扩大NDUFAF3相关的线粒体疾病的表型和生化谱
Amelie T van der Ven1, Alfredo Cabrera-Orefice2, Isabell Wente2
1Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Molecular genetics and metabolism
|August 12, 2023
概括
递归的NDUFAF3变体会导致线粒体疾病. 这项研究详细介绍了一名患有异常症状的10岁患者,扩大了已知的NDUFAF3疾病谱,并澄清了它在复杂I组装中的作用.
科学领域:
- 生物化学 生物化学
- 遗传学 遗传学 是一个
- 线粒体生物学 线粒体生物学
背景情况:
- 衰退性NDUFAF3变体与严重的复杂I (CI) 相关的线粒体疾病 (MDs) 有关.
- 之前报告的患者通常出现严重的神经症状和婴儿期致命结果.
- 这项研究研究了一名患有非典型的,晚期发作的病例的患者.
研究的目的:
- 描述一个患有NDUFAF3变异的10岁患者的基因型,表型和生物化学方面.
- 扩大对NDUFAF3相关MD的表型谱的理解.
- 进一步阐明NDUFAF3在复杂I生物发生和组装中的作用.
主要方法:
- 三外体序列测定用于识别遗传变异.
- 线粒体复合体I活动的光谱分析分析.
- 对患者衍生的纤维细胞进行复杂的分析,以评估复杂I组件和中间复杂物.
主要成果:
- 一名10岁的患者出现了神经发育障碍,运动不耐受, dystonia 和基底腺异常.
- 在NDUFAF3中确定了复合异构性致病变体.
- 纤维细胞分析显示复合I活性降低,NDUFAF3和复合I水平严重降低,以及早期CI组装中间体的积累,包括具有组装因子的自由单体CI.
结论:
- 患者的非典型表现扩大了NDUFAF3相关线粒体疾病的已知的表型谱.
- 复合体分析证实了NDUFAF3在CI生物发生中的作用,并为CI成熟和超复合体形成提供了新的见解.
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