Whole genome sequencing in unsolved cases in Russian patients with recessive inherited retinal diseases

Abstract

Autosomal recessive forms (AR-IRD) account for the largest proportion of cases of inherited retinal diseases (more than 50% of all detected pathology). However, due to the high prevalence of pathogenic recessive variants in the general population, it is difficult to establish whether the variant is the cause of the disease or reflects an incidental carriage. Therefore, the aim of the present study was to evaluate the prospects of finding a second variant in frequent AR-IRD genes (ABCA4, CNGB3, USH2A, CRB1, RPE65, CEP290 and EYS) based on population data and to identify «elusive» variants on the second allele by routine methods using whole genome sequencing (WGS). WGS data were retrospectively analyzed for 106 patients. Of these, 45 (42.5%) were able to establish a molecular diagnosis, of whom 27 (60%) carried a variant in the target gene on the second allele. In the remaining 18 patients mutations in other genes with different types of inheritance were detected. The most common genes in which CNVs and intronic variants were more frequently reported were the EYS, USH2A, and ABCA4. WGS increased the percentage of solved cases of IRD by 3%, but this figure would be significantly higher if all patients with an unconfirmed molecular diagnosis were included in the study.