CAJ | 학술논문

目的：通过对11个携带线粒体tRNASer(UCN)G7444A突变的中国汉族非综合征型耳聋家系进行临床和分子遗传学特征等分析评估，探讨线粒体tRNASer(UCN)G7444A突变在母系遗传非综合征型耳聋发生发展中的作用。方法：PCR扩增2650例中国汉族非综合征型耳聋样本的线粒体12SrRNA、线粒体tRNASer(UCN)基因以及GJB2基因。对11个携带线粒体tRNASer(UCN)G7444A突变的中国汉族非综合征型耳聋家系进行听力学检测、耳聋相关热点基因突变检测以及家系资料等综合分析。结果：在2650例中国汉族非综合征型耳聋患者中，14例携带线粒体tRNASer(UCN)G7444A突变，突变率为0.53%。在这11个携带线粒体tRNASer(UCN)G7444A突变的家系中，同时携带线粒体tRNASer(UCN)G7444A突变和线粒体12SrRNAA1555G、12SrRNAC1494T或GJB2c.235delC的家系分别为3、1和2个。临床资料分析表明，这11个中国汉族非综合征型耳聋家系母系成员在听力损失严重程度、发病年龄以及耳聋外显率方面存在较大差异。同时携带线粒体tRNASer(UCN)G7444A突变和线粒体12SrRNAA1555G、C1494T或GJB2c.235delC突变家系的耳聋平均外显率分别为29.4%、42.9%和19.0%。前两者的外显率明显高于只携带线粒体tRNASer(UCN)G7444A突变家系的耳聋平均外显率（为14.0%）。结论：线粒体tRNASer(UCN)G7444A突变可能与线粒体12SrRNAA1555G和C1494T原发突变存在协同作用，共同影响非综合征型耳聋的表型。
목적：통과대11개휴대선립체tRNASer(UCN)G7444A돌변적중국한족비종합정형이롱가계진행림상화분자유전학특정등분석평고，탐토선립체tRNASer(UCN)G7444A돌변재모계유전비종합정형이롱발생발전중적작용。방법：PCR확증2650례중국한족비종합정형이롱양본적선립체12SrRNA、선립체tRNASer(UCN)기인이급GJB2기인。대11개휴대선립체tRNASer(UCN)G7444A돌변적중국한족비종합정형이롱가계진행은역학검측、이롱상관열점기인돌변검측이급가계자료등종합분석。결과：재2650례중국한족비종합정형이롱환자중，14례휴대선립체tRNASer(UCN)G7444A돌변，돌변솔위0.53%。재저11개휴대선립체tRNASer(UCN)G7444A돌변적가계중，동시휴대선립체tRNASer(UCN)G7444A돌변화선립체12SrRNAA1555G、12SrRNAC1494T혹GJB2c.235delC적가계분별위3、1화2개。림상자료분석표명，저11개중국한족비종합정형이롱가계모계성원재은력손실엄중정도、발병년령이급이롱외현솔방면존재교대차이。동시휴대선립체tRNASer(UCN)G7444A돌변화선립체12SrRNAA1555G、C1494T혹GJB2c.235delC돌변가계적이롱평균외현솔분별위29.4%、42.9%화19.0%。전량자적외현솔명현고우지휴대선립체tRNASer(UCN)G7444A돌변가계적이롱평균외현솔（위14.0%）。결론：선립체tRNASer(UCN)G7444A돌변가능여선립체12SrRNAA1555G화C1494T원발돌변존재협동작용，공동영향비종합정형이롱적표형。
Objective: To report the clinical, genetic and molecular characteristics of 11 Han Chinese pedi-grees with mitochondrial tRNASer(UCN) G7444A mutation and explore the role of mitochondrial tRNASer(UCN) G7444A mutation in the development of maternally inherited non-syndromic deafness.Methods: PCR ampli-fication of mitochondrial 12S rRNA, mitochondrial tRNASer(UCN) andGJB2 gene of 2 650 Chinese Han non-syndromic deafness subjects. The proband and family members of 11 Chinese Han pedigrees with mitochondrial tRNASer(UCN) G7444A mutation underwent audiological testing, deafness associated mutational hot spots screen-ing and pedigree assessment.Results: Among the 2 650 Han Chinese non-syndromic deafness subjects, 22 pa-tients belonging to 11 pedigrees carried mitochondrial tRNASer(UCN) G7444A mutation, account for 0.7%. Num-ber of pedigree carry both mitochondrial tRNASer(UCN) G7444A mutation and mitochondrial 12S rRNA A1555G, mitochondrial 12S rRNA C1494T orGJB2 c.235delC mutation were 3, 1, 2 respectively. Clinical data showed that there were huge difference in the severity of hearing loss, age of onset and penetrance among these 11 Chi-nese Han non-syndromic deafness pedigrees. The average penetrance of these pedigrees carrying mitochondrial tRNASer(UCN) G7444A mutation and mitochondrial 12S rRNA A1555G, C1494T orGJB2 c.235delC mutation were 29.4%, 42.9% and 19.0% respectively. The average penetrance of 4 pedigrees carrying the mitochondrial tRNASer(UCN) G7444A mutation and mitochondrial 12S rRNA A1555G or C1494T mutation is signiifcantly higher than that of carry mitochondrial tRNASer(UCN) G7444A mutation, it was 14.0%.Conclusion: Mitochondrial tRNASer(UCN) G7444A mutation and mitochondrial 12S rRNA A1555G or C1494T mutations may co-modulate the variable penetrance and expressivity of deafness among these Han Chinese non-syndromic pedigrees.