This study describes the clinical, genetic, and histopathological features in patients with RPGR-associated retinal dystrophies. Nine male patients from eight unrelated families underwent a comprehensive ophthalmic examination. Additionally, the histopathology of the right eye from a patient with an end-stage cone-rod-dystrophy (CRD)/sector retinitis pigmentosa (RP) phenotype was examined. All RPGR mutations causing a CRD phenotype were situated in exon ORF15. The mean best-corrected visual acuity (BCVA, decimals) was 0.58 (standard deviation (SD)): 0.34; range: 0.05–1.13); and the mean spherical refractive error was −4.1 D (SD: 2.11; range: −1.38 to −8.19). Hyperautofluorescent rings were observed in six patients. Full-field electroretinography responses were absent in all patients. The visual field defects ranged from peripheral constriction to central islands. The mean macular sensitivity on microperimetry was 11.6 dB (SD: 7.8; range: 1.6–24.4) and correlated significantly with BCVA (r = 0.907; p = 0.001). A histological examination of the donor eye showed disruption of retinal topology and stratification, with a more severe loss found in the peripheral regions. Reactive gliosis was seen in the inner layers of all regions. Our study demonstrates the highly variable phenotype found in RPGR-associated retinal dystrophies. Therapies should be applied at the earliest signs of photoreceptor degeneration, prior to the remodeling of the inner retina.

Cone-rod dystrophy, Genotype-phenotype, Histopathology, Natural history, Retinal dystrophies, Retinitis pigmentosa, Retinitis Pigmentosa GTPase Regulator (RPGR),
International Journal of Molecular Sciences
Department of Pathology

Nguyen, X.-T.-A. (Xuan-Thanh-An), Talib, M. (Mays), Schooneveld, M.J, Brinks, J. (Joost), ten Brink, J.B, Florijn, R.J, … Boon, C.J.F. (2020). RPGR-associated dystrophies: Clinical, genetic, and histopathological features. International Journal of Molecular Sciences, 21(3). doi:10.3390/ijms21030835