Purpose: To describe the phenotype and clinical course of patients with RPGR-associated retinal dystrophies, and to identify genotype–phenotype correlations. Methods: A multicenter medical records review of 74 male patients with RPGR-associated retinal dystrophies. Results: Patients had retinitis pigmentosa (RP; n = 52; 70%), cone dystrophy (COD; n = 5; 7%), or cone-rod dystrophy (CORD; n = 17; 23%). The median follow-up time was 11.6 years (range 0–57.1). The median age at symptom onset was 5.0 years (range 0–14 years) for patients with RP and 23.0 years (range 0–60 years) for patients with COD/CORD. The probability of being blind (best-corrected visual acuity ,0.05) at the age of 40 was 20% and 55% in patients with RP and COD/CORD, respectively. RPGR-ORF15 mutations were associated with high myopia (P = 0.01), which led to a faster best-corrected visual acuity decline in patients with RP (P , 0.001) and COD/CORD (P = 0.03). Patients with RP with RPGR-ORF15 mutations had a faster visual field decline (P = 0.01) and thinner central retina (P = 0.03) than patients with mutations in exon 1 to 14. Conclusion: Based on best-corrected visual acuity survival probabilities, the intervention window for gene therapy for RPGR-associated retinal dystrophies is relatively broad in patients with RP. RPGR-ORF15 mutations were associated with COD/CORD and with a more severe phenotype in RP. High myopia is a risk factor for faster best-corrected visual acuity decline.

Additional Metadata
Keywords cone-rod dystrophy, inherited retinal dystrophy, natural history, phenotype, progression rate, retinitis pigmentosa.
Persistent URL dx.doi.org/10.1097/iae.0000000000002125, hdl.handle.net/1765/119421
Series VSNU Open Access deal
Journal Retina
Note Corresponding author affiliated to LUMC
Talib, M., van Schooneveld, M.J, Thiadens, A.A., Fiocco, M, Wijnholds, J, Florijn, R.J, … Boon, C.J.F. (2019). Clinical And Genetic Characteristics Of Male Patients With RPGR-Associated Retinal Dystrophies. Retina, 39(6), 1186–1199. doi:10.1097/iae.0000000000002125