连接蛋白基因突变在散发耳聋人群中的病因学分析

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—235delC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235delC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35delG和GJB6基因的大片段缺失△（GJB6／D13S1830）]在中国耳聋人群中并不常见。

The roles of connexin genes in sporadic hearing loss population

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 postlingual 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-Delta (GJB6/D13S1830) were not common. Relevant information is helpful in early diagnosis of hearing loss in Chinese population.