三个内耳不全分隔Ⅲ型家系的表型特征和突变分析  

Inner Ear Incomplete Partition TypeⅢ:Mutation Analysis of the POU3F4 Gene in Three Families

作　　者：冯海锋 赵一馨 翟荣群 曾焙枰 汤文学 陈蓓[1] 卢伟[1] FENG Haifeng;ZHAO Yixin;ZHAI Rongqun;ZENG Beiping;TANG Wenxue;CHEN Bei;LU Wei(Department of Otorhinolaryngology,First Affiliated Hospital of Zhengzhou University,Zhengzhou,450052;Department of Otolaryngology,Head and Neck Surgery,Peking University People's Hospital,Beijing,100044;Center of Precision Medicine,Academy of Medical Science,Zhengzhou University,Zhengzhou,450052;Center of Applied Precision Medicine,Second Affiliated Hospital of Zhengzhou University,Zhengzhou,450000)

机构地区：[1]郑州大学第一附属医院耳鼻喉医院耳科,郑州450052 [2]北京大学人民医院耳鼻咽喉头颈外科,北京100044 [3]郑州大学医学科学院精准医学中心,郑州450052 [4]郑州大学第二附属医院精准医学研究应用中心,郑州450000

出　　处：《中华耳科学杂志》2023年第1期64-68,共5页Chinese Journal of Otology

基　　金：河南省高等院校重点科研项目(22A320026)。

摘　　要：目的采用二代高通量测序技术为3例内耳不全分隔Ⅲ型(IP-Ⅲ)耳聋患者提供病因诊断并探讨IP-Ⅲ畸形的临床特征、干预措施及效果。方法进行全面体格检查、听力学和颞骨影像学检查。获取知情同意后,抽取受试者外周血进行全外显子组测序和Sanger测序验证。结果3例先证者均患有先天性重度-极重度耳聋。颞骨HRCT显示耳蜗蜗轴缺失、阶间分隔存在,内听道基底部膨大,耳蜗底转与内听道缺少骨性分隔且相互交通。全外显子组测序发现2个POU3F4基因截断突变(c.985C>T,c.80dup;NM_000307.5)和一个POU3F4基因缺失突变。助听器对先证者3听力重建有效,先证者1和2人工耳蜗植入后效果不满意。结论3例IP-Ⅲ型患者的耳聋和特征性内耳畸形由POU3F4基因突变造成,本文新突变的报道扩展了POU3F4突变谱并有利于家系遗传咨询。Objective Inner ear incomplete partition typeⅢ(IP-Ⅲ)is an X-linked recessive non-syndromic deafness disease caused by mutations in the POU3F4 gene.The purpose of this study is to provide an etiological diagnosis for three unrelated patients with IP-Ⅲwith a discussion on its clinical manifestations,interventions and prognosis.Methods Detailed physical examination,audiological and radiological tests were performed on the three probands.Peripheral blood was obtained for DNA extraction after informed consent was obtained.Their DNA was subjected to whole-exome sequencing to screen POU3F4 mutations.Candidate variants were verified using Sanger sequencing and interpreted following the American College of Medical Genetics and Genomics guidelines for interpreting sequence variants.Results The three affected males presented with severe-to-profound deafness diagnosed in infancy.High-resolution computerized tomography indicated absence of the cochlear modulus,presence of interscalar septa,along with dilatation of the internal auditory canal(IAC),and missing bony separation between the basal turn of the cochlea and the IAC.Genetic testing identified three POU3F4 mutations(NM_000307.5):c.985C>T,c.80dup,and entire gene deletion.Hearing aids was used to facilitate hearing rehabilitation in proband 3,while cochlear implantation(CI)was used for hearing gains in probands 1 and 2 with unsuccessful outcomes.Conclusion The etiology of IP-Ⅲin this study was attributed to POU3F4 mutations.The novel mutations identified in this study supplement the mutation spectrum of the POU3F4 gene and facilitated genetic counseling for the three families.

关 键 词：内耳不全分隔Ⅲ型 POU3F4基因 全外显子组测序 人工耳蜗 

分 类 号：R764[医药卫生—耳鼻咽喉科]