Dataset Information

Time Course of Disease Progression of PRPF31-mediated Retinitis Pigmentosa.

ABSTRACT: 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 to 77 years (mean 47 years), 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, without apparent relationship to specific variant. Two adults (aged 42 and 77 years) 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 < .001, 95% confidence interval [CI] 5.6-10.6), cone electroretinogram amplitude declined exponentially at a rate of 7.3% per year of disease duration (P < .001, 95% CI 5.4-9.1), and ellipsoid zone area declined exponentially at a rate of 5.4% per year of disease duration (P < .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.

SUBMITTER: Kiser K

PROVIDER: S-EPMC6481169 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Time Course of Disease Progression of PRPF31-mediated Retinitis Pigmentosa.

Kiser Kelly K Webb-Jones Kaylie D KD Bowne Sara J SJ Sullivan Lori S LS Daiger Stephen P SP Birch David G DG

American journal of ophthalmology 20181221

<h4>Purpose</h4>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.<h4>Design</h4>Cross-sectional with retrospective review.<h4>Methods</h4>A total of 26 patients with RP and 5 asymptomatic individuals, all ...[more]

PMID: 30582903

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Project description:ImportanceWhile oral vitamin A supplementation is considered to potentially slow loss of retinal function in adults with retinitis pigmentosa and normal liver function, little data from children with this disease are available.ObjectiveTo compare disease courses in children with retinitis pigmentosa taking or not taking vitamin A supplementation.Design, setting, and participantsRetrospective, nonrandomized comparison of vitamin A and control cohorts followed up for a mean of 4 to 5 years by the Electroretinography Service of the Massachusetts Eye and Ear Infirmary. The study included children with different genetic types of typical retinitis pigmentosa: 55 taking vitamin A and 25 not taking vitamin A. The dates for patient evaluations ranged from June 1976 to July 2016, and the data analysis occurred in October 2016.InterventionsAge-adjusted dose of oral vitamin A palmitate (≤15 000 IU/d).Main outcomes and measuresMean exponential rates of change of full-field cone electroretinogram amplitude to 30-Hz flashes estimated by repeated-measures longitudinal regression without and with adjusting for potential confounders.ResultsOf the 55 children in the vitamin A cohort, 38 (69%) were male; the mean [SD] age was 9.1 [1.9] years; and 48 (87%) were white , 6 (11%) were Asian, and 1 (2%) was black. Of the 25 members of the control cohort, 19 (76%) were male; the mean [SD] age was 9.2 [1.7] years; and 25 (100%) were white. The estimated mean rates of change with the unadjusted model were -0.0713 loge unit/y (-6.9% per year) for the vitamin A cohort and -0.1419 loge unit per year (-13.2% per year) for the control cohort (difference, 0.0706 loge unit per year; 95% CI for the difference, 0.0149-0.1263 loge unit per year; P = .01). The adjusted model confirmed a slower mean rate of decline in the vitamin A cohort (difference, 0.0771 loge-unit per year; 95% CI for the difference, 0.0191-0.1350 loge-unit per year; P = .009). With respect to ocular safety, the mean exponential rates of change of visual field area and visual acuity and the incidences of falling to a visual field diameter of 20° or less or a visual acuity of 20/200 or less in at least 1 eye did not differ by cohort.Conclusions and relevanceA vitamin A palmitate supplement was associated with a slower loss of cone electroretinogram amplitude in children with retinitis pigmentosa. Although the relatively small-sample, retrospective, nonrandomized design does not allow a test of causation and is subject to possible biases, these findings support consideration of an age-adjusted dose of vitamin A in the management of most children with the common forms of retinitis pigmentosa.

Dataset Information

Time Course of Disease Progression of PRPF31-mediated Retinitis Pigmentosa.

Publications

Time Course of Disease Progression of PRPF31-mediated Retinitis Pigmentosa.

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