The Genetics of Inherited Retinal Diseases in the Israeli and Palestinian Populations: A Lesson from Populations with High Rates of Consanguinity

Abstract

Inherited retinal diseases (IRDs) are disorders that cause visual loss mainly due to photoreceptor degeneration. The prevalence of IRDs in the Israeli and Palestinian populations was reported to be higher compared to other studied populations. The structures of the Israeli and Palestinian populations are unique mainly because of the large number of ethnic groups. In addition, high rates of consanguinity and intra-community marriages resulted in a high proportion of families with autosomal recessive inheritance patterns. The study of Israeli and Palestinian IRD families resulted so far in the identification of mutations in 74 IRD genes, including 23 novel genes that were identified mainly using the homozygosity mapping and whole exome sequencing techniques. The history and tradition of these populations led to common founder mutations that are usually subpopulation-specific. Such mutations allow a more efficient genetic analysis in searching for the causative gene. However, some founder mutations are shared among different ethnicities and are likely to be the result of a common origin of these ethnic groups, which may have an estimated divergence time of a few thousand years. There is a large variability of retinal phenotypes among patients, while mutations in the same gene can result either in the same phenotype or variable phenotypes that are usually mutation-dependent. There is currently no cure for the vast majority of IRD types; however recent advances bring new hope for curing or at least delaying the degeneration process in the near future.