To describe the phenotype and clinical course of patients with RPGR-associated retinal dystrophies, and to identify genotype–phenotype correlations.
A multicenter medical records review of 74 male patients with RPGR-associated retinal dystrophies.
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.
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.
This study of the spectrum of RPGR-associated retinal dystrophies showed an association of RPGR-ORF15 mutations with higher myopia, with cone/cone-rod degeneration, and with a faster disease progression in retinitis pigmentosa, regarding visual acuity, visual field, and retinal thickness. High myopia leads to a significantly faster visual acuity decline.
*Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands;
†Department of Ophthalmology, Academic Medical Center, Amsterdam, the Netherlands;
‡Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands;
§Department of Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands;
¶Mathematical Institute, Leiden University, Leiden, the Netherlands;
**Department of Clinical Genetics, Academic Medical Center, Amsterdam, the Netherlands;
††Bartiméus, Diagnostic Centre for Complex Visual Disorders, Zeist, the Netherlands;
‡‡Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands;
§§Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland;
¶¶Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands;
***Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands;
†††Rotterdam Eye Hospital, Rotterdam, the Netherlands; and
‡‡‡The Netherlands Institute for Neuroscience (NIN-KNAW), Amsterdam, the Netherlands.
Reprint requests: Camiel J. F. Boon, MD, PhD, Department of Ophthalmology, Leiden University Medical Center, J3-S, Albinusdreef 2, 2333 ZA, Leiden, the Netherlands; e-mail: firstname.lastname@example.org
Curing Retinal Blindness Foundation (USA), Stichting Blindenhulp (the Netherlands), Janivo Stichting (the Netherlands).
None of the authors has any financial/conflicting interests to disclose.
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