【作者】 徐红霞；

【导师】 李彦华；

【作者基本信息】 新疆医科大学 ， 中西医结合临床， 2010， 硕士

【摘要】 目的:利用基因诊断的方法对新疆维汉非综合征型遗传性耳聋患者GJB2基因突变进行分析,研究新疆地区维汉非综合征型遗传性耳聋人群中GJB2基因突变位点、突变频率,并探讨其与肾虚血瘀型之间的关系。方法:收集非综合征型遗传性耳聋患者83例,其中耳聋组维族43例,汉族40例,并对耳聋患者中医辨证分为肾虚血瘀型和非肾虚血瘀型;无耳聋家族史正常人98例,其中维族46例,汉族52例。应用聚合酶链反应(PCR)和正反双向直接测序法对所有受试者进行GJB2基因检测。结果:在耳聋组发现10种碱基改变,其中致病突变4种(235delC、233delC、35delG、71G-A),携带率为10.8%,233-235delC突变共6例,突变率为7.23%,占致病突变总携带率的66.6%。35delG、71G-A突变仅在维族耳聋人群中发现。对照组检测到9种基因碱基改变。79G-A、109G-A和341G-A是各组中常见的多态。196G-A、281A-G和21G-T为新发现突变。汉族GJB2基因的突变率高于维族。肾虚血瘀型患者占所有耳聋患者的38.6%;GJB2基因突变与肾虚血瘀型有关(P<0.05)。结论:新疆地区非综合征型遗传性耳聋患者GJB2基因的致病突变热点为233-235delC,但突变率低于国内其它地区。GJB2基因突变具有种族差异性。新发现的突变和多态丰富了新疆GJB2基因突变及多态性图谱,为深入开展新疆地区耳聋基因筛查及建立基因库奠定了基础。肾虚血瘀型可能是导致新疆地区GJB2基因突变的原因之一。更多还原

【Abstract】 Objective:To detect gene mutations of GJB2 in Uyghur and Han people with non-syndromic hereditary hearing impairment,and to analyze the relationship between gene mutations and kidney asthenia blood stasis type. Method:83 patients of non-syndromic hereditary hearing impairment,including 43 Uyghur and 40 Han,and 98 health adults,including 46 Uyghur and 52 Han,were collected.The patients were differentiated into kidney asthenia blood stasis type and non-kidney asthenia blood stasis type,according to Traditional Chinese Mdecine Differentiation.The GJB2 of patients and normal persons were polymerse chain reaction(PCR),then the PCR products were subjected to automatic DNA sequencing. Results:Ten gene mutations were found in deafness group.The four mutations,235delC、233delC、35delG、71G-A,were disease caused mutation,which have 10.8% detected rate.The quantity of 233-235delC was six,the mutation rate of which is 7.23%,and 66.6% in the totle detected rate of disease caused mutation.71G-A、35delG were found only in the Uyghur deaf-mutes.Nine gene mutations were detected in control group.The mutations of 79G-A、109G-A、341G-A were the most frequent types of polymophism,and 196G-A、281A-G、21G-T were the newly discovered.The GJB2 mutation rate of Han is higher than Uyghur.Kidney asthenia blood stasis type was 38.6% in all of patients.The GJB2 gene mutation is related to kidney asthenia blood stasis(P<0.05). Conclusion:The hot spot of disease caused mutation of GJB2 is 233-235delC in patients with hereditary nonsyndromic hearing impairment in xinjiang region,but mutaional rate of which is lower than other reagions in China. GJB2 gene mutation has racial diversify Newly discovered mutation and polymorphism of GJB2 gene has enriched gene mutation and polymorphism mapping in Chinese population,and laid the foundation for an in-depth genetic screening for deafness and the gene library in Xinjiang region. Kidney asthenia blood stasis type might be one of the reasons which lead to GJB2 gene mutation in the Xinjiang region.更多还原