A phenotype-genotype study of X-linked retinoschisis in RS1 mutations / 中华实验眼科杂志

Objective:To describe the characteristics of genotype and phenotype in 3 families with X-linked retinoschisis (XLRS) due to RS1 mutations. Methods:A cross-sectional approach was adopted.Three XLRS families at the Ningxia Eye Hospital from October 2017 to March 2019 were included.Clinical data and peripheral blood of patients and related families were collected and clinically staged were formulated through a comprehensive eye examination.The disease-causing genes screened by panel sequencing underwent conservative analysis, pathogenicity analysis and protein structure prediction by software tools.Analysis of the mutations pathogenicity was performed according to the American College of Medical Genetics and Genomics guidelines.The research was approved by Medical Ethics Committee of the People's Hospital of Ningxia Hui Autonomous Region and followed the Declaration of Helsinki.Written informed consent was obtained from each participant.Results:Total 5 young male patients and 1 middle-aged patient in these three families.The optical coherence tomography(OCT) findings of 5 young patients showed typical macular retinoschisis, which were characterized by stage I of XLRS.One middle-aged patient (Ⅱ-9) showed a stage Ⅲ lesion of macular atrophy.The mutations of c. 668G>A, c.618G>A and exon 1 deletion in RS1 gene were found in the three families.C223 and W206 were verified to be highly conserved in mammals and were predicted to be pathogenic mutations by software and the change of protein structure.Conservation analysis and prediction of protein structure were not performed for the mutation of exon 1 deletion.All the mutations were pathogenic variants according to the ACGM guidelines. Conclusions:Mutations of c. 668G>A/p.C223Y, c.618G>A/p.W206X and exon 1 deletion in RS1 gene are pathogenic mutations in Chinese XLRS families.The combination of Panel sequencing with pathogenicity analysis and protein structure prediction have important effect to diagnosis and identify the causative genes for the hereditary retinal diseases.