Cologne Center for Genomics, University of Cologne, Cologne, Germany.
Audiology Unit, Department of Otolaryngology, Faculty of Medicine, Assiut University, Egypt.
Clin Genet. 2020 Jul;98(1):32-42. doi: 10.1111/cge.13754. Epub 2020 Apr 23.
Nonsyndromic hearing loss is an extremely heterogeneous disorder. Thus, clinical diagnostics is challenging, in particular due to differences in the etiology of hearing loss between populations. With this study, we wanted to elucidate the genetic basis of hearing loss in 61 consanguineous Egyptian families. In 25 families, linkage analysis was used as a prescreening to identify regions for targeted sequencing of candidate genes. Initially, the coding regions of 12 and later of 94 genes associated with hearing loss were enriched and subjected to massively parallel sequencing (MPS) with diagnostic yields of 36% and 75%, respectively. Causative variants were identified in 48 families (79%). They were found in 23 different genes with the majority being located in MYO15A (15.3%), SLC26A4 (9.7%), GJB2 (8.3%), and MYO7A (6.4%). As many as 32 variants were novel ones at the time of detection. Five variants were shared by two, three, or even four families. Our study provides a first survey of the mutational spectrum of deaf patients in Egypt revealing less GJB2 variants than in many European populations. It underlines the value of targeted enrichment of well-selected deafness genes in combination with MPS in the diagnostics of this frequent and genetically heterogeneous disorder.
非综合征性听力损失是一种极其异质性的疾病。因此，临床诊断具有挑战性，特别是由于不同人群听力损失的病因不同。在这项研究中，我们希望阐明 61 个埃及近亲家庭听力损失的遗传基础。在 25 个家庭中，我们使用连锁分析作为预筛选，以确定候选基因靶向测序的区域。最初，富集了与听力损失相关的 12 个和后来的 94 个基因的编码区，并进行了大规模平行测序（MPS），其诊断率分别为 36%和 75%。在 48 个家庭（79%）中鉴定出了致病变异。它们存在于 23 个不同的基因中，其中大多数位于 MYO15A（15.3%）、SLC26A4（9.7%）、GJB2（8.3%）和 MYO7A（6.4%）。多达 32 个变异是在检测时发现的新变异。有 5 个变异在两个、三个甚至四个家庭中共享。我们的研究首次对埃及聋病患者的突变谱进行了调查，发现 GJB2 变异比许多欧洲人群要少。它强调了在这种常见且遗传异质性疾病的诊断中，有针对性地富集精心挑选的耳聋基因与 MPS 相结合的价值。
