体外受精胚胎移植婴儿先天性聋临床和基因检测分析  

Clinical and Genetic Characteristics of Infants with Congenital Deafness Born through in Vitro Fertilization and Embryo Transfer

作　　者：胡民强 谭东辉[3] 杨曙[1,2] 朱倩晨 赖若沙[1,2] 谢华平 邓健航 邓忠[3] 谢鼎华[1,2] 伍伟景[1,2] HU Minqiang;TAN Donghui;YANG Shu;ZHU Qianchen;LAI Ruosha;XIE Huaping;DENG Jianhang;DENG Zhong;XIE Dinghua;WU Weijing(Department of Otolaryngology,Second Xiangya Hospital,Central South University,Changsha 410011,China;Institute of Otolology,Central South University,Changsha 410011,China;Affiliated Hospital of Xiangnan University,Chenzhou 423000,China;College of Life Science,Hunan Normal University,Changsha 410081,China;Zhuzhou Hospital Affiliated to Xiangya School of Medicine,Central South University,Zhuzhou 412000,China)

机构地区：[1]中南大学湘雅二医院耳鼻咽喉头颈外科,长沙410011 [2]中南大学耳科研究所,长沙410011 [3]湘南学院附属医院,郴州423000 [4]湖南师范大学生命科学学院,长沙410081 [5]中南大学湘雅医学院附属株洲医院耳鼻咽喉头颈外科,株洲412000

出　　处：《中华耳科学杂志》2023年第2期205-210,共6页Chinese Journal of Otology

摘　　要：目的通过对体外受精胚胎移植(in vitro fertilization and embryo transfer,IVF-ET)技术生育的先天性聋婴儿家庭的患儿及其父母进行基因检测和遗传学分析,从遗传学角度探讨其致聋病因,为预防辅助生殖技术生育听觉缺陷婴儿提供借鉴。方法对三组通过IVF-ET技术生育出先天性聋患儿家庭进行病史和遗传学调查,同时对出生婴儿及其父母进行耳科和全身检查,听力学评估,并通过全外显子组测序(whole exome sequencing,WES)对三组家庭11名成员进行耳聋基因检测和Sanger测序验证所携带耳聋致病基因及突变位点。结果三组家庭通过IVF-ET技术生育5名新生儿,共发生4例先天性感音神经性聋。父母及家族中其他成员均无耳聋表现。WES和Sanger测序结果显示,在三组家庭聋儿及其父母中共发现4种与耳聋相关的基因突变。家庭1突变基因为MYO3A:NM_017433:exon32:c.4462A>G:p.K1488E;MYO15A:NM_016239:exon4:c.3693-2A>G,MYO15A:NM_016239:exon22:c.5638G>A:p.G1880R,该MYO15A基因2个新的突变位点过去未见报道。家庭2突变基因为SLC26A4:NM_000441:exon10:c.1229C>T:p.T410M,SLC26A4:NM_000441:exon19:c.2168A>G:p.H723R。家庭3突变基因为TPO:NM_175721:exon13:c.2404C>T:p.R802W,TPO:NM_175721:exon14:c.2515C>T:p.P839S。结论三组家庭先天性聋患儿均发现已知的耳聋基因突变,其父母携带相同的突变基因,符合遗传规律,其先天性聋与遗传因素有很大相关性。MYO15A基因2个新突变位点的致病性尚待进一步研究。结果提示在应用辅助生育技术时全面耳聋基因筛查的必要性。Objective To report a preliminary clinical and genetic analysis on infants with congenital deafness who were born by in vitro fertilization and embryo transfer(IVF-ET),including their parents,to understand the causes and genetic modes of their deafness,the role of deafness genes and potentially new mutation sites,with the goal of providing clinical evidence for preventing hearing-defects from assisted reproductive technology.Methods Medical history and genetic pedigree survey were completed in three families with children conceived by IVF-ET.Exhaustive ear and general physical examination and audiological assessments were completed on the infants and their parents.Whole exome sequencing(WES)was performed to detect mutation of deafness gene on 11 members of these families.Sanger sequencing was performed to further verify the genetic cause of deafness and mutation sites.Results Congenital sensorineural deafness was found in 4 of the 5 newborns through IVF-ET in the three families.No history of deafness was reported by their parents or in their families.WES and Sanger sequencing analysis showed four types of deafness gene mutations in the infants with congenital sensorineural deafness and their parents.The mutation was located in MYO3A:NM_017433:Exon32:C.4462A>G:P.K1488E,MYO15A:NM_016239:exon4:c.3693-2A>G and MYO15A:NM_016239:exon22:c.5638G>A:P.G1880R in family 1;in SLC26A4:NM_000441:EXON10:C.1229C>T:P.T410M and SLC26A4:NM_000441:exon19:c.2168A>G:P.H723r in family 2;and in TPO:NM_175721:Exon13:C.2404C>:T:P.R802W and TPO:NM_175721:exon14:c.2515C>T:P.P839s in family 3.Conclusion WES and Sanger sequencing showed pathogenic gene mutation sites related to deafness in children with congenital sensorineural hearing loss in the three families,with their parents as carriers of the same mutations in conformation to the law of inheritance,indicating that the congenital deafness observed is likely caused by inheritance rather than assisted reproductive technology.The pathogenicity of two new mutation sites in MYO15A gene needs

关 键 词：先天性聋 感音神经性聋 辅助生殖技术 体外受精胚胎移植 全外显子组测序 

分 类 号：R764[医药卫生—耳鼻咽喉科]