The genetic landscape of inherited retinal dystrophies in Arabs.

Inherited retinal dystrophies (IRDs) are a major cause of vision loss. Altogether are highly heterogeneous genotypically and phenotypically, exhibiting substantial differences worldwide. To shed more light on these conditions, we investigated the genetic and phenotypic landscape of IRDs in the Arabs globally and per country.We analyzed 1,621 affected individuals from 16 Arabic countries reported in 198 articles. At the phenotypic level, rod-cone dystrophy (RCD) and Usher syndrome were the most prevalent conditions among non-syndromic and syndromic IRDs. At the gene level, TULP1, ABCA4, RP1, CRB1, MYO7A, RPE65, KCNV2, and IMPG2 were the most mutated genes. Interestingly, all except CRB1 were highly prevalent because they harbored founder mutations, implying that consanguinity is a major determinant in Arab countries. Of note, ~ 93% of the investigated individuals carried homozygous mutations. The country analysis for the IRDs conditions and their associated genotypes revealed that whereas Leber Congenital Amaurosis, RCD, and USHER syndrome were widely distributed, bestrophinopathies and non-syndromic hearing loss were restricted to specific countries (till now).This study could be a starting point for initiating suitable health policies towards IRDs in the Arab world. The high degree of homozygosity urges the need for genetic counsellors to provide personalized information and support the affected individuals.

The research output of rod-cone dystrophy genetics.

Non-syndromic rod-cone dystrophy (RCD) is the most common condition in inherited retinal diseases. The aim of this study was to evaluate the research output and productivity related to RCD genetics per countries as classified by the human development index (HDI), by analyzing publication frequency and citations, the choice of journals and publishers, since 2000 to date. We have also analyzed the use of next-generation sequencing (NGS) in publications originating from countries with different HDIs. One thousand four hundred articles focusing on non-syndromic RCD were downloaded and analyzed. Citations and published articles were adjusted per one million individuals. The research output is significantly higher in very high HDI countries (86% of the total publications and 95% of the citations) than countries with lower HDIs in all aspects. High and medium HDI countries published together 13.6% of the total articles worldwide and received 4.6% of the citations. On the publication level, the USA (26%), United Kingdom (10%), and Japan (7%) were the top 3 among very high HDI countries, while China (6%) and India (2%) ranked first in high and medium HDI countries respectively. On the citation level, similar profiles were found. Following adjustment for population size, Switzerland (~14%), Jordan (~ 1%) and Morocco (<0.2%) showed the highest rates of publications in very high, high and medium HDI countries respectively. Very high HDI countries published 71% of their papers in first quartile journals (first quartile in Scimago journal rank; Q1), and 23% in Q2 journals. High and medium HDI countries showed a similar profile in quartiles with ~ 40% of their papers published in Q1 journals and ~ 30% in Q2 journals. The first publication using NGS was issued in 2009 in very high HDI countries, while it appeared in 2012 in high HDI countries, and in 2017 in medium HDI countries, with a respective lag of 3 to 8 years compared to very high HDI countries. A profound gap exists between very high HDI countries and the rest of the world. To fill it in, we propose implementing NGS, supporting international collaborations, building capacities and infrastructures, improving accessibility of patients to services, and increasing national and international funding.

The genetics of rod-cone dystrophy in Arab countries: a systematic review.

Since a substantial difference in the prevalence of genetic causes of rod-cone dystrophy (RCD) was found among different populations, we conducted a systematic review of the genetic findings associated with RCD in Arab countries. Of the 816 articles retrieved from PubMed, 31 studies conducted on 407 participants from 11 countries were reviewed. Next-generation sequencing (NGS) was the most commonly used technique (68%). Autosomal recessive pattern was the most common pattern of inheritance (97%) and half of the known genes associated with RCD (32/63) were identified. In the Kingdom of Saudi Arabia, in addition to RP1 (20%) and TULP1 (20%), gene defects in EYS (8%) and CRB1 (7%) were also prevalently mutated. In North Africa, the main gene defects were in MERTK (18%) and RLBP1 (18%). Considering all countries, RP1 and TULP1 remained the most prevalently mutated. Variants in TULP1, RP1, EYS, MERTK, and RLBP1 were the most prevalent, possibly because of founder effects. On the other hand, only ten Individuals were found to have dominant or X-linked RCD. This is the first time a catalog of RCD genetic variations has been established in subjects from the Arabi countries. Although the last decade has seen significant interest, expertise, and an increase in RCD scientific publication, much work needs to be conducted.