一个常染色体显性遗传非综合征型聋家系MYO6基因新致病性变异  

Identification of a Novel MYO6 Mutation Associated with Autosomal Dominant Non-syndromic Hearing Loss in a Chinese Family by Whole-exome Sequencing

作　　者：田涛 鲁雅洁[2] 姚俊[2] 曹新[2] 魏钦俊[2] 李琦[1,3] Tian Tao;Lu Yajie;Yao Jun;Cao Xin;Wei Qinjun;Li Qi(Department of Otorhinolaryngology,Nanjing Children’s Hospital,Affiliated to Nanjing Medical University,Nanjing,211008,China)

机构地区：[1]南京医科大学附属儿童医院耳鼻咽喉科,南京211008 [2]南京医科大学基础医学院生物技术系,南京211008 [3]南京大学医学院附属儿童医院耳鼻咽喉科,南京211008

出　　处：《听力学及言语疾病杂志》2019年第4期345-349,共5页Journal of Audiology and Speech Pathology

基　　金：江苏省省级重点研发专项资金(BE2015608);江苏省高层次卫生人才“六个一工程”拔尖人才项目(LGY2018008)联合资助

摘　　要：目的 分析一个常染色体显性非综合征型听力损失家系的听力学特征,应用外显子测序鉴定该家系的致聋原因。方法 通过家系调查、临床听力学和遗传学特征分析,对一个非综合征型听力损失家系的致病原因进行系统研究,对该家系1例听力正常和2例听力损失者进行全外显子组测序确定候选基因,对所有家系成员进行候选基因变异的Sanger测序验证。结果 该家系遗传方式为常染色体显性遗传,表现为双侧对称性的感音神经性听力损失,随着年龄增长听力损失呈进行性加重;通过全外显子组测序鉴定出MYO6基因(DFNA22)新的致病性变异c.622A> G(p.K208E),该变异位点在多物种间保守,并与该家系成员的听力损失表型共分离。结论 在1个常染色体显性非综合征型听力损失家系中通过全外显子组测序发现了MYO6基因新的c.622A>G (p.K208E)致病性变异。Objective To analyze the clinical audiological characters and to identify the causative gene of a Chinese family with nonsyndromic autosomal dominant inherited hearing loss using whole-exome sequencing (WES) approach.Methods The family surveys,clinical audiological characteristics and inheritance patterns of this family were evaluated.Whole exome sequencing was conducted using DNA samples of one normal and two affected members of this family.The candidate mutation was confirmed by Sanger sequencing.Furthermore,multiple in silico analysis (SIFT,Polyphen2,PROVEAN and Mutation Taster) were used to assess the potential pathogenicity of the candidate mutations.Results This Chinese family was characterized by a bilaterally symmetrical and progressively worsening sensorineural hearing loss.A novel causative mutation c.622A>G in MYO6 (DFNA22) resulting in a p.K208E substitution was identified.This mutation co-segregated with the hearing loss phenotype in extended family members was predicted to be pathogenic by SIFT,PolyPhen2,PROVEAN and Mutation Taster.Conclusion In our study,a novel c.622A>G (p.K208E) mutation in MYO6 was identified in a Chinese family affected with DFNA22 by WES and bioinformatics analysis.

关 键 词：全外显子测序 MYO6基因 听力损失 致病变异 Silico分析 

分 类 号：R764.44[医药卫生—耳鼻咽喉科]