Natural history of PRPF31-associated retinopathy: multimodal imaging findings

Abstract

Purpose : PRPF31-associated retinopathy (RP11, OMIM: #600138) is a common form of autosomal dominant retinitis pigmentosa (adRP). RP11 exhibits extreme variation in phenotype, ranging from non-penetrance to severe early-onset RP. Herein, we report four patterns of RP11 natural history in seven unrelated families in a prospective cohort study.

Methods : Patients underwent complete ophthalmic examination, 10-2 microperimetry (MAIA), spectral-domain optical coherence tomography and fundus autofluorescence imaging at baseline and every 6 months thereafter. Main outcome measures included age of onset of symptoms, best-corrected visual acuity (BCVA), microperimetry mean sensitivity (MS), residual ellipsoid (EZ) span and hyperautofluorescent ring (HAR) area. Genotyping was performed using targeted next-generation sequencing and Sanger sequencing.

Results : PRPF31 mutation was found in 14 members. The four patterns of disease phenotype are: (A) childhood onset with rapid progression (Figure 1A), (B) adult-onset with rapid progression (Figure 1B), (C) adult-onset with slow progression (Figure 1C) and, (D) non-penetrance (Figure 1D). Patients in group A (n=4) revealed no or barely detectable EZ with a BCVA of 20/50 or worse and MS less than 2 dB by age 50 years (n=2) or counting fingers by age 80 years (n=2). Patients in group B (n=4) presented with EZ span reduced to 4000 µm by age 17 (n=1), 3000 µm by age 29 (n=1) and 1500 µm by early 60s (n=2). Group C (n=4) revealed either a mild asymptomatic phenotype (normal MS and large EZ and HAR) at age 18 (n=1) or residual EZ span greater than 3500 µm and MS 8–19 dB by age 34–63 (n=3). Two unaffected patients were assigned to group D. Two families revealed combinations of phenotypes across and within generations. All detected mutations are predicted to lead to a loss of PRPF31 function.

Conclusions : Our findings suggest disease expression may be related to the level of wild-type PRPF31 allele expression rather than the type of the mutation. Further in vitro studies correlating wild-type PRPF31 allele expression level with clinical manifestation are necessary.

This is a 2021 ARVO Annual Meeting abstract.

 

Figure 1. Examples of childhood-onset with rapid progression (A), adult-onset with rapid progression (B), adult-onset with slow progression (C) and non-penetrance (D) phenotypes in patients with RP11. EZ = ellipsoid zone; HAR = hyperautofluorescent ring; MS = mean sensitivity.