具有线粒体复合体I组合基因NDUFAF5突变的患者的表型异质性
Pin-Shiuan Chen1, Ni-Chung Lee2,3, Chieh-Ju Sung4
1Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
Movement disorders : official journal of the Movement Disorder Society
|September 27, 2023
概括
在NDUFAF5突变导致利氏综合征,与一个常见的变体 (p.Met279Arg) 显示不同的发病和结果. 这种变种在中国人口中普遍存在,并影响疾病的严重程度和预后.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 线粒体生物学 线粒体生物学
- 神经学 神经学
背景情况:
- 罕见的NADH:乌比金氧降解酶复合组合因子5 (NDUFAF5) 突变与李氏综合征有关.
- 李氏综合征是一种严重的早期发病的神经退行性疾病,影响线粒体能量生产.
研究的目的:
- 描述NDUFAF5突变的临床谱和功能后果.
- 调查NDUFAF5突变患者的遗传和表型变异性.
主要方法:
- 多中心招募双性NDUFAF5突变患者.
- 综合数据收集,包括临床,实验室和放射学发现.
- 使用患者衍生皮肤纤维细胞的线粒体功能测试.
主要成果:
- 来自七个家庭的9名患者被确定,其中c.836T>G (p.Met279Arg) 变种的患病率很高,特别是在中国血统的人群中.
- 观察到两种发病年龄,早期发病 (<3岁) 呈现严重的精神运动延迟和呼吸衰竭,晚期发病 (≥5岁) 呈现渐进性 dystonia.
- p.Met279Arg变体与表型异质性有关,晚发症患者表现出更好的预后和保存的门诊功能,可能受到修饰基因和线粒体功能的影响.
结论:
- 在NDUFAF5中的p.Met279Arg变体是研究人口中利氏综合征的重要原因,显示出相当大的表型多样性.
- 发病时的年龄是NDUFAF5相关的李氏综合征临床表现和预后的关键决定因素.
- 对遗传修饰剂和线粒体功能障碍的进一步研究是有必要的,以了解不同的结果.
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