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

Abstract

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.

Fig. 1. Flow chart for identifying eligible articles.

The initial search retrieved 816 papers that were filtered to leave 37 human genetics papers. When screened according to content, seven more were excluded, leaving 30 articles published from 2001 till the first of February 2020.

Fig. 2. Articles and variant identification techniques.

A Number of articles investigating the genetics of rod-cone dystrophy in Arab speaking countries until the first of February 2020. B Variant identification techniques used to report disease-causing variants.

Fig. 3. Variants spectrum in analyzed individuals from Kingdom of Saudi Arabia and North Africa.

A In individuals from Kingdom of Saudi Arabia (KSA), variants in RP1 (~20%), TULP1 (~20%), EYS (~8%), CRB1 (~7%), MERTK (~7%), and RLBP1 (~5%) account for two-thirds of the known variants. B In North Africa, the main identified genes defects were harbored in: MERTK (18%), RLBP1 (18%), RPE65 (8%), and PDE6B (8%), accounting for half of the solved cases.

Fig. 4. A histogram showing gene prevalence in Arab individuals with sporadic and autosomal recessive rod-cone dystrophy, along with a pie-chart showing their repartition in the Arab countries.

Pie-chart shows the repartition of different individuals making part of the prevalence study in the Arab countries.

Fig. 5. Map of the Arab countries showing the variations with possible founder effects and associated with sporadic and autosomal recessive rod-cone dystrophy.

Almost all variations with possible founder effects were specific to one country except; (2) c.901C>T; p.(Gln301*) in TULP1 shared in the Kingdom of Saudi Arabia and the Arabian Peninsula, (2) c.2214del; p.(Cys738Trpfs*32) in MERTK shared in the Kingdom of Saudi Arabia and the United Arab Emirates.