4个非综合征耳聋家系中检出线粒体COI和COII基因的新变异

Novel mutations and polymorphisms of mitochondrial DNA COI and COII gene in four pedigrees with non-syndromic hearing impairment

目的报道4个疑有母系遗传特征的中国非综合征耳聋家系的线粒体分子遗传学特征。方法应用限制性内切酶酶切和直接测序技术对先证者的线粒体基因序列进行分析,同时收集患者的相关临床资料。结果在2个非综合征耳聋家系的先证者中发现线粒体COⅠ和COⅡ基因上两个新变异形式(7250A>G和7774G>A)均为沉默突变(Thr→Thr和Thr→Thr),而位于COⅠ基因上的7196C>A(Leu→Leu)、7319T>C(Ile→Ile)和COⅡ基因上的7660A>G(Asp→Asp)为国外及汉族群体中已报道的3个多态性位点,其中COⅠ基因两个多态性位点为首次在畲族耳聋遗传家系中报道。这些突变或多态没有产生错义氨基酸,可能通过基因调控机制使tRNA代谢或线粒体功能产生缺陷,或者对氨基糖甙类药物易感而致聋。同时,在家系中未发现GJB2、MTO1基因及其他线粒体基因突变。结论 mtDNA7250A>G和7774G>A为汉族耳聋家系中新发现的线粒体基因突变形式,而mtDNA7196C>A和7319T>C是首次在畲族耳聋遗传家系中报道。

Objective To analyze mtDNA mutations or polymorphism in four typical Chinese probands with non-syndromic sensorineural hearing loss （NSHL）. Methods PCR-RFLP and DNA sequencing were used to detect and validate the mutation or polymorphism in mitochondrial DNA. Results There were two new mutations in the mitoehondria CO Ⅰ and CO Ⅱ gene （A7250G and G7774A）. Both of them were silent mutations with the amino acid change of Thr→Thr.Meanwhile three polymorphisms： C7196A （Leu→Leu）, T7319C（Ile→Ile） in the CO I gene and A7660G （Asp →Asp） in the CO II gene, which have been reported in the Han population, were also identified. There were no MTO1 gene, GJB2 gene or other mitochondrial gene mutations in the four pedigrees. Conclusion This is the first time that C7196A andT7319C in the CO I gene are reported in deafness pedigrees of the ethnic She population which is a minority ethnic group in China. Although all of the mutations or polymorphisms did not make amino acid change, it may disturb the gene regulat- ed mechanisms, resulting in a defect in tRNA metabolic or mitochondrial function or sensitivity to aminoglycosides antibiotic.