23项新生儿耳聋基因筛查突变频谱分析  

Mutation spectrum analysis of 23-site chip neonatal deafness genetic screening

作　　者：阮宇[1] 程晓华[1] 张伟[1] 赵丽萍[1] 谢锦各 文铖 李悦 邓琳 黄丽辉[1] RUAN Yu;CHENG Xiaohua;ZHANG Wei;ZHAO Liping;XIE Jinge;WEN Cheng;LI Yue;DENG Lin;HUANG Lihui(Department of Otolaryngology Head and Neck Surgery,Beijing Tongren Hospital,Capital Medical University,Beijing Institute of Otolaryngology,Key Laboratory of Otolaryngology Head and Neck Surgery,Ministry of Education,Beijing,100005,China)

机构地区：[1]首都医科大学附属北京同仁医院耳鼻咽喉头颈外科、北京市耳鼻咽喉科研究所、耳鼻咽喉头颈科学教育部重点实验室(首都医科大学),北京100005

出　　处：《临床耳鼻咽喉头颈外科杂志》2024年第4期267-272,共6页Journal of Clinical Otorhinolaryngology Head And Neck Surgery

基　　金：首都卫生发展科研专项自主创新项目(No:首发2022-2-1092);国家自然科学基金面上项目(No:82071064)。

摘　　要：目的:分析北京市23项新生儿耳聋基因筛查的突变频谱,为遗传咨询及临床诊疗提供依据。方法;研究对象为2022年12月-2023年6月在首都医科大学附属北京同仁医院接受23项耳聋基因筛查的新生儿21006例。23项耳聋基因筛查包括4个基因23个位点:GJB2基因(c.35delG、c.176_191del16、c.235delC、c.299_300delAT、c.109G>A、c.257C>G、c.512insAACG、c.427C>T、c.35insG)、SLC26A4基因(c.919-2A>G、c.2168A>G、c.1174A>T、c.1226G>A、c.1229C>T、c.1975G>C、c.2027T>A、c.589G>A、c.1707+5G>A、c.917insG、c.281C>T)、线粒体12SrRNA基因(m.1555A>G、m.1494C>T)和GJB3基因(c.538C>T)。分析各基因位点的突变率及等位基因突变频率。结果:21006例中,耳聋基因筛查未通过率11.516%(2419/21006)。4个基因中GJB2基因突变率最高,为9.097%(1911/21006),其次分别为SLC26A4基因2.123%(446/21006)、GJB3基因0.362%(76/21006)及线粒体12SrRNA基因0.176%(37/21006)。GJB2基因中,c.109G>A和c.235delC突变率最高,分别为6.579%(1382/21006)和1.795%(377/21006)。SLC26A4基因中,c.919-2A>G和c.2168A>G突变率最高,分别为1.423%(299/21006)和0.233%(49/21006)。等位基因突变频率,GJB2基因c.109G>A最高,为3.359%(1411/42012),其次为GJB2基因c.235delC,0.897%(377/42012)及SLC26A4基因c.919-2A>G,0.719%(302/42012)。结论:北京市23项新生儿耳聋基因筛查提示,GJB2基因c.109G>A突变率和等位基因突变频率最高,值得临床重视。本研究丰富了23项新生儿耳聋基因筛查突变频谱的流行病学资料,可为临床提供依据。Objective:To analyze the mutation spectrum of 23-site chip newborn deafness genetic screening in Beijing,and to provide basis for genetic counseling and clinical diagnosis and treatment.Methods: The study included 21006 babies born in Beijing from December 2022 to June 2023.All subjects underwent newborn deafness genetic screening in Beijing Tongren Hospital,covering 23 variants in 4 genes,the GJB2 gene(c.35delG,c.176_191del16,c.235delC,c.299_300delAT,c.109G>A,c.257C>G,c.512insAACG,c.427C>T,c.35insG),SLC26A4 gene(c.919-2A>G,c.2168A>G,c.1174A>T,c.1226G>A,c.1229C>T,c.1975G>C,c.2027T>A,c.589G>A,c.1707+5G>A,c.917insG,c.281C>T),Mt12SrRNA(m.1555A>G,m.1494C>T)and GJB3 gene(c.538C>T).The mutation detection rate and allele frequency were analyzed.Results: The overall mutation detection rate was 11.516%(2419/21006),with the GJB2 gene being the most frequently involved at 9.097%(1911/21006),followed by the SLC26A4 gene at 2.123%(446/21006),the GJB3 gene at 0.362%(76/21006)and Mt12SrRNA at 0.176%(37/21006).Among the GJB2 genes,c.109G>A and c.235delC mutation detection rates were the highest,with 6.579%(1382/21006)and 1.795%(377/21006),respectively.Of the SLC26A4 genes,c.919-2A>G and c.2168A>G had the highest mutation rates of 1.423%(299/21006)and 0.233%(49/21106),respectively.Regarding the allele frequency,GJB2 c.109G>A was the most common variant with an allele frequency of 3.359%(1411/42012),followed by the GJB2 c.235delC at 0.897%(377/42012)and the SLC26A4 c.919-2A>G at 0.719%(302/42012).Conclusion: 23-site chip newborn deafness genetic screening in Beijing showed that GJB2 c.109G>A mutation detection rate and allele frequency were the highest.This study has enriched the epidemiological data of 23-site chip genetic screening mutation profiles for neonatal deafness,which can provide evidence for clinical practice.

关 键 词：新生儿 耳聋基因 突变率 等位基因突变频率 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]