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双性FOXRED1突变会导致婴儿线粒体脑病变,并导致I复合体解体和基底腺变性

Cunhui Pan¹, Ruowei Zhu², Xi Huang¹

¹Department of Pediatrics, Clinical Research Center of Children's Neurodevelopmental Disabilities of Hunan Province, Xiangya Hospital, Central South University, Changsha 410008, China.

|December 18, 2025

概括

在FOXRED1基因中的双基因突变导致线粒体功能障碍,导致严重的神经系统疾病,如发育性和性脑病变 (DEE). 尼亚补充剂通过恢复NAD+/NADH平衡和降低乳酸盐水平,显示出潜在的治疗益处.

科学领域:

神经科学是一个神经科学.
线粒体生物学线粒体生物学
遗传学是一个遗传学.

背景情况:

发育性和性脑病变 (DEE) 是一种严重的神经疾病.
核编码的线粒体伴侣基因FOXRED1中的双基因突变与线粒体功能障碍有关,但以前与DEE无关.
福克斯RED1是线粒体复合体I的关键组装因子.

研究的目的:

调查双基FOXRED1突变在DEE病变发生中的作用.
分析FOXRED1突变对DEE患者线粒体功能的影响.
探索FOXRED1相关DEE的潜在治疗策略.

主要方法:

收集了两名DEE患者的临床数据和外周血液单核细胞 (PBMC),这些患者具有复合异性FOXRED1突变和对照.
进行了全面的线粒体表型鉴定:复杂I活性,呼吸应力测试,膜潜力,活性氧物种 (ROS) 水平和NAD+/NADH比率.
使用了体外 niacin 治疗,并评估了临床补充剂对血液乳酸盐水平的影响.

主要成果:

患者呈现出早期发作的耐药性发作,基底性关节病变,高乳糖血和发育回归.
福克斯RED1突变导致复合I活动和复合I分解减少了50%.
在患者中观察到线粒体去极化,氧化应激增加,以及不平衡的NAD+/NADH比率.
尼亚在体外恢复了NAD+/NADH比率,临床补充剂降低了血液中的乳酸盐水平.

结论:

双性FOXRED1突变与DEE的发病有关,导致显著的线粒体功能障碍.
这些患者的线粒体功能障碍包括I复合体活动受损,氧化应激和改变的NAD+/NADH平衡.
尼亚显示出作为治疗选择的潜力,用于管理FOXRED1相关DEE的代谢障碍.

关键词:

发育性和性脑病变,发育性和性脑病变.福克斯红色1 在线观看线粒体功能障碍线粒体功能障碍尼阿酸尼阿酸是最重要的.奥塔哈拉综合症 (Oohtahara Syndrome) 是一种

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