Whole exome sequencing (WES) is a powerful technique for identifying sequence changes in the human genome. The goal of this study was to delineate the genetic defects in patients with inherited retinal diseases (IRDs) using WES. WES was performed on 90 patient DNA samples from 68 families and 226 known genes for IRDs were analyzed. Sanger sequencing was used to validate potential pathogenic variants that were also subjected to segregation analysis in families. Thirty-three causative mutations (19 novel and 14 known) in 25 genes were identified in 33 of the 68 families. The vast majority of mutations (30 out of 33) have not been reported in the Israeli and the Palestinian populations. Nine out of the 33 mutations were detected in additional families from the same ethnic population, suggesting a founder effect. In two families, identified phenotypes were different from the previously reported clinical findings associated with the causative gene. This is the largest genetic analysis of IRDs in the Israeli and Palestinian populations to date. We also demonstrate that WES is a powerful tool for rapid analysis of known disease genes in large patient cohorts.
Bibliographical noteFunding Information:
Some of the data were collected by two clinical researchers who passed away during the study: Prof. David Ben-Ezra and Prof. Saul Merin. This study was supported by the Foundation Fighting Blindness USA (BR-GE-0510-0490-HUJ and BR-GE-0214-0639 to DS), Binational US-Israel foundation (BSF-grant number 2011202 to DS and AS), the Yedidut 1 research grant (to EB) and the intramural research program of the National Eye Institute, National Institutes of Health, USA (to AS).