Mitochondrial diseases are a heterogeneous group of inherited disorders character-ized by mitochondrial dysfunction,and these diseases are often severe or even fatal.Mito-chondrial diseases are often caused by mitocho...Mitochondrial diseases are a heterogeneous group of inherited disorders character-ized by mitochondrial dysfunction,and these diseases are often severe or even fatal.Mito-chondrial diseases are often caused by mitochondrial DNA mutations.Currently,there is no curative treatment for patients with pathogenic mitochondrial DNA mutations.With the rapid development of traditional gene editing technologies,such as zinc finger nucleases and tran-scription activator-like effector nucleases methods,there has been a search for a mitochon-drial gene editing technology that can edit mutated mitochondrial DNA;however,there are still some problems hindering the application of these methods.The discovery of the DddA-derived cytosine base editor has provided hope for mitochondrial gene editing.In this paper,we will review the progress in the research on several mitochondrial gene editing technologies with the hope that this review will be useful for further research on mitochondrial gene editing technologies to optimize the treatment of mitochondrial diseases in the future.展开更多
目的分析温州地区120例耳聋患者的致聋原因,并探讨线粒体DNA(mitochondrial DNA,mt DNA)12S r RNA基因A1555G和C1494T突变与耳聋之间的关系。方法对我院收集的120例耳聋患者进行分子流行病学的调查,并针对线粒体1555和1494位点进行引物...目的分析温州地区120例耳聋患者的致聋原因,并探讨线粒体DNA(mitochondrial DNA,mt DNA)12S r RNA基因A1555G和C1494T突变与耳聋之间的关系。方法对我院收集的120例耳聋患者进行分子流行病学的调查,并针对线粒体1555和1494位点进行引物设计,通过PCR扩增,产物Sanger测序后比对标准序列,检测A1555G和C1494T突变的频率以及和患者使用氨基糖苷类抗生素的相关性。结果在120例重度耳聋患者中具有氨基糖苷类抗生素用药史的有66例(55%),家族性遗传耳聋有22例(18.3%),近亲结婚可能致聋有10例(8.3%),不明原因的耳聋有22例(18.3%);我们还发现,有9例患者携带线粒体A1555G突变,突变的阳性率为7.5%,1例携带C1494T突变,阳性率为0.83%,这10例患者均有用药史。结论遗传因素和氨基糖苷类用药史是导致耳聋的重要原因,其中A1555G突变和C1494T突变是耳聋较为常见的线粒体DNA突变,这对早期诊断和预防药物性耳聋具有一定的临床意义。展开更多
基金supported by the National Key R&D Program of China(No.2022YFA1104300,2021YFA1101902)the National Natural Science Foundation of China(No.82170364,82003756)+4 种基金the Natural Science Foundation of Jiangsu Province,China(No.BK20200800)China Postdoctoral Science Foundation(No.2022M712312)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(No.21KJB310003)Jiangsu Funding Program for Excellent Postdoctoral Talent(China)(No.2022ZB577)Jiangsu Cardiovascular Medicine Innovation Center(China)(No.CXZX202210).
文摘Mitochondrial diseases are a heterogeneous group of inherited disorders character-ized by mitochondrial dysfunction,and these diseases are often severe or even fatal.Mito-chondrial diseases are often caused by mitochondrial DNA mutations.Currently,there is no curative treatment for patients with pathogenic mitochondrial DNA mutations.With the rapid development of traditional gene editing technologies,such as zinc finger nucleases and tran-scription activator-like effector nucleases methods,there has been a search for a mitochon-drial gene editing technology that can edit mutated mitochondrial DNA;however,there are still some problems hindering the application of these methods.The discovery of the DddA-derived cytosine base editor has provided hope for mitochondrial gene editing.In this paper,we will review the progress in the research on several mitochondrial gene editing technologies with the hope that this review will be useful for further research on mitochondrial gene editing technologies to optimize the treatment of mitochondrial diseases in the future.
文摘目的分析温州地区120例耳聋患者的致聋原因,并探讨线粒体DNA(mitochondrial DNA,mt DNA)12S r RNA基因A1555G和C1494T突变与耳聋之间的关系。方法对我院收集的120例耳聋患者进行分子流行病学的调查,并针对线粒体1555和1494位点进行引物设计,通过PCR扩增,产物Sanger测序后比对标准序列,检测A1555G和C1494T突变的频率以及和患者使用氨基糖苷类抗生素的相关性。结果在120例重度耳聋患者中具有氨基糖苷类抗生素用药史的有66例(55%),家族性遗传耳聋有22例(18.3%),近亲结婚可能致聋有10例(8.3%),不明原因的耳聋有22例(18.3%);我们还发现,有9例患者携带线粒体A1555G突变,突变的阳性率为7.5%,1例携带C1494T突变,阳性率为0.83%,这10例患者均有用药史。结论遗传因素和氨基糖苷类用药史是导致耳聋的重要原因,其中A1555G突变和C1494T突变是耳聋较为常见的线粒体DNA突变,这对早期诊断和预防药物性耳聋具有一定的临床意义。
