Time Course of Disease Progression of PRPF31-Mediated Retinitis Pigmentosa

PURPOSE: Variants in PRPF31, a splicing factor, are a common cause of autosomal dominant retinitis pigmentosa (RP). Deleterious variants are thought to cause disease by haploinsufficiency. In anticipation of upcoming replacement gene therapy trials, we present the phenotype and clinical progression of a large cohort of patients with PRPF31-mediated RP. DESIGN: Cross-sectional with retrospective review METHODS: A total of 26 patients with RP and 5 asymptomatic individuals, all with deleterious variants in PRPF31 (from 13 families), were selected from our database of patients followed longitudinally. Ages ranged from 9-77 years (mean 47 years old), with an average follow up time of 16 years. All patients underwent ophthalmic examination including psychophysical tests, electrophysiology, and imaging. All available records were reviewed retrospectively. Additionally, all patients were contacted, and all available patients (n=7) were examined in an additional prospective follow up visit. RESULTS: Age of onset ranged from 6 to 71 years of age, without apparent relationship to specific variant. Two adults (ages 42 and 77) and 3 teenaged children were found to harbor a mutation with no evidence of RP. In those with RP, visual field area (spot size III) declined exponentially at a rate of 8.1% per year of disease duration (p<0.001, 95% CI 5.6-10.6) , electroretinogram (ERG) cone amplitude declined exponentially at a rate of 7.3% per year of disease duration (p<0.001, 95% CI 5.4-9.1), and ellipsoid zone (EZ) area declined exponentially at a rate of 5.4% per year of disease duration (p<0.001, 95% CI 3.7-7.1). CONCLUSIONS: PRPF31-mediated retinitis pigmentosa is characterized by a variable age of onset. Once disease develops, it follows a predictable exponential time course.