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目的 探讨 mt DNA突变与遗传性耳聋的关系 ,以及突变家系对氨基糖甙类抗生素(aminoglycoside antibiotic,Am An)耳毒敏感性差异的原因。方法 调查了 12个非综合征型耳聋家系 ;抽取外周血 ,提取 DNA;PCR扩增线粒体 DNA(mitochondrial DNA,mt DNA)目的片段 ,分别以 Alw2 6 、Apa 及 Xba 限制性内切酶检测 15 5 5 G、32 43G及 744 5 G 点突变 ;行 mt DNA 12 S r RNA、t RNALeu(UUR) 、t RNASer(UCN)及 16 S r RNA基因序列测定。结果 经酶切及测序证实 12个家系具有 mt DNA突变 ,形式为 :15 5 5 G突变家系 10个 ,744 5 G突变家系 2个 ,未发现 32 43G 突变家系。基因测序显示 mt DNA 16 S r RNA基因序列变化形式为 :2 2 30 G点突变、2 2 30 AG插入、2 2 43AG插入及 2 2 30 AA插入突变 ,它们在家族性 Am An耳毒敏感性家系中被发现 ,且呈母系遗传 ;在 Am An不敏感家系中未被发现。结论 单纯 15 5 5 G或 744 5 G突变家系表现为无诱因的渐进性遗传性耳聋或先天性聋 ;15 5 5 G或 744 5 G突变合并 16 S r RNA基因突变者对Am An高度敏感 ,表现为家族性敏感致聋。
Objective To investigate the relationship between mt DNA mutation and hereditary deafness and the reasons for the differences in susceptibility between aminoglycoside antibiotics and aminoglycoside antibiotics (Am An). Methods A total of 12 non-syndromic deafness families were investigated. Peripheral blood samples were collected for DNA extraction. The mitochondrial DNA (mt DNA) fragments were amplified by PCR and detected by restriction endonucleases such as Alw2 6, Apa and Xba, respectively. 5 G, 32 43G and 744 5G point mutations. The mtDNA 12 S rRNA, t RNALeu (UUR), tRNASer (UCN) and 16 S rRNA gene sequences were determined. Results The 12 mt DNA mutants were confirmed by restriction enzyme digestion and DNA sequencing in the form of 10 15 5 5 G mutants and 2 744 744 G mutants. No 32 43G mutant pedigrees were found. Sequence analysis showed that the sequence of mt DNA 16 S rRNA gene was 2 2 30 G point mutation, 2 2 30 AG insertion, 2 2 43AG insertion and 2 2 30 AA insertional mutation, which showed no significant difference in familial Am An ototoxicity The pedigree was found and maternally inherited; it was not found in Am An insensitive pedigrees. Conclusion 1555G or 7445G mutation families showed asymptomatic progressive hereditary deafness or congenital deafness; 1555G or 7445G mutation combined with 16S rRNA gene mutation was highly sensitive to Am An, The performance of familial sensitivity to deafness.