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两种新型的AXIN2变体在孤立的牙生殖和AXIN2-关联的牙生殖模式
Chenxin Geng1, Bichen Lin2, Yang Liu1
1Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, No.22, Zhongguancun South Avenue Haidian District, Beijing, 100081, China.
BMC oral health
|December 8, 2025
概括
这项研究确定了两种与牙发生相关的新AXIN2基因变异,为它们的病原性提供了功能性证据. 这些发现有助于为患有孤立牙产生症的家庭进行遗传诊断.
科学领域:
- 遗传学 是一个遗传学.
- 发展生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- AXIN2基因的变异与结直肠癌和牙发育综合征有关.
- 此前,只有19种AXIN2变异与牙产生有关.
- 这项研究的重点是识别孤立牙产生中的新型AXIN2变异.
研究的目的:
- 在具有孤立牙发育的个体中识别新型AXIN2变异.
- 使用多种方法评估这些变异的致病性.
- 通过文献综述,总结AXIN2-关联牙发生的模式.
主要方法:
- 整体外基因组测序 (WES) 用于变种检测.
- 在PBMC中进行cDNA测序和mRNA表达分析.
- 生物信息分析,结构建模和体外功能测试用于病原性评估.
- 系统的文献综述用于模式特征.
主要成果:
- 发现了两种新型异质合体AXIN2变体:一个误解 (p.Thr693Met) 和一个拼接变体 (p.Arg354Leufs*2).
- 生物信息分析将分类变体归类为可能致病性/致病性.
- 功能测试证实了异常的Wnt/β-catenin信号激活 (p.Thr693Met) 和减少的AXIN2转录水平 (p.Arg354Leufs*2).
- 第二前 (下和大) 是最常缺失的牙.
结论:
- 扩大了与孤立牙产生相关的AXIN2变异的已知谱.
- 提供了 in vitro 功能性证据,支持已识别的变种的致病性.
- 为受影响家庭的遗传诊断和咨询提供了见解.
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