先天上颌尖牙缺失家系的致病基因的研究

›› 2020, Vol. 40 ›› Issue (6): 513-516.

先天上颌尖牙缺失家系的致病基因的研究

杨帆¹,姚思玥¹,于鑫¹,范力文²,潘永初³,王林⁴

1. 南京医科大学附属口腔医院
2. 南京医科大学
3. 南京医科大学口腔医学院
4. 南京医科大学附属江苏省口腔医院正畸科

收稿日期:2020-02-10 修回日期:2020-03-23 出版日期:2020-06-28 发布日期:2020-06-28
通讯作者: 潘永初 E-mail:panyongchu@njmu.edu.cn
基金资助:
国家自然科学基金

Identification of pathogenic genes in a canine agenesis family

Received:2020-02-10 Revised:2020-03-23 Online:2020-06-28 Published:2020-06-28

摘要/Abstract

摘要： 摘要目的：应用全基因组外显子测序技术探究先天上颌尖牙缺失的致病基因。方法：本研究对象为一个先天上颌尖牙缺失的核心家系，该家系由两个上颌尖牙缺失的患者和一个健康成员构成。对该家系成员进行血液样本采集及DNA提取。通过全基因组外显子测序技术及生物信息学分析筛选可能的致病基因。并通过Sanger测序的方法对筛选出的致病基因突变进行验证。并对验证后的基因进行功能预测及突变位点氨基酸保守性分析。结果：通过全基因组外显子测序发现此家系的两名上颌尖牙缺失的患者在ITGAV基因上存在c.C2381G的突变，而在该家系的健康成员中并未发现此突变。此突变为错义突变导致了脯氨酸变成了精氨酸。Sanger测序也证实该基因的突变在此家系中符合疾病共分离。生物信息学分析显示ITGAV 在小鼠牙胚和人的牙胚中均有表达。且突变位置的脯氨酸在各物种间具有高度保守性。结论：研究结果提示ITGAV可能是导致该上颌尖牙缺失家系的致病基因。

关键词: 上颌尖牙缺失, 全基因组外显子测序, 基因突变

Abstract: Abstract： Objective: The aim of our study is to explore the pathogenic genes or susceptibility genes for maxillary canine agenesis by whole exome sequencing (WES). Method: The study was performed on a Chinese tooth agenesis family which consisted of two maxillary canine agenesis patients and a healthy person. Collecting the peripheral blood of the families and genomic DNA was extracted. Then Whole exome sequencing was performed on the family. Likely pathogenic variants were filtered out by bioinformatic analysis. Then PCR-Sanger sequencing was performed in all of the family members for verification of the candidate variants. The functional of the candidate gene and the conservation of the mutated amino acid were predicted by bioinformatic analysis. Result: ITGAV (c.C2381G) was filtered out in the two maxillary canine agenesis patients but not in the healthy person. This missense mutation made Proline (Pro) change to Arginine (Arg). Then Sanger sequencing identified that the mutation was coseparation in this family. Bioinformatic analysis showed that the ITGAV expressed in the mouse and human tooth germ. Besides that the Proline in mutated site was highly conserved in different species. Conclusion: The study showed that ITGAV may be the pathogenic gene for maxillary canine agenesis.

Key words: Maxillary canine agenesis, whole exome sequencing, gene mutation

中图分类号:

R597

杨帆姚思玥于鑫范力文潘永初王林. 先天上颌尖牙缺失家系的致病基因的研究[J]. 口腔医学, 2020, 40(6): 513-516.

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