Clinico Hearingaid Asia Co., Ltd.; Institute of Biomedical Sciences, Mackay Medical College, No. 46, Sec. 3, Zhongzheng Rd., Sanzhi Dist., 252 New Taipei City, Taiwan; Department of Audiology and Speech-Language Pathology, Mackay Medical College, New Taipei City, Taiwan.
Department of Audiology and Speech-Language Pathology, Mackay Medical College, New Taipei City, Taiwan; Department of Otolaryngology, Mackay Memorial Hospital, Taipei, Taiwan.
Hear Res. 2022 Jan;413:108135. doi: 10.1016/j.heares.2020.108135. Epub 2020 Nov 30.
Hearing loss, the most common sensory abnormality, is caused by the death of or damage to inner ear hair cells. Genetic mutations are the main cause of hearing loss. We used nex-generation sequencing data released by the Taiwan Biobank to investigate the GJB2 mutation spectrum in 1517 patients. We compared hearing function in Taiwanese patients with nonsyndromic hearing loss (NSHL) caused by the two most common GJB2 mutations c.109G>A (p.V37I) and c.235delC. We extracted DNA from the oral mucosa of patients with NSHL and performed Sanger sequencing to confirm the genotype. Of 240 patients with NSHL, we identified 25 with GJB2 c.109G>A and 9 with GJB2 c.235delC mutations, after excluding patients aged >10 years, in whom hearing loss may have been caused due to age-related degeneration. We investigated genotype-phenotype correlations in patients harboring GJB2 c.109G>A and c.235delC mutations. Furthermore, we described the GJB2 mutation spectrum in the Taiwanese population and identified the role of homozygous and heterozygous GJB2 mutations associated with hearing phenotypes in patients with NSHL. Thus, our study provides insights into the complexity of GJB2 genetics. Our data indicate that GJB2 c.109G>A heterozygotes had poorer hearing than did homozygotes. The mechanism underlying the more severe phenotype in heterozygotes and whether the phenotype is caused by GJB2 heterozygotes or compound heterozygotes warrant future investigation.
听力损失是最常见的感觉异常，由内耳毛细胞的死亡或损伤引起。基因突变是听力损失的主要原因。我们使用台湾生物银行发布的下一代测序数据，调查了 1517 名非综合征性听力损失（NSHL）患者中 GJB2 突变谱。我们比较了台湾 GJB2 两个最常见突变 c.109G>A（p.V37I）和 c.235delC 引起的 NSHL 患者的听力功能。我们从 NSHL 患者的口腔粘膜中提取 DNA，并进行 Sanger 测序以确认基因型。在 240 名 NSHL 患者中，排除了年龄> 10 岁的患者，因为年龄相关性退变可能导致这些患者的听力损失，在这些患者中，我们确定了 25 名 GJB2 c.109G>A 突变和 9 名 GJB2 c.235delC 突变患者。我们研究了携带 GJB2 c.109G>A 和 c.235delC 突变的患者的基因型-表型相关性。此外，我们描述了台湾人群中的 GJB2 突变谱，并确定了 GJB2 突变与 NSHL 患者听力表型相关的纯合和杂合突变的作用。因此，我们的研究提供了对 GJB2 遗传学复杂性的深入了解。我们的数据表明，GJB2 c.109G>A 杂合子的听力比纯合子差。杂合子中更严重表型的机制以及表型是否由 GJB2 杂合子或复合杂合子引起，值得未来进一步研究。
