耳聋基因诊断技术作为新生儿听力筛查补充手段的应用价值  

Application value of deafness gene diagnosis technique as supplementary means of neonatal hearing screening

作　　者：陈婕 马华 周玉润 孙建乐 黄瑞丽 CHEN Jie;MA Hua;ZHOU Yu-Run(Wenzhou People＇s Hospital,Wenzhou Maternal and Child Health Care Institute,Wenzhou,Zhejiang 325000,China)

机构地区：[1]温州市人民医院温州市妇幼保健所,浙江温州325000 [2]温州医科大学生命科学学院浙江省医学遗传学重点实验室,浙江温州325000

出　　处：《中国妇幼保健》2018年第20期4692-4695,共4页Maternal and Child Health Care of China

基　　金：浙江省人口计划生育科研项目(重点项目)(2014ZDA036);温州医科大学横向科研项目(2014-337)

摘　　要：目的探索耳聋基因诊断技术作为新生儿听力筛查补充手段的应用价值,旨在为新生儿遗传性耳聋病例及其家系提供更科学的再发风险和再生育指导。方法收集2013-2016年温州市鹿城、瑞安、永嘉3个地区经新生儿听力筛查发现、确诊的耳聋病例,从中筛选疑似为遗传性耳聋的29例先证者及其家庭成员77名共同纳入研究,采集病史及家族史、结合听力及影像学检查,提取家系先证者及其家系成员的外周血基因组DNA,对GJB2、SLC26A4和12S rRNA基因的扩增产物进行DNA测序,并进一步对基因序列变异进行生物信息学分析和对比。结果共检出17个耳聋儿家庭携带常见耳聋致病基因突变,2例先证者及其父母均为GJB2纯合突变导致的遗传性耳聋,患儿父母再生育耳聋儿风险为100.00%。4例先证者为GJB2纯合突变导致的遗传性耳聋,其父母均为GJB2突变携带者;1例先证者为SLC26A4纯合突变导致的大前庭水管综合征,其父母均为SLC26A4突变携带者,2例先证者为GJB2 V371(c.109G>A)纯合突变,该位点突变更倾向于致病突变;以上7个耳聋家族患儿父母再生育耳聋儿风险为25.00%。结论耳聋基因诊断技术作为听力筛查后续补充手段有利于明确新生儿疑似遗传性耳聋患儿的遗传病因,能科学客观地为患儿及其家系提供再发风险和再生育咨询与指导。Objective To explore the application value of deafness gene diagnosis technique as supplementary means of neonatal hearing screening,provide more scientific recurrence risk and reproductive guidance for the neonates with hereditary hearing loss and the hearing loss pedigree. Methods The neonates diagnosed as hearing loss definitely by neonatal hearing screening in Lucheng District,Ruian District,Yongjia District of Wenzhou City from 2013 to 2016 were collected,29 propositi suspected of hereditary hearing loss and 77 family members were enrolled in this study. Medical history and family history were collected,hearing examination and imageological examination were performed. Genomic DNA in peripheral blood of propositi and family members were obtained. The amplification products of GJB2,SLC26 A4,and 12 S rRNA genes were analyzed by DNA sequencing. Bioinformatic analysis and comparison were performed for gene sequence variation. Results A total of 17 families with deaf children carrying common deafness genes were detected,two propositi and their parents had hereditary deafness caused by GJB2 homozygous mutation,the risk of deaf neonates born by the parents during subsequent pregnancy was100. 00%. Four propositi were found with hereditary deafness caused by GJB2 homozygous mutation,their parents were carriers of GJB2 mutation. One propositus was found with large vestibular aqueduct syndrome caused by SLC26 A4 homozygous mutation,their parents were carriers of SLC26 A4 mutation. Two propositi were found with GJB2 V371（ c. 109 G〉A） homozygous mutation,the mutation was inclined to be pathogenic mutation. The risk of deaf neonates born by the parents from the above-mentioned seven deaf families during subsequent pregnancy was 25. 00%. Conclusion As a follow-up screening means of hearing screening,deaf gene diagnosis technology is helpful to clarify the hereditary causes of neonates suspected of hereditary deafness,which can scientifically and objectively provide recurrence risk and reproductive counseling and guida

关 键 词：听觉丧失 遗传性耳聋 GJB2基因 SLC26A4基因 线粒体12S rRNA 基因诊断 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]