Genetic etiology of hereditary hearing loss in the Gulf Cooperation Council countries

Abstract

The past 30 years have seen an exponential growth concerning the identification of genes and variants responsible for hereditary hearing loss (HL) worldwide. This has led to a huge gain in our understanding of molecular mechanisms of hearing and deafness, which improved diagnosis for populations with hereditary HL. Many communities around the world, especially in the Middle East and North Africa, have a high prevalence of consanguineous marriages. Congenital monogenic conditions, such as recessive HL, are more common in these populations due to high consanguinity rates. Many studies have shown that high rates of consanguinity, endogamy, and first cousin marriages were observed in the six countries of the Gulf Cooperation Council (GCC). The intent of this study is to investigate the etiology of HL in the GCC region. A deep literature review of genes and variants responsible for HL in this region revealed 89 recessive DNA pathogenic variants reported in 138 cases/familial cases. A total of 21 genes responsible for non-syndromic hearing loss (NSHL) and 17 genes associated with syndromic hearing loss (SHL) were reported in cases from the GCC region. Out of 156 reported affected cases, 112 showed HL only, and 44 showed HL associated with other clinical manifestations. This data suggests that in the GCC region 72% of HL forms are non-syndromic and 28% are syndromic. For individuals with NSHL, 66% of variants were detected in four genes (GJB2, OTOF, TMC1 and CDH23), with a predominance of variants located in the GJB2 gene (37.5%). However, among SHL, Usher syndrome was the more frequent as it has been observed in 41% of the reported syndromic GCC cases. Finally, our analysis showed that HL genetics testing and research in the GCC region took advantage of the next generation sequencing (NGS)-based techniques, as approximately 58% of reported variants were identified using this technology.