Genetic characterization of inherited retinal dystrophy in a Northwestern Chinese cohort: A single-center study over a 5-year period in Shaanxi, China

Inherited retinal diseases (IRDs) are a clinically and molecularly heterogeneous group of monogenic disorders that cause vision loss across all age groups. This study set out to define the mutational landscape of IRDs among patients evaluated at a tertiary center in Northwest China. Next-generation sequencing (NGS) was performed in 116 patients with IRDs enrolled at our ophthalmic center over a five-year recruitment period. Of these, 92 underwent whole-exome sequencing (WES) and the remaining 24 were analyzed with a targeted hereditary eye disease enrichment panel (HEDEP). Co-segregation analysis involving family members was completed for 111 probands. In total, 129 sequence alterations were detected, of which 60 were novel. The potential molecular diagnostic rate was 69%. High detection rates were observed in clinically well-defined conditions: Stargardt disease, congenital stationary night blindness, fundus albipunctatus, and Bardet-Biedl syndrome each reached 100% diagnostic confirmation. Diagnostic success was greater among patients with available family co-segregation data (70.2%), children and adolescents (76.7%), and those enrolled within the most recent two years (76.2%). Among the 80 molecularly solved/possibly solved cases, autosomal dominant transmission accounted for 17.5%, autosomal recessive inheritance predominated at 65%, and X-linked inheritance accounted for 17.5%. ABCA4 was the most frequently mutated gene in this cohort, followed by BEST1 and CRB1. Notably, no EYS variants were identified, whereas variants in the RDH gene were seen at a relatively higher frequency. The present work provides a comprehensive molecular characterization of IRD patients from Northwest China evaluated at a tertiary center in Shaanxi and describes the genetic characteristics of this regional cohort. These observations may help refine diagnostic algorithms for retinal disorders and inform the development of broadly applicable precision treatments.