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中国循证儿科杂志

中国循证儿科杂志 ›› 2023, Vol. 18 ›› Issue (1): 66-70.DOI: 10.3969/j.issn.1673-5501.2023.01.011

• 论著 • 上一篇    下一篇

新生儿重症监护病房新生儿耳聋基因致病变异携带者筛查的横断面调查

朱韵倩1, 5，卢宇蓝2, 5，胡黎园1，杨琳3，王来栓1，曹云1，董欣然2，许政敏4，王慧君2，吴冰冰2，周文浩1, 2   

  1. 复旦大学附属儿科医院上海, 201102， 1 新生儿科， 2 分子诊断中心， 3 临床遗传中心，4 耳鼻喉科，5 共同第一作者


  • 收稿日期:2022-03-31 修回日期:2022-05-16 出版日期:2023-02-25 发布日期:2023-02-25
  • 通讯作者: 吴冰冰，王慧君

Carrier screening for pathogenic genes for hearing loss among newborns in a neonatal intensive care unit: A cross-sectional survey

ZHU Yunqian1,5, LU Yulan2,5, HU Liyuan1, YANG Lin3, WANG Laishuan1, CAO Yun1, DONG Xinran2, XU Zhengmin4, WANG Huijun2,6, WU Bingbing2, ZHOU Wenhao1,2    

  1. Children's Hospital of Fudan University, Shanghai 201102, China; 1 Division of Neonatology；2 Center for Molecular Medicine, Pediatric Research Institute; 3 Clinical Genetic Center; 4 Department of OtolaryngologyHead and Neck Surgery;5 Co-first author
  • Received:2022-03-31 Revised:2022-05-16 Online:2023-02-25 Published:2023-02-25
  • Contact: WU Bingbing, email: 081107271@fudan. edu. cn; WANG Huijun, email: huijunwang@fudan. edu. cn

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摘要： 背景：我国耳聋发病率高与耳聋基因致病变异的携带率高有关，目前缺乏对NICU新生儿耳聋基因致病变异携带者的筛查数据。 目的：调查NICU新生儿中耳聋基因GJB2 和SLC26A4致病变异的携带率。 设计：横断面研究。 方法：纳入2016年1月至2021年12月在复旦大学附属儿科医院NICU住院、入院日龄≤28 d，且出院前完成高通量测序的新生儿，排除生后耳聋相关基因诊断阳性者。从病历系统中截取患儿的性别、胎龄、出生体重；从测序数据库中提取GJB2 基因和SLC26A4基因的检测结果、患儿人类表型标准用语信息。携带率（%）=杂合致病或可能致病（P/LP）变异例数/总研究对象人数。检索PubMed、Embase和万方数据库，纳入既往报道中国NICU人群、新生儿人群和孕妇人群中GJB2 基因和/或SLC26A4基因P/LP变异携带情况的文献，并行复习。 主要结局指标：GJB2 基因和SLC26A4基因的P/LP变异携带率。 结果：纳入14 924例新生儿，男8 587例（57.5%），女6 337例，胎龄（35.6±3.7）周，出生体重（2 711.7±887.1）g。携带GJB2 基因P/LP变异的患儿2 009例（13.462%），共检出18种杂合P/LP变异，其中c.109G>A最常见（10.902%），其次为c.235del（1.749%）、c.299_300del（0.409%）、c.176_191del（0.154%）、c.508_511dup（0.074%）和c.257C>G（0.034%）。携带SLC26A4基因P/LP变异的患儿305例（2.044%），共检出31种杂合P/LP变异，携带率最高的6种依次为c.919-2A>G（1.139%）、c.2168A>G（0.181%）、c.1226G>A（0.100%）、c.1229C>T（0.094%）、c.1174A>T（0.080%）和c.1003T>C（0.047%）。 结论：建议将GJB2 基因上的c.109G>A、c.508_511dup和c.257C>G以及SLC26A4基因的c.1003T>C位点纳入NICU新生儿耳聋基因致病变异携带者筛查。

关键词: 耳聋, 婴儿, 新生, 基因, GJB2, SLC26A4

Abstract: Background: The high prevalence of hearing loss in China is associated with a high carrier rate of pathogenic variants in genes for hearing loss. At present, there is a lack of screening data on carriers of pathogenic genes for hearing loss among newborns in neonatal intensive care units (NICU). Objective: To investigate the carrier rate of GJB2 and SLC26A4, pathogenic genes for hearing loss, in NICU newborns. Design: Cross-sectional survey. Methods: Newborns were enrolled in the NICU at Children's Hospital of Fudan University from January 2016 to December 2021, with admission days≤28 d and high-throughput sequencing completed before discharge. Those with positive hearing-loss-associated genetic findings after birth were excluded. The sex, gestational age and birth weight were collected from electronic medical records. The number of cases identified with pathogenic variants in GJB2 and SLC26A4 and the standard terminology of the human phenotype of the children were extracted from the sequencing database. Carrier rate(%)=the number of heterozygous pathogenic or likely pathogenic (P/LP) variants/total number of study subjects. PubMed, Embase, and Wanfang databases were searched. Literature that previously reported the carrier status of the GJB2 gene and/or SLC26A4 gene P/LP mutations in NICU patients, newborns and pregnant women in China were included and reviewed. Main outcome measures: Carrier rate of P/LP variants in the GJB2 gene and SLC26A4 gene. Results: A total of 14 924 neonates were included, including 8 587 males (57.5%) and 6 337 females, with a gestational age of (35.6±3.7) weeks and a birth weight of (2 711.7±887.1) g. A total of 18 heterozygous P/LP mutations were detected in 2 009 children (13.462%) carrying P/LP mutations of the GJB2 gene, among which c.109G>A was the most common (10.902%), followed by c.235del (1.749 %), c.299_300del (0.409%), c.176_191del (0.154%), c.508_511dup (0.074%) and c.257C>G. There were 305 children (2.044%) carrying P/LP mutations of the SLC26A4 gene. A total of 31 heterozygous P/LP mutations were detected, and the six highest carrier rates were for c.919-2A>G (1.139%), c. .2168A>G (0.181%), c.1226G>A (0.100%), c.1229C>T (0.094%), c.1174A>T (0.080%) and c.1003T>C, respectively. Conclusions: It is suggested that c.109G>A, c.508_511dup and c.257C>G on the GJB2 gene and c.1003T>C on the SLC26A4 gene should be included in the carrier screening for pathogenic genes for hearing loss among newborns in NICU.

Key words: Hearing loss, Newborn, Gene, GJB2, SLC26A4