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双性NDUFA9变体会导致一种进展性神经发育障碍,显着的 dystonia 和线粒体复合体 I 缺陷

Francesca Magrinelli¹, Lucie S Taylor^2,3, Sahar Sedighzadeh^4,5

¹Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, United Kingdom.

Brain communications

|October 10, 2025

概括

在NDUFA9基因中的双变异会导致进展性神经发育障碍. 这种线粒体复合体I缺陷通常表现为 dystonia,神经衰退,以及特定的 MRI 发现,扩大已知的疾病谱.

科学领域:

生物化学生化学
遗传学遗传学是一个
神经学神经学

背景情况:

双性NDUFA9变异很少见,对相关疾病的临床和遗传特征的理解有限.
之前的报道仅在四个人中记录了NDUFA9变异,需要进一步调查.

研究的目的:

划分NDUFA9相关疾病的表型和基因型谱.
扩大受影响个体的队列,并描述疾病的进展和临床表现.

主要方法:

选了全球遗传数据库,用于双基NDUFA9变体的个体.
收集和分析表型数据,包括临床特征,神经成像和遗传信息.
执行功能性调查,包括蛋白质建模和纤维细胞分析,为选定的情况下.

主要成果:

鉴定出12个 (8个新增,4个报告) 具有双性NDUFA9变异的个体.
常见的特征包括神经发育迟缓,运动恶化, dystonia,,和金字塔标志.
所有患者都表现出基底腺MRI异常;90%的患者表现出神经发育障碍,如果存活超过4个月.
确定了五种新的NDUFA9变种,Arg360被认为是突变热点.
功能性研究表明NDUFA9错误折叠,干扰接口,并损害了复合体I组装/活动.

结论:

双性NDUFA9变体会导致一种渐进的线粒体复合物I缺乏障碍.
这种疾病呈现出广泛的神经发育问题,突出的 dystonia 和特征性的 Leigh 综合征 MRI 模式.
这项研究显著扩大了NDUFA9相关疾病的已知临床遗传特征.

关键词:

李氏综合征 (Leigh综合征) 是一种乳酸性酸性消化症乳酸性酸性消化症突变热点是一个突变热点.发作发作这些性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性,性等.

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