先天性镜像运动与RAD51的缺陷聚合有关
Oriane Trouillard1,2, Pauline Dupaigne3, Margaux Dunoyer4
1INSERM, CNRS, Institut de Biologie Paris Seine, IBPS, Neuroscience Paris Seine, NPS, Sorbonne Université, F-75005 Paris, France.
Journal of medical genetics
|June 12, 2023
概括
先天性镜像运动 (CMM) 是由RAD51平分素不足引起的,其中减少的RAD51蛋白质会影响皮质脊髓管的发育. 这项研究证实了RAD51的存在.
科学领域:
- 遗传学和神经科学 遗传学和神经科学
- DNA 修复机制的修复机制
- 人类发育障碍 人类发育障碍
背景情况:
- 先天性镜像运动 (CMM) 是与皮质脊柱管异常发育相关的非自愿运动.
- CMM是一种罕见的自体主导性疾病.
- 以前假设RAD51,对于DNA修复至关重要,参与CMM.
研究的目的:
- 在CMM家族中识别RAD51基因中的新致病变异.
- 为了研究RAD51变体的功能后果.
- 阐明RAD51在CMM病变发生过程中的作用.
主要方法:
- 在五个CMM家族中对RAD51的桑格测序.
- 在患者的淋巴细胞中分析RAD51mRNA和蛋白质表达.
- 生物化学描述RAD51变体的功能.
主要成果:
- 患有CMM的患者表现出较低水平的RAD51蛋白.
- 无症状携带者表现出较少明显的RAD51减少.
- 突变RAD51蛋白在聚合,DNA结合和链交换中表现出功能丧失.
结论:
- 包括功能丧失变体在内的RAD51哈普洛缺陷导致CMM.
- 转录后补偿可能解释不完全的透性.
- 改变RAD51功能会影响皮质脊髓轴突在发育过程中的指导,为神经发育提供新的见解.
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