The purpose of this study was to expand the mutation spectrum by searching the causative mutations in nine Lebanese families with Usher syndrome (USH) using whole-exome sequencing. The pathogenicity of candidate mutations was first evaluated according to their frequency, conservation, and in silico prediction tools. Then, it was confirmed via Sanger sequencing, followed by segregation analysis. Finally, a meta-analysis was conducted to calculate the prevalence of USH genes in the Lebanese population. Three missense mutations, two splice site mutations, and one insertion/deletion were detected in eight of the families. Four of these variants were novel: c.5535C > A; p.(Asn1845Lys) in exon 41 of CDH23, c.7130G > A; p.(Arg2377Gln) in exon 32 of ADGRV1, c.11390-1G > A in USH2A, and c.3999–6A > G in PCDH15. All the identified mutations were shown to be likely disease-causing through our bioinformatics analysis and co-segregated with the USH phenotype. The mutations were classified according to the ACMG standards. Finally, our meta-analysis showed that the mutations in ADGRV1, USH2A, and CLRN1 are the most prevalent and responsible for approximately 75% of USH cases in Lebanon. Of note, the frequency USH type 3 showed a relatively high incidence (23%) compared to the worldwide prevalence, which is around 2–4%. In conclusion, our study has broadened the mutational spectrum of USH and showed a high heterogeneity of this disease in the Lebanese population.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.