在CCDC91中发生的一种突变,Homo sapiens卷轴-卷轴域含有91蛋白质,导致自体主导的acrokeratoelastoidosis
Yunlu Zhu1,2, Yun Bai1, Wannian Yan1
1Shanghai Skin Disease Hospital, School of Medicine, Tongji Medical University, Shanghai, China.
European journal of human genetics : EJHG
|April 16, 2024
概括
研究人员确定了CCDC91基因中的剪接突变是导致罕见的遗传性皮肤疾病Acrokeratoelastoidosis (AKE) 的原因. 这一发现揭示了CCDC91
科学领域:
- 遗传学 是一个遗传学.
- 皮肤病学 皮肤病学
- 分子生物学分子生物学
背景情况:
- 阿克罗卡托埃拉斯托伊多症 (AKE) 是一种罕见的自体主导性遗传性皮肤疾病.
- 它的特点是四肢上的状斑块,其致病基因以前是未知的.
研究的目的:
- 确定AKE的致病基因.
- 阐明疾病进展背后的生物机制.
主要方法:
- 一个中国家庭的全基因组链接分析和全外因组测序.
- 在细胞模型中进行了shRNA淘汰和CRISPR/Cas9基因编辑.
- 免疫抑制以评估蛋白质的局部化和功能.
主要成果:
- 在CCDC91基因中发现了一个拼接突变 (1101+1G>A) 是AKE的原因.
- 这种突变导致异构体11跳转和CCDC91蛋白质中59个氨基酸的损失.
- 功能性研究表明弹性质运输受损,托波拉斯在戈尔吉和异常细胞外聚合物中积累.
结论:
- CCDC91基因对于适当的弹性质运输至关重要.
- 这一发现扩大了对AKE病原和CCDC91蛋白功能的理解.
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