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在DDX17中单基de novo变异会导致神经发育障碍

Eleanor G Seaby^1,2, Annie Godwin³, Géraldine Meyer-Dilhet⁴

¹Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.

Brain : a journal of neurology

|October 15, 2024

概括

新的研究确定了DDX17基因是神经发育障碍的潜在原因. DDX17的变种影响神经元发育和基因表达,影响智力障碍和运动技能.

科学领域:

遗传学遗传学是一个
神经科学是一个神经科学.
分子生物学分子生物学

背景情况:

RNA螺旋酶DDX17与早期的神经元分化有关.
神经发育现象,包括智力障碍和运动延迟是常见的.
对于DDX17在神经发育障碍中的作用尚不清楚.

研究的目的:

在神经发育表型中研究DDX17中新一代单基变异的作用.
探索DDX17对哺乳动物和非哺乳动物模型中神经元发育的功能影响.
为了确定DDX17相关的神经发育缺陷背后的分子机制.

主要方法:

对11名DDX17变种患者的病例系列分析.
在子宫和外生皮质电解在小鼠中,以评估神经元迁移和轴突复杂性.
在Xenopus tropicalis中进行CRISPR/Cas9基因编辑,以创建马赛克脆口和异性淘汰.
对DDX17-Knockdown神经母细胞瘤细胞的转录组分析.

主要成果:

所有11名患者都呈现了神经发育现象型,主要是智力障碍,言语/语言延迟和运动延迟.
在小鼠中,DDX17的淘汰导致神经元迁移的延迟和皮质轴突复杂性的减少.
在DDX17敲击鼠标神经元和Xenopus幼中观察到减少的轴突外生长.
异种类型的Xenopus表现出神经发育缺陷和神经行为表型受损.
转录组分析揭示了DDX17敲击细胞中神经发育基因的差异表达.

结论:

在DDX17中De novo变异与神经发育障碍有关.
DDX17在哺乳动物和非哺乳动物的神经元发育中起着至关重要的作用,包括轴突生长和迁移.
DDX17影响了参与神经发育过程的关键基因的表达.

关键词:

这种RNA基酶是RNA基酶.鼠标模型鼠标模型鼠标模型神经发育/运动延迟神经元发育的神经元发育新型基因障碍新型基因障碍这是一个Xenopus模型.

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