Unraveling RP1-Associated Retinal Dystrophies: Comprehensive Genetic, Clinical, and Disease Progression Analysis in China

Abstract

Purpose To characterize the clinical manifestations, genetic landscape, and natural history of RP1-associated retinopathy in a Chinese cohort. Methods This longitudinal cohort study enrolled and followed 49 patients with genetically confirmed RP1-associated retinopathy. Phenotyping included visual acuity (VA), visual field, full-field stimulus testing (FST), microperimetry, and multimodal imaging. Genetic analysis and variant interpretation followed American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines. Results The cohort predominantly presented with retinitis pigmentosa (RP, 91.8%) and bilateral involvement, with overall no significant interocular differences in major functional parameters (all P > 0.05). Median symptom onset age was 20 years (interquartile range, 7.25–33.75). On linear regression analysis, earlier onset age (P = 0.024) and longer disease duration (P = 0.019) correlated with worse VA. Kaplan–Meier analysis estimated that the median age at which patients reached blindness (>1.3 logarithm of the minimum angle of resolution [logMAR]) was 74 years. Quantified decline rates included VA (0.015 logMAR/year) and visual field index (−7.8%/year) in the first decade and FST (0.167 log cd·s/m2/year) and retinal sensitivity (−1.22 dB/year) over two decades. Classic bone-spicule pigmentation was absent in 33.3% of patients. Genetic analysis identified 46 variants; truncating mutations (71.7%) clustered in exon 4, with c.5797C>T as a founder variant (16.3% of alleles). Variants within the upstream one-third of exon 4 were associated with later onset (P = 0.049). Conclusions RP1-associated retinopathy manifests as bilateral, atypical RP with quantifiable, duration-dependent decline and a genotype–phenotype correlation linking upstream exon 4 variants to later onset. Translational Relevance Quantified progression rates and genotype–phenotype correlations inform clinical trial endpoints and patient counseling.