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

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.