Al Mutery Abdullah, Mahfood Mona, Chouchen Jihen, Tlili Abdelaziz
Department of Applied Biology, College of Sciences, University of Sharjah, Building W8-Room 107, 27272, Sharjah, United Arab Emirates.
Molecular Genetics and Stem Cell Research Laboratory, University of Sharjah, Sharjah, United Arab Emirates.
Hum Genet. 2022 Apr;141(3-4):595-605. doi: 10.1007/s00439-021-02323-x. Epub 2021 Aug 2.
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.
在过去30年里，全球范围内，与遗传性听力损失（HL）相关的基因和变异的鉴定呈指数级增长。这极大地增进了我们对听力和耳聋分子机制的理解，改善了对遗传性HL人群的诊断。世界上许多社区，尤其是中东和北非地区，近亲结婚的比例很高。由于近亲结婚率高，先天性单基因疾病，如隐性HL，在这些人群中更为常见。许多研究表明，海湾合作委员会（GCC）六国的近亲结婚、族内通婚和表亲结婚率很高。本研究旨在调查GCC地区HL的病因。对该地区HL相关基因和变异进行的深入文献综述显示，在138例/家族病例中报告了89个隐性DNA致病变异。GCC地区的病例报告了总共21个与非综合征性听力损失（NSHL）相关的基因和17个与综合征性听力损失（SHL）相关的基因。在156例报告的受影响病例中，112例仅表现为HL，44例表现为HL合并其他临床表现。这些数据表明，在GCC地区，72%的HL类型为非综合征性，28%为综合征性。对于NSHL患者，66%的变异在四个基因（GJB2、OTOF、TMC1和CDH23）中被检测到，其中GJB2基因中的变异占主导（37.5%）。然而，在SHL中，Usher综合征更为常见，在报告的GCC综合征病例中占41%。最后，我们的分析表明，GCC地区的HL基因检测和研究利用了基于下一代测序（NGS）的技术，因为大约58%的报告变异是使用该技术鉴定的。
