186例耳聋患者线粒体DNA 12S rRNA基因筛查及家系分析

Screening and pedigree analysis of mitochondrial DNA 12S rRNA gene in children with non-syndromatic deafness

目的探讨耳聋患者线粒体DNA(mtDNA)12S rRNA基因突变频率以及相关突变位点对药物性耳聋表型表达的影响。方法选取2016至2018年温州特殊教育学校186例非综合征耳聋患者作为研究对象,应用Sanger测序法对mtDNA 12S rRNA进行测序,并进行临床资料分析和家系评估。结果186例耳聋患者中37例明确有使用氨基糖甙类药物史,占19.9%。通过mtDNA 12S rRNA检测,筛选出变异类型16种,其中保守指数(CI)>75%的变异位点包括827A>G、1095 T>C、1107 T>C、1382 A>C、1431 G>A、1541 T>C、1555 A>G。其中明确与药物性耳聋相关的1555A>G位点突变10例,突变率为5.4%,家系评估显示平均耳聋外显率为26.8%。结论通过对非综合征耳聋患者mtDNA 12S rRNA筛查,并运用遗传手段预判药物耳毒性风险,明确部分药物性耳聋患者的病因,可提高患者用药安全性,通过遗传咨询可为下一代防聋治聋提供依据。

Objective To investigate the frequency of mitochondrial DNA 12S rRNA gene mutations in children with non-syndromatic deafness.Methods Clinical data of 186 children with non-syndromatic deafness in Wenzhou Special Education School were collected from 2016 to 2018.The Sanger sequencing for mitochondrial DNA 12S rRNA and pedigree analysis were performed.Results Among 186 cases of non-syndromatic deafness,37 had definite history of aminoglychosides drug use(19.9%).Sixteen types of variation were identified by 12S rRNA gene analysis.Conservative analysis showed that mutations of CI>75%included 827A>G,1095 T>C,1107 T>C,1382 A>C,1431 G>A,1541 T>C,1555 A>G.Ten cases with 1555A>G mutation were clearly related to drug-induced deafness(5.4%),and pedigree evaluations showed that the average deafness penetrance rate was 26.8%.Conclusion Screening mtDNA 12S rRNA mutations in children with non-syndrome deafness can predict the risk of drug ototoxicity,and provide the basis for prevention of drug-induced deafness in the next generation through genetic counseling.