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目的应用基因诊断的方法调查温州地区耳聋患者的分子病因,筛选线粒体12S rRNA基因A1555G突变以及CO1/tRNA~(Ser(UCN))基因的G7444A突变,并探讨突变和药物性耳聋之间的关系。方法对我院收集的150例耳聋患者和80例正常对照进行基因组DNA提取,并针对线粒体12SrRNA和CO1/tRNA~(Ser(UCN))基因进行引物设计,通过PCR扩增目的片段,产物经Sanger直接测序比对线粒体标准序列,检测A1555G和G7444A突变的频率。结果在150例耳聋患者中,存在A1555G突变的患者有10例(6.6%),携带G7444A突变的患者有2例(1.3%),还有15例患者有氨基糖苷类抗生素用药史(10%),而这些突变在正常对照组中均未出现。此外,1例患者同时携带A1555G和G7444A突变,该家系呈现出明显的母系遗传。结论线粒体基因突变和氨基糖苷类抗生素的使用是引起耳聋的重要原因,线粒体A1555G和G7444A突变是耳聋相关的两个致病性位点,在临床上开展线粒体突变筛查对预防药物性耳聋具有重要的意义。
Objective To investigate the molecular pathogenesis of deafness in Wenzhou by gene diagnosis and to screen the mitochondrial 12S rRNA gene A1555G mutation and G7444A mutation of CO1 / tRNA ~ (Ser (UCNN)) gene and explore the relationship between the mutation and drug-induced deafness. Methods Genomic DNA was extracted from 150 cases of deafness patients and 80 normal controls collected from our hospital. The mitochondrial 12SrRNA and CO1 / tRNA ~ (Ser (UCN)) gene were designed and used to amplify the target gene. The products were analyzed by Sanger Direct sequencing of mitochondrial standard sequence, detection A1555G and G7444A mutation frequency. Results Among 150 patients with deafness, 10 (6.6%) had A1555G mutation, 2 (1.3%) had G7444A mutation, and 15 (10%) had aminoglycoside medication history , But these mutations did not appear in the normal control group. In addition, one patient carried both the A1555G and G7444A mutations, which showed a significant maternal inheritance. Conclusion Mitochondrial gene mutations and the use of aminoglycoside antibiotics are important causes of deafness. Mitochondrial A1555G and G7444A mutations are two pathogenic sites associated with deafness. Clinically, screening for mitochondrial mutations is important in preventing drug-induced deafness Meaning.