The Israeli Inherited Retinal Diseases Consortium (IIRDC): Mapping Inherited Retinal Diseases in the Israeli Population

Abstract

Purpose : Inherited Retinal Diseases (IRDs) are the most genetically heterogeneous conditions in humans, with over 250 causative genes identified to date, and more causative genes that are yet unknown. The unique structure of the Israeli population makes it an excellent resource for finding new causative genes for IRD and for studies of new therapies designed for specific IRD populations. The purpose of the study is to recruit, clinically characterize, and genetically diagnose the majority of Israeli patients with IRD.

Methods : A consortium, IIRDC (the Israeli IRD Consortium) was established that covers the whole of Israel and includes 6 genetic centers, 5 units for clinical electrophysiology of vision, and a bioinformatics lab. The clinical centers diagnose and characterize the phenotype of the IRD patients, who are then referred to the genetic centers, whose role is to seek the causative genes and mutations. The bioinformatic center analyzes data from next generation sequencing performed by the genetic centers. Ophthalmologic analysis includes visual acuity testing, visual field, electroretinography, and imaging.

Results : Our cohort of recruited IRD families currently contains over 2000 families with various phenotypes, the most prevalent being retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), cone-rod degeneration (CRD), and Usher syndrome. We performed different genetic analyses on this set of patients including genotyping of founder mutations, homozygosity mapping, and whole exome sequencing and were able to identify the cause of disease in about 45% of families. The most common causative genes are FAM161A, ABCA4, USH2A, and EYS. Since the establishment of IIRDC, we were able to accelerate the rate of recruitment. In addition, IIRDC members identified a number of novel IRD-causing genes (CEP78, CEP250 and HGSNAT) and founder mutations in known genes.

Conclusions : This is a unique consortium given the nation-wide coverage. The immediate expected outcomes include an epidemiological overview of IRD distribution and etiology in the Israeli population, identification of novel causative genes and mechanisms, and genotype-phenotype correlations. The main expected long-term outcome is a significant reduction in the prevalence and “disease load” of IRD in Israel, achieved by a combination of prevention and treatment.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.