Researchers at the Department of Ophthalmology, Copenhagen University Hospital – Rigshospitalet-Glostrup, Denmark, has reported a long-term follow-up study on the natural history of PRPF31-related retinitis pigmentosa (RP11) patients demonstrating the importance of differentiation between specific genotypes and charting the outcome measures over time. RP11 disease progression patterns may vary between genotypes and exact genotyping and natural history studies are necessary to investigate the specific genotype–phenotype relations. In their study, the natural-course of RP subtypes are useful and essential in planning rehabilitation and conduction of future prospective, and ultimately, possible treatment trials.
RP11 shows pathogenic variants in PRPF31 (pre-mRNA processing factor 31) under an autosomal dominant RP pattern, reported to account for approximately 5–10% of all dominant RP cases in the medical literature. PRPF31 is located on chromosome 19 and encodes the PRPF31 protein which is a pre-mRNA splicing factor involved in coupling of the spliceosome – a vital part of the protein synthesis and pathogenic variants in PRPF31, resulting less efficient splicing and thus an impaired protein synthesis. The disease mechanism is haploinsufficiency and PRPF31 is ubiquitously expressed in all tissues in the body, but only retina-specific disease has been described, most likely due to high splicing demands in the retina. Cases of non-penetrance with asymptomatic carriers are well described in PRPF31.
In the Danish study, the researchers included 46 subjects with RP11 with a median age of disease onset was 10 years (range 5–65). The follow-up duration, spanned from 0 to 36 years (with a median of 8 years), reported median Goldmann visual field areas decreased by 10.0% per year (95% CI 7.5%−12.4%) with target IV4e, 7.9% (95% CI 4.5% − 11.2%) with target III4e, and 9.3% (95% CI: 7.0% −11.5%) when combining target sizes. Visual acuity measurements were available for 45 individuals distributed on 189 visits (median 3 visits per individual, range 1–20). Visual acuity measurements from the better seeing eye ranged from 20/15 to hand movements (equals −0.11 to 3.0 on the logMAR scale). Only one individual had, at any follow-up, registered a best-corrected visual acuity of less than 20/200 (logMAR 1.0) on their better seeing eye. The trend was that visual acuity decreases over time. In conclusion, the researchers commented that “this study contributes to improved counselling of patients with this subtype of RP and describe the largest population to date. The progression of visual field loss in these individuals will aid to a better prediction of prognosis in a patient with RP11. Ultimately, natural history data are useful in future treatment trials, and our study suggests that kinetic visual fields could be useful in monitoring subjects with RP11 in such trials”.