线粒体DNA突变致聋家系检测及单倍型分析

Mitochondrial DNA 1555G mutation detection and haplotype analysis in pedigrees with deafness

目的探讨母系遗传氨基糖甙类抗生素诱发致聋家系的线粒体DNA突变情况及其单倍型背景。方法收集贵州遵义地区6个母系遗传非综合征性耳聋家系的临床资料及血液样本,经PCR-RFLP(polymerase chain reaction-restriction fragment length polymorphism,聚合酶链反应-限制性片段长度多态)及测序技术检测线粒体DNA1555G突变,并通过对各家系线粒体DNA高变区序列测定及编码区限制性片段多态性分析以划分单倍型类群。结果经酶切及测序证实其中4个家系存在线粒体DNA1555G突变,分别属于A、D6、G及M单倍型。结论该地区线粒体DNA1555G突变引起氨基糖甙类抗生素高度敏感致聋的家系发生率较高,线粒体DNA1555G突变致聋家系呈现不同的线粒体单倍型类型。

Objective To investigate the mtDNA 1555G mutation in maternal inherited aminoglycoside-induced hearing loss pedigrees.Methods Clinical histories and blood samples were collected from 6 families with maternal inherited non-syndromic hearing impairment in Zunyi,Guizhou province.PCR-RFLP and DNA sequencing were carried out to detect the mtDNA 1555G mutation.With the aid of the information extracted from control-region hypervariable segments I and II as well as necessary coding-region segments,phylogenetic status of all mtDNAs under study were categorized into various defined haplogroups.Results The mtDNA 1555G mutation was detected in 4 pedigrees,which were assigned into haplogroups A,D6,G and M,respetively.Conclusion The prevalence of aminoglycoside-induced deafness associated with the mtDNA 1555G mutation in Zunyi is comparatively high,and the pedigrees belong to diverse haplogroups.The testing can provide information for gene diagnosis and genetic counseling,and help improve the safety of aminoglycoside antibiotic therapy.