揭示一个中国听力损失家族中的新型 GJB2 显性 K22T 突变。

IF 3.3 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Acta biochimica et biophysica Sinica Pub Date : 2024-06-25 DOI:10.3724/abbs.2024064
Haiting Ji, Yilai Shu, Huawei Li
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引用次数: 0

摘要

听力损失是耳鼻喉科领域最常见的疾病之一。最近的研究发现,耳聋相关基因的突变(包括点突变和 DNA 序列变异)可导致听力障碍。由于大部分受影响人群的耳聋伦理仍不清楚,因此进一步筛查致病基因突变以揭示其潜在机制势在必行。本研究利用新一代测序技术,在一个中国听力损失家族中检测了 129 个常见的耳聋相关基因,发现了 GJB2 基因中的一个新型杂合子显性突变(GJB2:c.65T>G:p. Lys22Thr)。这种突变一直出现在受影响的家庭成员中,但在未受影响的个体中却检测不到,这有力地说明了它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可能受到破坏,这与 PolyPhen 和 SIFT 算法的预测一致。总之,我们的研究提供了确凿的证据,证明已确定的杂合 GJB2 突变(GJB2:c.65T>G:p. Lys22Thr),特别是 K22T 改变,是该家族耳聋的主要决定因素。这项研究加深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,为该疾病的诊断指导和治疗策略的制定提供了有价值的见解。
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Unveiling a novel GJB2 dominant K22T mutation in a Chinese family with hearing loss.

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.

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来源期刊
Acta biochimica et biophysica Sinica
Acta biochimica et biophysica Sinica 生物-生化与分子生物学
CiteScore
5.00
自引率
5.40%
发文量
170
审稿时长
3 months
期刊介绍: Acta Biochimica et Biophysica Sinica (ABBS) is an internationally peer-reviewed journal sponsored by the Shanghai Institute of Biochemistry and Cell Biology (CAS). ABBS aims to publish original research articles and review articles in diverse fields of biochemical research including Protein Science, Nucleic Acids, Molecular Biology, Cell Biology, Biophysics, Immunology, and Signal Transduction, etc.
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