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

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, targeted exome sequencing (TES) can aid in making an accurate diagnosis, especially for patients with no typical pathologic symptoms. The aim of this study was to identify pathogenic mutations in patients from nine nonconsanguineous XLRS families via genetic screening and investigate the associations between gene mutations and clinical manifestations. Nine unrelated Chinese XLRS patients and their family members were recruited for genetic screening. Demographic characteristics and ocular data, including visual acuity, intraocular pressure, and ocular manifestations, were collected from all patients. Gene mutations were identified using TES and genetic analysis. The results were validated in available family members by Sanger sequencing and co-segregation analysis. 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). 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 of XLRS.