Abstract：
Hearing loss constitutes one of the most prevalent conditions within the field of otolaryngology. Recent investigations have revealed that mutations in deafness-associated genes, including point mutations and variations in DNA sequences, can cause hearing impairments. With the ethology of deafness remaining unclear for a substantial portion of the affected population, further screenings for pathogenic mutations are imperative to unveil the underlying mechanisms. On this study, by using next-generation sequencing, we examine 129 commonly implicated deafness-related genes in a Chinese family with hearing loss, revealing a novel heterozygous dominant mutation in the GJB2 gene (GJB2: c.65T>G: p. Lys22Thr). This mutation consistently occurs in affected family members but is not detected in unaffected individuals, strongly suggesting its causative role in hearing loss. Structural analysis indicates potential disruption to the Cx26 gap junction channel\'s hydrogen bond and electrostatic interactions, aligning with predictions from the PolyPhen and SIFT algorithms. In conclusion, our study provides conclusive evidence that the identified heterozygous GJB2 mutation (GJB2: c.65T>G: p. Lys22Thr), specifically the K22T alteration, is the primary determinant of the family\'s deafness. This contribution enhances our understanding of the interplay between common deafness-associated genes and hearing loss, offering valuable insights for diagnostic guidance and the formulation of therapeutic strategies for this condition.
摘要：
听力损失是耳鼻喉科领域中最普遍的疾病之一。最近的研究表明，耳聋相关基因的突变，包括DNA序列的点突变和变异，会导致听力损伤。由于大部分受影响人群的耳聋行为学仍然不清楚，进一步筛查致病性突变对于揭示潜在机制至关重要.在这项研究中，通过使用下一代测序，我们检查了中国听力损失家庭中129个常见的耳聋相关基因，揭示了GJB2基因中的一个新的杂合显性突变(GJB2:c.65T>G:p.Lys22Thr)。这种突变始终发生在受影响的家庭成员中，但在未受影响的个体中未检测到。强烈暗示其在听力损失中的致病作用。结构分析表明Cx26间隙连接通道的氢键和静电相互作用的潜在破坏，与PolyPhen和SIFT算法的预测保持一致。总之,我们的研究提供了确凿的证据，即已鉴定的杂合GJB2突变（GJB2：c.65T>G：p.Lys22Thr），特别是K22T改造，是家庭耳聋的主要决定因素。这一贡献增强了我们对常见耳聋相关基因与听力损失之间相互作用的理解，为这种情况的诊断指导和治疗策略的制定提供有价值的见解。
