误解变体削弱SOX9的降基因,与牙生殖缺陷,脊椎病和其他骨特征有关
Imane Ettaki1, Abdul Haseeb2, Anirudha Karvande2
1Virology Unit, Immunovirology Laboratory, Institut Pasteur du Maroc, Casablanca 20360, Morocco; Laboratory of Cellular and Molecular Pathology, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, Casablanca 20000, Morocco.
HGG advances
|January 11, 2025
概括
新的SOX9基因变异导致牙喷发延迟和骨问题. 这些功能获取突变破坏了SOX9蛋白的功能,影响了牙的发育,并可能导致脊椎病变.
科学领域:
- 遗传学 遗传学 是一个
- 发展生物学 发展生物学
- 人体生理学 人体生理学
背景情况:
- SOX9是一种转录因子,对体生成和性别决定至关重要.
- SOX9变种与骨疾病和性发育问题有关,但它们在牙发育中的作用尚不清楚.
- 牙喷发延迟是一种临床观察,可以表明潜在的遗传或发育异常.
研究的目的:
- 在没有已知的综合征的儿童中调查牙喷发延迟的遗传基础.
- 识别新型SOX9变异并阐明它们对牙发育和骨发生的功能影响.
- 探索SOX9光降解基因 (CPD) 在蛋白质稳定性和交换活化功能的作用.
主要方法:
- 在9名患有不明原因的牙喷发延迟的儿童身上进行了全外测序.
- 在培养细胞中进行了功能测定,以评估已识别的SOX9变异对蛋白质降解和交换活化的影响.
- 使用结构建模来预测变体对SOX9/FBXW7相互作用的影响.
主要成果:
- 在儿童中发现了两种新的SOX9变体 (p.Thr239Pro和p.Thr239Pro/p.Thr240Pro),这些变体是主要牙喷发延迟的.
- 确定的变种,特别是影响p.Thr240的变种,影响了FBXW7介导的SOX9降解.
- 所有已识别的变异都增加了SOX9记者基因的激活,这表明了功能获取机制.
- 一名患者表现出严重的脊椎病变和面异常,将SOX9变异与更广泛的骨缺陷联系起来.
结论:
- SOX9在牙发育中发挥着关键作用,功能增益变异可能导致牙喷发延迟.
- 这种SOX9的氧降解控制 (CPD) 模式对于调节SOX9的稳定性和功能至关重要.
- 除了牙缺陷外,SOX9变种还可以导致显著的骨异常,包括脊椎病.
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