| 摘要: |
| 目的 探索广西地区听力筛查未通过患儿特异性基因突变谱，评估全基因组测序（Whole Genome Sequencing，WGS）在本研究队列的分子诊断检出情况。方法 回顾性分析2022年4月-2024年10月64例广西地区听力筛查未通过且经客观听力学检查确诊为感音神经性听力损失的患儿临床资料。采用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（American College of Medical Genetics and Genomics，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失为主。WGS结果显示，26.56%患儿未检出可解释表型的致病性（Pathogenic，?P）/?可能致病性（Likely Pathogenic，?LP）变异，45.31%检出单基因变异，28.13%检出多基因变异。GJB2基因变异在本队列中检出频率较高，共发现SLC26A4 c.918+1G>A等18个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。本研究为单中心小样本回顾性研究，可为区域耳聋基因变异谱的研究提供补充，并为将来大队列研究、家系验证以及功能研究提供线索，其人群代表性和临床推广价值仍需进一步验证。 |
| 关键词: 耳聋 听力筛查 全基因组测序 突变位点 |
| DOI： |
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| 基金项目:广西壮族自治区卫生健康委员会自筹经费科研课题(Z-A20220004)；广西壮族自治区科学技术厅青年科学(2024GXNSFBA010186)；广西壮族自治区科学技术厅重点研发计划(桂科AB17292089)。 |
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| Whole Genome Sequencing Results of 64 Children with Hearing Screening Failure in Guangxi |
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tangjie
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THE PEOPLES HOSPITAL OF GUANGXI ZHUANG AUTONOMOUS REGION
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| Abstract: |
| Objective To characterize the region-specific genetic variant spectrum in children from Guangxi who failed newborn hearing screening, and assess the molecular diagnostic yield of whole genome sequencing (WGS) in this cohort. Methods Clinical data of 64 Guangxi children with hearing screening failure confirmed by objective audiometric examination as sensorineural hearing loss from April, 2022 to October, 2024 were retrospectively analyzed. Hearing levels were graded using multiple auditory steady-state response, and WGS was performed on peripheral blood samples. Genetic variants were screened and annotated through standard protocols, with pathogenicity grading according to the guidelines of the American College of Medical Genetics for Molecular Pathology (ACMG). Results Among 64 children, bilateral profound hearing loss was the predominant manifestation. WGS results showed that no phenotype-explanatory pathogenic (P) or likely pathogenic (LP) variants were identified in 26.56% of children, while 45.31% exhibited single-gene variants and 28.13% showed multi-gene variants. Variations in GJB2 were frequently identified in this cohort. 18 novel mutation sites were identified, including SLC26A4 c.918+1G>A, and all were not previously reported in any databases or literature sources. Conclusion The genetic etiology of children who failed hearing screening in Guangxi region exhibits significant heterogeneity. This single-center, small-sample retrospective study provides data for supplementing the regional deafness gene variant spectrum, and offers insights for future large-scale cohort studies, family-based validation and functional research. However, its population representativeness and clinical generalizability requires further validation. |
| Key words: deafness hearing screening whole genome sequencing mutation site |
