非综合征型X连锁隐性遗传耳聋家系临床表型及遗传学特征分析  

Clinical and genetic features of a Chinese family with nonsydromic X-linked recessive hearing loss

作　　者：牛志杰[1,2] 冯永[1,2,3] 梅凌云[1,2] 孙捷[1,2,4] 陈红胜[1,2] 贺楚峰[1,2] 刘亚兰[1,2] 王雪萍[1,2] 文杰[1,2] 蒋璐[1,2] Niu Zhijie;Feng Yong;Mei Lingyun;Sun Jie;Cheng Hongsheng;He Chufeng;Liu Yalan;Wang Xueping;Wen Jie;Jiang Lu(Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University,Changsha, 410008, China;Key Laboratory of Otolaryngology Major Disease Research of Hunan Province, Changsha, 410008, China;State Key Laboratory of Medical Genetics, Central South University, Changsha, 410078, China;Department of Otorhinolaryngology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, China)

机构地区：[1]中南大学湘雅医院耳鼻咽喉头颈外科,长沙410008 [2]耳鼻咽喉重大疾病研究湖南省重点实验室,长沙410008 [3]中南大学医学遗传学国家重点实验室,长沙410078 [4]新疆医科大学第一附属医院耳鼻咽喉科,乌鲁木齐830011

出　　处：《中华耳科学杂志》2017年第2期195-200,共6页Chinese Journal of Otology

基　　金：国家自然科学基金项目(Grant No.81300833;81170923;81470705);国家重大科学研究计划项目(Grant No.2014CB541702;2014CB943003);湖南省自然科学基金(Grant No.13JJ4023)共同资助~~

摘　　要：目的分析一个X连锁隐性遗传性耳聋家系的临床特征及遗传学规律。方法通过问卷调查,收集家系成员临床资料,并进行听力学检测、专科检查及全面体查,对临床听力学特征进行分析并绘制遗传图谱,并对先证者进行GJB2、GJB3以及线粒体全序列进行筛查。结果家系成员共28人,其中男性患者5人,分布于第二、三及四代,耳聋发生于0~5岁,迅速进展为双侧对称性中高频下降的重度至极重度感音神经性听力下降,典型听力图表现为特征性的‘U’型或陡降型。4例为语后聋,1例语前聋患儿未能通过新生儿听力筛查。根据系谱图分析,该家系均为男性患病,双亲正常,符合X连锁隐性遗传模式,同时先证者耳聋基因筛查亦为阴性。结论本家系的临床听力学及遗传学特征分析符合X连锁隐性遗传,进一步将通过外显子测序探索该家系耳聋致病基因。Objective To report the clinical and genetic characteristics of a large Chinese pedigree with X-linkedrecessive non-syndromic hearing loss.Methods We used deafness-questionnaires to collect detailed medical history information.Syndromic hearing loss was ruled out via clinical examination,otoscopy and pure-tone audiometry.We plottedthe pedigree based on the genetic and audiology characteristics of this family and screened GJB2,GJB3and mtDNAto exclude well known pathogenic mutations.Results A total of28members were alive in this four-generations family,and5males were found to be hearing-impaired.Most of the patients had moderate to profound sensorineural hearing loss affecting predominantly the middle and high frequencies.One child with apparently pre-lingual hearing loss failedthe newborn hearing screening.One carrier female showed mild hearing loss.The characteristic audiometric configurationwas either a U or a steep sloping pattern.We did not find any causative mutations by screening the three commondeafness genes.Conclusions Pedigree analysis of this family indicates an X-recessive inheritance pattern of hearing impairment,in which affected-male members showed pre-lingual or post-lingual,symmetrical and fast-progressing hearingloss.Whole-exome sequencing is probably needed to identify the disease-causing gene in this family.

关 键 词：家系 X连锁隐性遗传 表型 遗传性耳聋 

分 类 号：R764[医药卫生—耳鼻咽喉科]