| 摘要: |
| ［摘要］ 目的 基于全基因组测序（WGS）探索广西地区听力筛查未通过患儿的基因突变谱。方法 招募2022年4月至2024年10月广西壮族自治区人民医院收治的、未通过听力筛查的患儿64例。通过多频稳态听觉诱发反应进行听力分级，对患儿外周血样本进行WGS检测，基因变异经标准流程筛选与注释，并依据美国分子遗传学和基因组学学院（ACMG）指南进行致病性分级。结果 64例患儿以双耳极重度听力损伤为主（54.69%，35/64）。WGS结果显示，17例（26.56%，17/64）患儿未检出可解释表型的致病（P）/可能致病（LP）变异，29例（45.31%，29/64）检出单基因变异，18例（28.13%，18/64）检出多基因变异。GJB2基因变异检出率较高（34.38%，22/64）。共发现SLC26A4 c.918+1G>A等18个在数据库及文献未报道的候选变异位点。结论 广西地区听力筛查未通过患儿的遗传学病因具有明显异质性，可为该区域耳聋基因变异谱提供补充。 |
| 关键词: 耳聋 听力筛查 全基因组测序 基因突变 变异位点 儿童 |
| DOI：10.3969/j.issn.1674-3806.2026.09.12 |
| 分类号:R 764.43 |
| 基金项目:广西科学技术厅青年科学基金项目（编号：2024GXNSFBA010186）；广西卫生健康委员会科研课题（编号：Z-A20220004）；广西科学技术厅重点研发计划项目（编号：桂科AB17292089） |
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| Whole-genome sequencing analysis of 64 pediatric patients with hearing screening failure from Guangxi region |
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Tang Jie, Chen Ruichun, Lu Lianli, Fan Mingyin, Ma Meiyan, Tang Fengzhu
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Department of Otolaryngology-Head and Neck, the People′s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China
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| Abstract: |
| ［Abstract］ Objective To investigate the gene mutation spectrum of pediatric patients from Guangxi region who failed hearing screening using whole-genome sequencing(WGS). Methods A total of 64 pediatric patients who were admitted to the People′s Hospital of Guangxi Zhuang Autonomous Region and failed hearing screening from April 2022 to October 2024 were enrolled in this study. Hearing levels were graded using multiple auditory steady-state response(ASSR). WGS was performed on peripheral blood samples collected from the enrolled pediatric patients. Genetic variants were screened and annotated through standard protocols, and their pathogenicity was classified according to the guidelines of the American College of Medical Genetics and Genomics(ACMG). Results Among the 64 pediatric patients, bilateral profound hearing loss was predominant(54.69%, 35/64). WGS results showed that no pathogenic(P) or likely pathogenic(LP) variants that could explain the phenotypes were identified in 17 pediatric patients(26.56%, 17/64); 29 pediatric patients(45.31%, 29/64) harbored single-gene variants, and 18 pediatric patients(28.13%, 18/64) carried multigenic variants. The detection rate of variants in the GJB2 gene was relatively high(34.38%, 22/64). A total of 18 candidate variant sites that had not been previously reported in databases or the literature were identified, including SLC26A4 c.918+1G>A. Conclusion The genetic etiology of pediatric patients from Guangxi region who fail hearing screening exhibits significant heterogeneity, providing a supplement to the deafness gene variant spectrum in the region. |
| Key words: deafness hearing screening whole-genome sequencing(WGS) gene mutation variant sites children |
