缺少ZSCAN10会导致神经发育障碍,具有特征的耳面形
Lucia Laugwitz1,2, Fubo Cheng1, Stephan C Collins3
1Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tübingen, 72076, Germany.
Brain : a journal of neurology
|February 22, 2024
概括
由ZSCAN10基因变异引起的新遗传疾病导致神经发育延迟,面部不对称和耳部形. 这一发现有助于诊断以前无法解释的神经发育状况.
科学领域:
- 遗传学 是一个遗传学.
- 发展生物学 发展生物学
- 医学研究 医学研究
背景情况:
- 神经发育障碍 (NDD) 是遗传转诊的一个重要原因,已确定超过1500个位点,但许多患者缺乏遗传诊断.
- 转录因子功能障碍与综合征性NDD有关,突出显示了新基因发现和表型划分的必要性.
- 机器学习和先进的测序技术为识别新的疾病基因和理解复杂的表型提供了潜力.
研究的目的:
- 确定来自五个家庭的七个人神经发育迟缓和异形特征的遗传原因.
- 在细胞和动物模型中研究ZSCAN10功能丧失变体的功能后果.
- 描述与ZSCAN10缺乏相关的临床表型.
主要方法:
- 下一代测序被用来识别受影响个体的遗传变异.
- 功能性研究涉及ZSCAN10淘汰和变异模型在小鼠胚胎干细胞 (mESCs) 中使用基因表达,西部斑,ChIP-qPCR和免疫光.
- 现型特征包括神经成像,2D肖像分析 (GestaltMatcher) 和Zscan10淘汰赛小鼠胚胎的分析.
主要成果:
- 在ZSCAN10中,双基功能丧失变异被确定为七个个体中新型综合征NDD的原因.
- 在mESCs中ZSCAN10缺陷调节失调的基因与干细胞多能性和受损的DNA增强剂结合有关.
- 一致的临床特征包括全球发育迟缓,面部不对称,外耳和内耳形以及半圆通道发育不良.
结论:
- 在ZSCAN10中双基功能丧失的变体会导致一种新的综合征神经发育障碍.
- ZSCAN10在神经发育中起着至关重要的作用,其功能障碍导致特定的综合征特征.
- 这一发现扩大了NDD的遗传景观,并为受影响的家庭提供了分子诊断.
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