破坏性CHD8突变定义了发展早期自闭症的一个亚型
Raphael Bernier1, Christelle Golzio2, Bo Xiong3
1Department of Psychiatry, University of Washington, Seattle, WA 98195, USA.
Cell
|July 8, 2014
概括
在患有自闭症谱系障碍 (ASD) 的儿童中,对CHD8基因的基因分析确定了特定的突变. 这些突变与独特的ASD亚型有关,其特征是巨头症和胃肠道问题.
科学领域:
- 遗传学 是一个遗传学.
- 神经发育障碍 神经发育障碍
- 发展生物学 发展生物学
背景情况:
- 自闭症谱系障碍 (ASD) 是一种复杂的神经发育状况,具有显著的异质性.
- 在ASD中识别亚型的行为方法取得了有限的成功.
- 遗传因素越来越被认为是理解ASD病因的关键.
研究的目的:
- 调查CHD8基因在识别ASD遗传特异性亚型中的作用.
- 描述与发展延迟或ASD个体中CHD8突变相关的表型特征.
主要方法:
- 在3730名患有发育迟缓或ASD的儿童队列中,重新测序了ASD相关基因CHD8.
- 突变分析将受影响的个体与一个由8,792个个体组成的对照组进行比较,包括未受影响的兄弟姐妹.
- 发现CHD8突变的个体的表型特征.
- 使用斑马鱼模型来回顾人类表型的功能研究.
主要成果:
- 在研究队列中发现了CHD8基因中的15个独立突变.
- 在对照组中没有发现切断CHD8突变,这表明存在强烈的关联.
- 具有CHD8突变的个体显示出 ASD 诊断的可能性很高,并且对大脑症,明显的面部特征和胃肠道投诉进行了丰富.
- 斑马鱼模型的CHD8中断表现出头部的大小和胃肠道运动能力受损,反映了人类的症状.
结论:
- 在CHD8基因中的干扰定义了自闭症谱系障碍的特定亚型.
- CHD8突变突出了大脑发育和肠道神经系统功能之间的联系.
- 这项研究为独特的ASD亚型提供了遗传基础,并揭示了新的并发症.
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