1007例新生儿听力筛查及耳聋基因测序结果分析  

Analysis of Hearing Screening and Deafness Gene Sequencing Results in 1007 Newborns

作　　者：黄卫彤[1] 刘锦嵩 王宗杰[1] 廖旺[1] 张峰 朱茂灵[1] 鄢盛恺 HUANG Weitong;LIU Jinsong;WANG Zongjie;LIAO Wang;ZHANG Feng;ZHU Maoling;YAN Shengkai(Nanning Maternal and Child Healthcare Hospital,Nanning 53001,China;School of Laboratory Medicine,Zunyi Medical University,Zunyi 563006,China;Department of Laboratory Medicine,Affiliated Hospital of Zunyi Medical University,Zunyi,563003,China;Beijing Institute of Genomics,Chinese Academy of Sciences,Beijing 100101)

机构地区：[1]南宁市妇幼保健院,南宁530011 [2]遵义医科大学附属医院检验科,遵义563003 [3]遵义医科大学检验医学院,遵义563006 [4]中国科学院北京基因组学研究所,北京100101

出　　处：《中华耳科学杂志》2022年第6期873-878,共6页Chinese Journal of Otology

基　　金：南宁市科学研究与技术开发重点研发计划基金资助(20173017-6)、国家自然科学基金(82070916)。

摘　　要：目的研究南宁市新生儿耳聋基因突变情况,评估新生儿听力筛查准确性,探讨突变位点与听力损失的关系。方法采用耳声发射和自动听性脑干诱发电位反应对出生于2016年1月-2018年12月的17000例新生儿进行听力初筛、复筛及确诊检查,针对GJB2、GJB3、SLC26A4基因对1007例听力初筛未通过的新生儿进行靶向捕获高通量测序,结合生物信息学分析,明确突变位点致病性。结果1007例初筛未过的新生儿中,确诊听力损失78例,355例(35.25%,355/1007)检出突变耳聋基因,其中237例检出12种“致病的”或“可能致病的”突变位点,78例检出新错义突变位点(GJB2:c.217C>A、c.316T>G、c.676G>T;SLC26A4:c.739T>C),13例听力确诊正常者检出11种非编码区突变。GJB2、GJB3、SLC26A4基因的突变携带率分别为1.75%、0.66%、0.36%。GJB2:c.79G>A和GJB3:c.357C>T、c.341A>G、c.608T>C的等位基因频率符合哈迪-温伯格遗传平衡定律,GJB2:c.79G>A(Z=3.082;P<0.01)、c.109G>A(Z=10.670;P<O.O1)和GJB3:c.357C>T(Z=2.902;P<0.01)、c.341A>G(Z=2.798;P<0.001)与听力损失的关联具有统计学意义。结论本研究证实GJB2 c.109G>A是南宁市新生儿携带率最高的耳聋基因突变位点。结合听力和基因检测是临床早期干预非综合征型听力损失更有效的策略。Objective To understand common deafness genes mutation in newborns in Nanning,their relationship with hearing loss,and reliability of newborn hearing screening.Methods Hearing screening using otoacoustic emissions(OAE)coupled with automated auditory brainstem responses(AABR)was administered in 17,000 newborns from January 2016 to December 2018.Targeted high-throughput sequencing of the GJB2,GJB3 and SLC26A4 genes was performed on 1,007 newborns who failed the hearing screening.The pathogenicity of mutation was analyzed in conjunction with bioinformatics.Results Among the 1,007 newborns who failed the hearing screening,355(35.25%)were found to carry at least one mutation site on the three deafness genes,with 237 carrying 12"pathogenic"or"likely pathogenic"mutations and 78 carrying novel missense mutations(GJB2:c.217C>A、c.316T>G、c.676G>T、SLC26A4:c.739T>C),and a diagnosis of hearing loss was confirmed in 78.The gene carrier frequency of GJB2,GJB3,and SLC26A4 was 1.75%,0.66%and 0.36%,respectively.Statistically,the allele frequencies of GJB2:c.79G>A,GJB3:c.357C>T,c.341A>G and c.608T>C were in Hardy-Weinberg's equilibrium,with significant association between genotypes and phenotype for GJB2:c.79G>A(Z=3.082;P<0.01),c.109G>A(Z=10.670;P<0.01),GJB3:c.357C>T(Z=2.902;P<0.01)and c.341A>G(Z=2.798;P<0.001).Conclusion This study confirmed that the carrier rate of GJB2c.109G>A was the highest in Nanning.Combining hearing and genetic screening can increase the detection rate of neonatal deafness and play an essential role in the early clinical intervention of non-syndromic hearing loss.

关 键 词：遗传性听力损失 新生儿 耳聋基因 听力筛查 靶向捕获高通量测序 

分 类 号：R764[医药卫生—耳鼻咽喉科]