Clinical and molecular features of PRCD-associated retinopathy.

Biallelic loss-of-function variants in PRCD — nonsense, splice-site or whole-gene deletion — cause progressive rod then cone degeneration, most often starting in childhood.

This multicentre retrospective cohort study gathered 19 patients from 13 families across nine reference centres in six countries, all carrying biallelic disease-causing PRCD variants. Median age at symptom onset was 11 years, with nyctalopia as the main initial complaint, and mean age at low vision and legal blindness in the best-seeing eye was 35 and 38 years respectively. Best-corrected visual acuity declined by 0.046 logMAR/year (95% CI 0.027-0.065; p < 0.001), a 10.0% annual loss, and visual field area (V4e isopter) decreased by 19.4% annually, with time to the limit of significant change under 2 years for both measures. Fundus autofluorescence showed a gradient from a hyperautofluorescent arc in the youngest patient to extensive atrophy in advanced disease. Five loss-of-function variants were identified: two nonsense, two splice-site variants and a whole-gene deletion.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The concrete contribution is quantified and directly usable in ophthalmic genetics clinics: onset around 11 years, low vision around 35 and legal blindness around 38, with a decline steep enough to be measurable in under two years. That last point matters beyond prognosis, because a sensitive endpoint over a short horizon makes a PRCD cohort eligible for a gene therapy trial, provided these slopes are confirmed prospectively. The reservation concerns design: 19 patients followed retrospectively across nine centres, hence heterogeneous assessment protocols and a risk of selection bias towards the most symptomatic cases.

Analysis by Dr Thibaut Benquey