Comprehensive analysis of RS1 gene mutations and clinical manifestations in nine unrelated X-linked retinoschisis (XLRS) Chinese families

Purpose X-linked retinoschisis (XLRS) is an X-linked recessive (XLR) inherited retinal disease. Accurate diagnosis of XLRS is difficult because of its diverse clinical presentations and genetic heterogeneity. However, molecular methods can aid in making an accurate diagnosis, especially for patients with no typical pathologic symptoms. The aim of this study was to identify genetic defects in patients from nine nonconsanguineous XLRS families via genetic screening and investigate the associations between genotypes and clinical phenotypes. Methods Nine unrelated Chinese XLRS patients and their family members were recruited for genetic screening. Ophthalmologic data was obtained from all patients. Gene mutations were identified using targeted exome sequencing (TES) and genetic analysis. The results were validated in available family members by Sanger sequencing and co-segregation analysis. Results We successfully identified seven RS1 gene mutations in nine nonconsanguineous Chinese patients with binocular retinoschisis. Of these, one mutation (c.420_423delinsA) was a novel mutation, and the patient presented with binocular macular and peripheral retinoschisis. All patients were male, and female carriers had no clinical symptoms, which is consistent with an XLR inheritance pattern. RS1 mutations were concentrated in exons 4, 5 and 6, most mutations were missense mutations, all of which caused changes in the discoidin domains of retinoschisin 1 (RS1). Conclusion This study reveals the importance of genetic screening in the clinical diagnosis of XLRS patients with different phenotypes and reports a novel RS1 gene mutation. Comprehensive analysis of the correlations between RS1 genotypes and clinical phenotypes can improve the accurate diagnosis and treatment of XLRS.