Researchers at the Hebrew University of Jerusalem and Technion‐Israel Institute of Technology, Haifa, have completed a clinical and genetic mapping of the majority of Israeli patients with inherited retinal diseases (IRDs). The study recruited 2,420 families including 3,413 individuals with IRDs. The most common inheritance pattern in the study had an autosomal recessive disease, with 60% of families. In addition, the highlights of the study indicated that the most common retinal phenotype was retinitis pigmentosa (43%), followed by Stargardt disease and cone/cone-rod dystrophy. The most frequently mutated genes recorded were ABCA4, USH2A, FAM161A, CNGA3, and EYS.
According to the report, the most common genetic lesion within IRD had missense mutations (46%), nonsense (18%), frameshift (17%), splice‐site mutations (12%), large deletions (5%), and others. The collected data showed that the most prevalent IRD phenotype was non-syndromic RP, while the most prevalent type of syndromic IRD was Usher’s (USH). The most prevalent mode of inheritance was autosomal recessive and the two most frequently mutated genes were ABCA4 (14%) and USH2A (7%). In the nationwide study, it showed that the genetic basis for the disease was in 56% of families (1,369/2,420). As identified, the distribution mode of inheritance was autosomal recessive (60%) across the cohort, followed by isolated cases (26%), autosomal dominant (8%) and X-linked (6%). The study referenced over 260 genes to have been implicated in the aetiology of IRD (RetNet, Retinal Information Network, https://sph.uth.edu/Retnet/).
The researchers outlined that the purpose of the study was multifactorial, specifically building a knowledge resource combining genotype with phenotype, ultimately using genetic screening and counselling across a nationwide resource. The information will also enable the identification of novel disease genes and mechanisms which may then provide the foundations required to build gene‐based therapeutic modalities to treat IRD patients. In commenting on their study, the researchers stated that, “the main expected long‐term outcome of this collaborative project is a significant reduction of IRD load in Israel. We hope to achieve this goal by prevention of the disease, using genetic screening and counselling in high‐risk populations.”