遗传性耳聋资源收集保存及基因定位克隆  

Hereditary hearing impairment: pedlgrees collecting, gene mapping, positional cloning and epidemiology studies in Chinese population

作　　者：王秋菊[1,2] 韩东一[1] 郭玉芬[3] 李庆忠[4] 袁虎[1] 赵亚丽[1] 兰兰[1] 关静[3] 徐百成[3] 郭维维[1] 纵亮[1] 韩明鲲[1] 王大勇[1] 陈之慧[1] 刘穹[1] 杨伟炎[1] 沈岩[2] 

机构地区：[1]解放军总医院耳鼻咽喉头颈外科,解放军耳鼻咽喉研究所,北京100853 [2]国家人类基因组北方中心,甘肃兰州730030 [3]兰州大学第二医院耳鼻咽喉头颈外科,上海200031 [4]复旦大学附属眼耳鼻喉科医院耳鼻咽喉科,北京100176

出　　处：《中国耳鼻咽喉头颈外科》2006年第10期661-665,共5页Chinese Archives of Otolaryngology-Head and Neck Surgery

基　　金：国家自然科学基金面上项目(30370782;30470956;30572016);北京市重大科技项目(H020220020610);高等学校全国优秀博士学位论文作者专项资金资助项目(200463);军队"十一五"杰出人才项目(06J018)联合资助

摘　　要：目的建立聋病遗传资源收集网络,着重收集具有中国特色的聋病遗传资源,进行聋病基因定位克隆及相关的分子流行病学研究。方法通过遗传资源收集网络进行聋病遗传资源的收集,建立资源库进行遗传资源的表型鉴定和分析。应用微卫星标记的连锁分析及候选基因法进行家系的基因定位克隆和分子流行病学研究。结果共收集到含有多种耳聋表型的大小家系2071个,其中涵盖了单基因病孟德尔遗传的全部遗传方式:包括X-连锁遗传家系2个,Y-连锁遗传家系1个(命名为DFNY1基因座)、常染色体显性遗传性耳聋大家系12个(完成了基因定位5个)、常染色体隐性遗传性耳聋核心家系619个以及线粒体突变母系遗传性耳聋家系76个;大前庭水管综合征163例;听神经病108例;不明原因感音神经性耳聋478例;西北地区聋哑学校聋哑患者612例。对1489例散发患者进行了线粒体基因12S rRNA 1555G,缝隙连接蛋白基因(GJB2,GJB3和GJB6)以及SLC26A4基因的突变筛查与分析。其中西北地区612例聋哑人群中发现27．92％患者分别存在三个基因的突变,mtDNAA1555G平均阳性率为9．15％,GJB2为9．97％,SLC26A4为8．8％。结论遗传性听力损失是非常常见的耳聋疾病,其发病率超出原有的预测。基于大家系的基因定位研究有望发现新的基因座位及新的基因突变。分子流行病学研究发现遗传因素在先天性聋和学语后听力损失中的作用强于环境因素,并发现中国人群具有耳聋基因的高发病率和特异的突变图谱。OBJECTIVE The purpose of the study is to establish standard protocols and a network for collecting genetic resources of hearing loss in China for further mapping the hereditary hearing impairment genes and performing the molecular epidemiology studies in Chinese population. METHODS The protocols performed in the studies are approved by Chinese PLA General Hospital Institution Review Board of the Ethics Committee. All hearing loss patients and their relatives involved in the studies are informed consent. DNA samples, immortalized cell lines as well as the detail clinical audiological information are subsequently collected and characterized according to the clinic phenotypes. Linkage analysis in X chromosome and autosomes with micro-satellite markers are performed in the large families for gene mapping and positional cloning. Candidate approach is carried out for epidemiology studies. RESULTS 2071 Chinese hearing loss families have been characterized in our study which included two X-linked, one Y-linked, 12 large autosomal dominant hearing loss families, 619 simplex autosomal recessive hereditary hearing loss families; 76 mitochondrial inheritance families; 163 cases enlarged vestibular aqueducts syndrome; 108 cases with auditory neuropathy; 478 sporadic sensorineural hearing loss cases as well as 612 deafmutism cases from deaf-mute school in northwest territory. Through linkage analysis, one of the two X-linked families successfully found a novel mutation in POU3F4 gene, another X-linked family was mapped to a novel locus, nominated AUNXl（auditory neuropathy, X-linked locus1）; the rare large Y-linked family mapped to DFNY1 locus; five of the 12 autosomal dominant families were mapped in the autosomes. 1489 sporadic patients were performed on mtDNA 12S rRNA 1555G, GJB2 as well as SLC26A4 gene screening and mutation analysis. 27.92 % of the 612 patients in northwest territory were found to be caused by the three genes mutations and the prevalence was 9.15 % in mtDNAA1555G, 9.97 % in GJB2 and 8.8 % in SLC26A4 ge

关 键 词：聋 基因 突变 DFNY1基因座 

分 类 号：R764.43[医药卫生—耳鼻咽喉科]