Research on a nation-wide study conducted in Israel has collated the largest cohort of inherited retinal disease (IRDs) to date. The Israel inherited retinal disease consortium (IIRDC) has outlined a genetic analysis of IRD patients showing that retinitis pigmentosa (43%) was the most common phenotype, followed by Stargardt’s disease, cone/cone–rod dystrophy and Usher syndrome (8% each). The most frequently mutated genes in the study identified ABCA4, USH2A, FAM161A, CNGA3, and EYS. Inherited retinal disease is one of the most genetically heterogeneous groups of disorders including autosomal recessive (AR), autosomal dominant (AD), X‐linked (XL), mitochondrial and digenic patterns of inheritance, comprising over 260 genes implicated in the aetiology of IRD.
Israel has just under 9 million inhabitants with a highly heterogeneous population, including Jews (74% of the population), Arab Muslims (19.5%), Arab Christians (1.5%), Druze (1.6%), and several other ethnic groups. Some sub-populations in the country have high rates of consanguinity and a high number of siblings per family, leading to an increased rate of recessively‐inherited diseases. Non-syndromic retinitis pigmentosa (RP) clearly compares between Europe/USA vs. the Jerusalem region – in Europe and USA, RP has a prevalent estimate of 1/5,000, compared to an estimate of 1/2,100 in Jerusalem (both in the Jewish and Arab Muslim populations). In an analysis of the current research study, the Israel consortium reported a total of 3,413 IRD patients from 2,420 families recruited between the years 1999 and 2018. Aside from among the most common phenotype, USH had the most common type of syndromic IRD (60% of syndromic families), followed by Bardet–Biedl syndrome (1.6% of total families). Arab Muslims constituted the largest ethnic group in the current cohort (25%), followed by Ashkenazi Jews (20%). From their analysis, the overall IRD prevalence in Israel expected to be higher than 1:1,000, indicating an approximately 9,000 IRD patients in Israel, comparing a similar proportionate population reported in a recent Irish study (5,000 IRD patients). In all, the 3,413 patients described in the Israeli study constituted 38% of all Israeli IRD patients. The outcome of the study also identified 605 distinct pathogenic variants in 129 distinct genes, including various missense mutations (46%), nonsense (18%), frameshift (17%), and splice‐site (12%), large deletions (5%), and others.
The research study was important for several reasons, supporting an accurate clinical diagnosis for patients, assessing genetic screening and counselling information for high‐risk populations, establishing genotype–phenotype correlations, to identify novel disease genes and mechanisms and, more rapidly identify patients who might benefit from emerging gene‐based therapies. In concluding in their research paper (Human Mutation, 2019.), the authors commented 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. Furthermore, the study should facilitate treatment of IRD patients, via identification of patient groups with shared genetic diagnoses, who can be treated accordingly”.