连接蛋白基因突变在散发耳聋人群中的病因学分析  

The roles of connexin genes in sporadic hearing loss population

作　　者：李庆忠[1] 王秋菊[2] 迟放鲁[3] 李丽娜[2] 赵亚丽[2] 袁虎[2] 韩东一[2] 

机构地区：[1]解放军总医院耳鼻咽喉头颈外科 耳鼻咽喉研究所 复旦大学附属眼耳鼻喉医院耳鼻咽喉科,北京100853 [2]解放军总医院耳鼻咽喉头颈外科 耳鼻咽喉研究所,北京100853 [3]复旦大学附属眼耳鼻喉医院耳鼻咽喉科

出　　处：《中华医学杂志》2007年第16期1097-1101,共5页National Medical Journal of China

基　　金：国家"863"计划基金(2006AA02Z181);国家自然科学基金(30470956;30572016;30672310);高等学校全国优秀博士学位论文作者专项基金资(200463)

摘　　要：目的探讨连接蛋白基因突变在散发耳聋患者发病机制中的意义,绘制北方耳聋人群连接蛋白基因突变谱。方法利用遗传性耳聋遗传资源收集网络所收集的遗传性聋病资源,在耳聋人群中进行系列连接蛋白基因(GJB2、GJB3和 GJB6基因)突变检测。PCR 扩增连接蛋白基因编码区,应用直接测序法进行突变检测,并对实验结果进行整理、生物信息学和统计学分析。结果 (1)研究对象为214例散发聋病患者,包括语前聋66例,语后聋94例,听神经病32例和大前庭水管综合征(EVAS)22例。正常听力者86名作为对照。(2)在本组中共检测到各种连接蛋白基因序列改变16种(其中 GJB2基因9种、GJB3基因6种、GJB6基因1种);携带各种连接蛋白基因序列改变的患者共有157例,占73.36%(157/214);其中有34例携带致病突变,占15.89%(34/214)明显高于对照组(1.18%。x^2=12.9072,P=0.000)。在语前聋组中 GJB2-235 delC 发生率最高为16.67%。结论通过本研究发现,在北方汉族耳聋人群中 GJB2基因的235 delC 突变所占比例最高,是语前听力损失患者中的主要病因,而 GJB2基因的35 delG 和 GJB6基因的大片段缺失[Δ(GJB6/D13S1830)]在中国耳聋人群中并不常见。Objective To investigate the roles of connexin genes in Chinese population. Methods Peripheral blood samples were collected from 214 patients with hearing loss, 160 with sensorineural hearing loss （66 with prelingual hearing loss and 94 with posdingual hearing loss）, 32 with auditory neuropathy, and 22 with enlarged vestibular aqueduct syndrome （EVAS）, 110 males and 104 females, all from 14 provinces north of the Yangtze River, all of Han nationality, and 86 normal controls. PCR and sequencing of the PCR products were used to screen 3 connexin genes ： GJB2, GJB3, and GJB6. Results The frequency of connexin gene sequence variant was 73.36% （157/214） , higher than that of the controls （60.05% , 42/86）. 34 of the 157 patients carried pathogenic mutations （ 15.89% ）. The frequency of 235delC deletion was 16.67% among patients with prelingual hearing loss （ 11/66 ）. Six known polymorphisms and six new mutations were found in these patients. Conclusion The pathogenic mutations of the patients with hearing loss are distributed quite differently between the patients and normal persons. The genetic variants GJB2 235delG and GJB6-△ （GJB6/D13S1830） were not common. Relevant information is helpful in early diagnosis of heating loss in Chinese population.

关 键 词：聋 突变 连接蛋白类 GJB2 

分 类 号：R764[医药卫生—耳鼻咽喉科]