupted in a patient with X-linked retinitis pigmentosa. Hum Mol Genet. 1999;8(8):1571-1578
- Hosch J, Lorenz B, Stieger K. RPGR: role in the photoreceptor cilium, human retinal disease, and gene therapy. Ophthalmic Genet. 2011;32(1):1-11
- Vervoort R, Lennon A, Bird AC, et al. Mutational hot spot within a new RPGR exon in X-linked retinitis pigmentosa. Nat Genet. 2000;25(4):462-466
- Kurata K, Hosono K, Hayashi T, et al. X-linked Retinitis Pigmentosa in Japan: Clinical and Genetic Findings in Male Patients and Female Carriers. Int J Mol Sci. 2019;20(6)
- Koenekoop RK, Loyer M, Hand CK, et al. Novel RPGR mutations with distinct retinitis pigmentosa phenotypes in French-Canadian families. Am J Ophthalmol. 2003;136(4):678-687
- Nguyen XT, Talib M, van Schooneveld MJ, et al. RPGR-Associated Dystrophies: Clinical, Genetic, and Histopathological Features. Int J Mol Sci. 2020;21(3)
- Talib M, van Schooneveld MJ, Thiadens AA, et al. CLINICAL AND GENETIC CHARACTERISTICS OF MALE PATIENTS WITH RPGR-ASSOCIATED RETINAL DYSTROPHIES: A Long-Term Follow-up Study. Retina. 2019;39(6):1186-1199
- Talib M, van Schooneveld MJ, Van Cauwenbergh C, et al. The Spectrum of Structural and Functional Abnormalities in Female Carriers of Pathogenic Variants in the RPGR Gene. Invest Ophthalmol Vis Sci. 2018;59(10):4123-4133
- Tee JJ, Smith AJ, Hardcastle AJ, Michaelides M. RPGR-associated retinopathy: clinical features, molecular genetics, animal models and therapeutic options. Br J Ophthalmol. 2016;100(8):1022-1027
- Comander J, Weigel-DiFranco C, Sandberg MA, Berson EL. Visual Function in Carriers of X-Linked Retinitis Pigmentosa. Ophthalmology. 2015;122(9):1899-1906
- Moore A, Escudier E, Roger G, et al. RPGR is mutated in patients with a complex X linked phenotype combining primary ciliary dyskinesia and retinitis pigmentosa. J Med Genet. 2006;43(4):326-333
- Iannaccone A, Breuer DK, Wang XF, et al. Clinical and immunohistochemical evidence for an X linked retinitis pigmentosa syndrome with recurrent infections and hearing loss in association with an RPGR mutation. J Med Genet. 2003;40(11):e118
- Birch DG, Locke KG, Wen Y, Locke KI, Hoffman DR, Hood DC. Spectral-domain optical coherence tomography measures of outer segment layer progression in patients with X-linked retinitis pigmentosa. JAMA Ophthalmol. 2013;131(9):1143-1150
- Sharon D, Sandberg MA, Rabe VW, Stillberger M, Dryja TP, Berson EL. RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa. Am J Hum Genet. 2003;73(5):1131-1146
- Shu X, Black GC, Rice JM, et al. RPGR mutation analysis and disease: an update. Hum Mutat. 2007;28(4):322-328
- Pelletier V, Jambou M, Delphin N, et al. Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: genotype-phenotype correlations and impact on genetic counseling. Hum Mutat. 2007;28(1):81-91
- Fahim AT, Bowne SJ, Sullivan LS, et al. Allelic heterogeneity and genetic modifier loci contribute to clinical variation in males with X-linked retinitis pigmentosa due to RPGR mutations. PLoS One. 2011;6(8):e23021
- Ebenezer ND, Michaelides M, Jenkins SA, et al. Identification of novel RPGR ORF15 mutations in X-linked progressive cone-rod dystrophy (XLCORD) families. Invest Ophthalmol Vis Sci. 2005;46(6):1891-1898
- Demirci FY, Rigatti BW, Wen G, et al. X-linked cone-rod dystrophy (locus COD1): identification of mutations in RPGR exon ORF15. Am J Hum Genet. 2002;70(4):1049-1053
- Yang L, Yin X, Feng L, et al. Novel mutations of RPGR in Chinese retinitis pigmentosa patients and the genotype-phenotype correlation. PLoS One. 2014;9(1):e85752
- Andréasson S, Breuer DK, Eksandh L, et al. Clinical studies of X-linked retinitis pigmentosa in three Swedish families with newly identified mutations in the RP2 and RPGR-ORF15 genes. Ophthalmic Genet. 2003;24(4):215-223