非综合征型听神经病患者OTOF基因筛查研究  

OTOF Gene Mutation Screening in Patients with Non-syndromic Auditory Neuropathy

作　　者：梁鹏飞 王锦玲 王剑 王淑娟 邱建华 查定军 LIANG Pengfei;WANG Jinling;WANG Jian;WANG Shujuan;QIU Jianhua;ZHA Dingjun(Department of Otolaryngology and Head and Neck Surgery,Xijing Hospital,Air Force Military Medical University)

机构地区：[1]空军军医大学西京医院耳鼻咽喉头颈外科

出　　处：《中华耳科学杂志》2019年第1期35-39,共5页Chinese Journal of Otology

基　　金：国家重点基础研究发展规划项目(2014CB541700);国家自然科学基金项目(81870732);国家自然科学基金项目(81470695);陕西省科技重点项目(2018PT-01);陕西省科技重点项目(2017ZDXM-SF-061);西京助推-先进学科建设项目(XJZT14X07)联合资助~~

摘　　要：目的对非综合征型听神经病患者进行OTOF基因突变筛查,了解中国听神经病患者中OTOF基因的突变频谱。方法选取西京医院耳鼻咽喉头颈外科门诊2009-2018年确诊的听神经病患者248名以及听力正常的健康志愿者100名,采集外周静脉血提取全基因组DNA。针对OTOF基因全部48个外显子设计引物,采用聚合酶链式反应扩增外显子及其侧翼序列进行Sanger测序,应用Seqman软件与标准序列进行比对。结果 248例听神经病患者中共检出9种可能致病的变异方式,包括7种错义突变和2种剪切位置的变化。同时,检出4种已有文献报道的多态性改变。所有变异方式在健康志愿者中均未发现。结论可能致病突变集中于Exon40、Intron32、Exon12、Ex?on18、Exon24、Intron28和Exon7中,在门诊耳聋患者或者听力正常人群中,优先开展以上外显子的筛查。OTOF基因突变并不是患者唯一的致病原因,还应进行其他相关基因的筛查。Objective To investigate mutation spectrum of the OTOF gene among Chinese patients with auditory neuropathy.Methods Genomic DNA samples were extracted from peripheral venous blood in 248 outpatients diagnosed with non-syndromic auditory neuropathy at Xijing Hospital from 2009 to 2018 and 100 healthy unrelated individuals with normal hearing.PCR primers were designed to amplify the whole 48 exons and their flanking sequences.The amplified target fragments were sequenced directly.The Seqman software was used analyze the sequence data.Results In this study,we found 9 probable pathogenic mutations,including 7 missense mutations and 2 splice-site changes.Meanwhile,4 reported polymorphic changes were also detected.None of the variants was found in the 100 healthy subjects.Conclusion The probable pathogenic mutations appear to be concentrated in Exon40,Intron32,Exon12,Exon18,Exon24,Intron28 and Exon7.OTOF screening of these exons are therefore preferred in patients with auditory neuropathy or other types of hearing loss.Towards the findings,OTOF singe allele mutations are not the only cause of auditory neuropathy and other related genes should also be screened.

关 键 词：听神经病 OTOF基因 基因筛查 

分 类 号：R764[医药卫生—耳鼻咽喉科]