非综合征型唇腭裂家系IFT172基因突变的功能分析

doi:10.13701/j.cnki.kqyxyj.2025.06.011

口腔医学研究 ›› 2025, Vol. 41 ›› Issue (6): 517-520.DOI: 10.13701/j.cnki.kqyxyj.2025.06.011

非综合征型唇腭裂家系IFT172基因突变的功能分析

罗雯迪, 曹海燕, 左伊宁, 何淼^*

口颌系统重建与再生全国重点实验室,口腔生物医学教育部重点实验室,口腔医学湖北省重点实验室,武汉大学口腔医(学)院湖北武汉 430079

收稿日期:2024-11-19 发布日期:2025-06-25
通讯作者: *何淼,男,E-mail: hemiao@whu.edu.cn
作者简介:罗雯迪(2000~ ),女,武汉人,硕士在读,研究方向:儿童口腔医学。
基金资助:
国家自然科学基金(编号:81970904)

Functional Analysis of IFT172 Mutations in Families with Non-syndromic Cleft Lip with or without Palate

LUO Wendi, CAO Haiyan, ZUO Yining, HE Miao^*

State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China

Received:2024-11-19 Published:2025-06-25

摘要/Abstract

摘要： 目的: 对两个非综合征型唇腭裂家系中筛查到的IFT172(intraflagellar transport 172)基因突变进行功能分析,进一步明确IFT172在唇腭裂中的致病机制。方法: 对前期工作中鉴定的IFT172突变进行保守性分析和蛋白质结构预测。构建野生型和突变体质粒,转染人胚胎腭板间充质细胞(human embryonic palatal mesenchyme,HEPM),进行转录组测序并对差异表达基因进行分析。结果: IFT172基因中的两个错义突变位点,c.4163A>G(p.Y1388C)和c.1507A>G(p.R503G),在物种间均高度保守,两个突变均导致蛋白质空间构象改变。转录组测序结果显示,差异表达基因富集于坏死性凋亡、调控细胞多能性等信号通路。结论: IFT172基因错义突变可能通过改变蛋白质构象,影响细胞凋亡和细胞多能性并参与唇腭裂的发生。

关键词: IFT172, 初级纤毛, 非综合征型唇腭裂, 转录组测序

Abstract: Objective: To further define the pathogenic mechanism of intraflagellar transport 172 (IFT172) in cleft lip and palate through functional analysis of IFT172 mutations identified in two families with non-syndromic cleft lip with or without palate. Methods: The IFT172 mutations identified in the previous work were subject to conservation analysis and protein structure prediction. Wild-type and mutant plasmids were constructed and transfected into human embryonic palatal mesenchyme (HEPM) cells. Transcriptome sequencing was performed and differentially expressed genes were analysed. Results: Two missense mutations in the IFT172, c.4163A>G (p.Y1388C) and c.1507A>G (p.R503G), were highly conservative among different species, and both mutations resulted in altered spatial conformation of the protein. The differentially expressed genes were enriched in pathways such as necroptosis and regulation of cell pluripotency. Conclusion: The missense mutations in the IFT172 may be involved in cleft lip and palate by altering protein conformation and affecting necroptosis and cell pluripotency.

Key words: IFT172, primary cilia, non-syndromic cleft lip with or without palate, transcriptome sequencing

罗雯迪, 曹海燕, 左伊宁, 何淼. 非综合征型唇腭裂家系IFT172基因突变的功能分析[J]. 口腔医学研究, 2025, 41(6): 517-520.

LUO Wendi, CAO Haiyan, ZUO Yining, HE Miao. Functional Analysis of IFT172 Mutations in Families with Non-syndromic Cleft Lip with or without Palate[J]. Journal of Oral Science Research, 2025, 41(6): 517-520.

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非综合征型唇腭裂家系IFT172基因突变的功能分析

Functional Analysis of IFT172 Mutations in Families with Non-syndromic Cleft Lip with or without Palate

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