Do variants in the CDH23 gene cause non-syndromic retinitis pigmentosa? Dual validation using whole exome sequencing and a zebrafish model.

objectiveUsing whole exome sequencing to detect pathogenic genes in families with inherited retinal dystrophy, and also to investigate the effects of

methodsIn this study, we collected data from a patient diagnosed with retinitis pigmentosa (RP) at Ningxia Eye Hospital in 2022. Comprehensive ophthalmic and systemic examinations were conducted, and peripheral venous blood samples were obtained from the proband and family members. Whole exome sequencing was used to screen for pathogenic gene mutations in the proband, and Sanger validation was performed on the detected likely pathogenic sites. The zebrafish

resultsThe proband presented with a 20-year history of gradually progressive visual loss with nyctalopia in both eyes, with the best-corrected visual acuity of hand movements in the right eye (OD) and 0.1 in the left eye (OS). Funduscopic examination revealed pale optic discs, atrophic macular regions and large osteoclast-like pigment deposits on the retinal surface, and the retinal vasculature appeared thinner. Electroretinography suggested significant cone-rod dysfunction in both eyes and the pure tone audiometry suggested perfectly normal hearing. Whole exome sequencing revealed that the proband carried compound heterozygous variants in the CDH23 gene: c.2572G>A (p.Val858Ile) and c.8344G>A (p.Asp2782Asn), and Sanger sequencing confirmed that the phenotypically normal parents of the proband carried a heterozygous variant, respectively. Zebrafish knockdown experiments suggested that the gene variant could result in a significant thinning of the retinal photoreceptor layer, a substantial shortening of photoreceptor cell length and a sparse distribution of these cells.

conclusionIn this study, we reported the first case of non-syndromic RP resulting from a