Human Genetics and Stem Cell Research Group, Research Institute of Sciences and Engineering, University of Sharjah, Sharjah, United Arab Emirates.
Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah, United Arab Emirates.
Int J Pediatr Otorhinolaryngol. 2021 Jan;140:110467. doi: 10.1016/j.ijporl.2020.110467. Epub 2020 Nov 9.
The development of next generation sequencing-based techniques showed an important progress in the identification of pathogenic variants related to monogenetic diseases with genetic and phenotypic heterogeneities. Hereditary hearing loss is considered as one of these heterogeneous diseases, given the large number of deafness causing genes, the different modes of inheritance and the phenotypic variabilities associated to the severity, age of onset and/or presence or absence of other clinical manifestations.
In this study, we performed next-generation sequencing (NGS) in 51 UAE patients with hearing loss and no GJB2 mutations. In addition, we reviewed all reported SLC26A4 missense mutations with a confirmed DFNB4/Pendred syndrome phenotype and tried to find a genotype/phenotype correlation using different criteria.
By analyzing the NGS data, we identified one new SLC26A4 variant c.1150G > C (p.Glu384Gln) and one known SLC26A4 mutation c.716T > A (p.Val239Asp) in two different patients. Direct Sanger sequencing and segregation analyses confirmed the implication of both DNA variants in the deafness phenotype. Moreover, the clinical examination of both patients showed that one patient has syndromic deafness (Pendred syndrome) and the second one has non-syndromic deafness. The analysis of all confirmed missense mutations didn't reveal a complete genotype/phenotype correlation.
To the best of our knowledge, this is the first report of mutations associated with DFNB4/Pendred deafness in the GCC region.
基于下一代测序技术的发展，在鉴定具有遗传和表型异质性的单基因疾病相关致病变异方面取得了重要进展。遗传性听力损失被认为是这些异质性疾病之一，因为导致耳聋的基因数量众多，遗传方式不同，以及与严重程度、发病年龄和/或是否存在其他临床表现相关的表型变异性。
在这项研究中，我们对 51 名患有听力损失且无 GJB2 突变的阿联酋患者进行了下一代测序（NGS）。此外，我们回顾了所有报道的具有明确 DFNB4/Pendred 综合征表型的 SLC26A4 错义突变，并尝试使用不同标准寻找基因型/表型相关性。
通过分析 NGS 数据，我们在两名不同的患者中发现了一个新的 SLC26A4 变体 c.1150G>C (p.Glu384Gln) 和一个已知的 SLC26A4 突变 c.716T>A (p.Val239Asp)。直接 Sanger 测序和分离分析证实了这两种 DNA 变异均与耳聋表型有关。此外，对两名患者的临床检查表明，一名患者患有综合征性耳聋（Pendred 综合征），另一名患者患有非综合征性耳聋。对所有确认的错义突变的分析并未揭示出完全的基因型/表型相关性。
据我们所知，这是 GCC 地区首次报道与 DFNB4/Pendred 耳聋相关的突变。
