在ASCL5的一个错误变异导致了lobodontia
Thanakorn Theerapanon1,2, Narin Intarak2, Khanti Rattanapornsompong2
1Interdisciplinary Program of Biomedical Sciences, Graduate School, Chulalongkorn University, Bangkok, Thailand.
Nature communications
|February 11, 2026
概括
这项研究确定ASCL5基因变异 (p.Glu92Lys) 是导致牙突变的原因,这是一个罕见的牙异常. 在小鼠中的功能性研究证实了ASCL5的存在.
科学领域:
- 遗传学 遗传学是一种遗传学.
- 发展生物学 发展生物学
- 口腔病理学 口腔病理学
背景情况:
- 牙牙 (Lobodontia) 是一种罕见的牙异常,其特点是额外的牙尖和单一的金字塔形状的牙根.
- 以前的研究表明与CACNA1S基因变异存在联系,但证据不确定.
研究的目的:
- 为了确定龙牙的遗传基础.
- 研究ASCL5在面发育中的作用.
主要方法:
- 在受影响的家庭中进行了微卫星基因型和全基因组测序.
- 用CRISPR/Cas9技术创建Ascl5突变小鼠用于功能研究.
- 进行了转录基因分析和光酶试验,以评估基因功能.
主要成果:
- 所有17名龙牙患者都携带ASCL5 c.274G>A (p.Glu92Lys) 变异,在未受影响的个体中不存在.
- Ascl5突变小鼠表现出牙异常和面缺陷,证实了ASCL5的重要作用.
- 这种p.Glu92Lys变种影响了DLX2激活,表明了病原性.
结论:
- ASCL5是lobodontia的致病基因,修订了其已知的遗传病因学.
- ASCL5在哺乳动物的面图案和牙发育中发挥着关键作用.
- 鉴定到的ASCL5变异为这种罕见的牙异常提供了分子解释.
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