在患有神经线粒体疾病的中国儿童中发现新的致病性mtDNA变异
Zhimei Liu1, Kexin Pan2, Mingzhao Wang1
1Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Annals of clinical and translational neurology
|February 6, 2025
概括
研究人员在患有神经线粒体疾病的中国儿童中发现了五种新型致病性线粒体DNA (mtDNA) 变异. 功能性研究证实这些变体会损害线粒体功能,进步我们对这些条件的理解.
科学领域:
- 遗传学 遗传学 是一个
- 线粒体生物学 线粒体生物学
- 儿科神经学 儿科神经学
背景情况:
- 线粒体基因组变异与儿科神经系统疾病有关.
- 中国儿童的线粒体DNA (mtDNA) 突变谱尚未完全理解.
研究的目的:
- 在中国儿童中具有线粒体疾病的病原性mtDNA变异的全面表征.
- 在临床,分子和功能层面分析变异.
主要方法:
- 分析了600多名疑似患有线粒体疾病的中国儿童.
- 整体外基因组测序 (WES) 和全mtDNA测序.
- 在体中,功能性 (纤维细胞/混合细胞) 和转录组概况分析.
主要成果:
- 在227名儿童中确定了54种致病性/可能致病性mtDNA变异.
- 检测到八种新型异质体变异;五个功能性验证为致病性.
- 五种新型变异 (m.4275G>A,m.10407G>A,m.5828G>A,m.3457G>A,m.13112T>C) 影响了线粒体呼吸和ATP生成.
- 一种变体 (m.8427T>C) 被确定为一种罕见的多态变体.
结论:
- 在患有线粒体疾病的中国儿童中重新检查并扩大了mtDNA突变谱.
- 确定了五种新的致病性mtDNA变异,其功能与神经线粒体疾病有关.
- 提供了关键的分子和功能数据,用于诊断和理解这些条件在中国儿科人口.
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