Vasil Kostin, Karolina Kaminska, Marco Cattaneo, Enrico Ambrosini, Carmen Ayuso, Almudena Ávila-Fernández, Béatrice Bocquet, Luisa Coutinho-Santos, Benedetto Falsini, Lidia Fernandez-Caballero Palomeque, Bohdan Kousal, Petra Liskova, Inmaculada Martín-Mérida, María Juliana Ballesta-Martínez, Daan Panneman, Susanne Roosing, Isabelle Meunier, José M Millán, Monika Pankievič, Irene Perea-Romero, Virginie Peter, Giorgio Placidi, Cristina Santos, Francesca Simonelli, Ana Berta Sousa, Francesco Testa, Marie Vajter, Marianna Weener, Mathieu Quinodoz, Carlo Rivolta, Giacomo Calzetti
Biallelic PRCD variants cause autosomal recessive retinitis pigmentosa, most often manifesting during childhood and showing relatively rapid progression of visual function loss. This information could prove useful for patient counselling and the planning of prospective natural history studies and targeted therapeutic approaches.
PURPOSE: To describe the clinical and genetic characteristics of patients with biallelic disease-causing variants in the PRCD (Progressive Rod-Cone Degeneration) gene.
METHODS: Multicentre, retrospective cohort study of 19 patients from 13 families across nine reference centres in six countries. Clinical assessments included best-corrected visual acuity (BCVA), kinetic visual field (VF), optical coherence tomography, and fundus autofluorescence (FAF). BCVA and VF area progression rates were estimated using linear mixed models on log-converted variables. Genetic testing was performed via Sanger sequencing, targeted gene panels, whole-exome sequencing, or whole-genome sequencing.
RESULTS: Median age at symptom onset was 11 years, with nyctalopia as the main initial complaint. Mean age at low vision and legal blindness in the best-seeing eye was 35 and 38 years, respectively. BCVA declined at 0.046 logMAR/year (95% CI: 0.027-0.065; p < 0.001), corresponding to a 10.0% annual loss. VF area (V4e isopter) decreased by 19.4% annually. The time to reach the limit of significant change was <2 years for both BCVA and VF area. FAF showed a gradient from hyperautofluorescent arc in the youngest patient to extensive atrophy in older patients with advanced disease. Five distinct loss-of-function variants were identified, including two nonsense, two splice-site variants, and a whole-gene deletion.
CONCLUSION: Biallelic PRCD variants cause autosomal recessive retinitis pigmentosa, most often manifesting during childhood and showing relatively rapid progression of visual function loss. This information could prove useful for patient counselling and the planning of prospective natural history studies and targeted therapeutic approaches.