PITX2突变导致非综合征型先天缺牙的遗传研究  

Genetic Study of PITX2 Mutation Leading to Non-syndromic Tooth Agenesis.

作　　者：张亲 林师仪 张婷婷[2] 王慧娟 叶杨杨 张向宇[1] ZHANG Qin;LIN Shiyi;ZHANG Tingting;WANG Huijuan;YE Yangyang;ZHANG Xiangyu(Department of Pediatric Dentistry, Stomatological Hospital of Tianjin Medical University, Tianjin 300070, China;Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Tianjin Medical University, Tianjin 300070, China.)

机构地区：[1]天津医科大学口腔医院儿童口腔科,天津300070 [2]天津医科大学口腔医院口腔颌面外科,天津300070

出　　处：《口腔医学研究》2022年第7期628-631,共4页Journal of Oral Science Research

基　　金：天津市卫生健康委员会重点攻关项目(编号:15KG139)。

摘　　要：目的:研究1例非综合征型先天缺牙(non-syndromic tooth agenesis,NSTA)患者家系的遗传学病因。方法:采集先证者及家庭成员的外周血,利用全外显子组测序技术和生物信息学工具进行变异检测及分析。锁定先证者候选基因后,通过Sanger测序技术验证变异位点。运用Protean、I-TASSER软件分别分析突变蛋白的二级结构和三维(3D)模型,并与野生型进行比较分析。结果:先证者及母亲均携带同一PITX2新发杂合移码突变(c.176delT,p.I59fsX149)。该突变改变同源结构域和OAR结构域,影响DNA结合活性及对下游基因的激活诱导能力。二级结构预测显示突变蛋白α螺旋数量减少,3D模型空间构象变化显著。结论:PITX2移码突变(c.176delT)可能是先证者患有NSTA的病因之一。本研究扩展了PITX2基因突变谱,为进一步探讨PITX2与NSTA之间的相关性提供临床与遗传学证据。Objective:To study the genetic etiology of a patient with non-syndromic tooth agenesis(NSTA)in a family.Methods:Peripheral blood of the proband and family numbers was collected,and whole-exome sequencing technique and bioinformatics tools were used to detect and analyze variants separately.After identifying the candidate gene of the proband,the variant site was verified by Sanger sequencing.The secondary structure and three-dimensional(3D)model of the mutant protein were analyzed and compared with the wild type using Protean and I-TASSER software.Results:Both the proband and his mother carried the same novel heterozygous frameshift mutation(c.176delT,p.I59fsX149)in PITX2.This mutation altered homeodomain and OAR domain,which affected the activity of DNA binding and the ability to activate downstream genes.The prediction of secondary structure revealed a decrease in the number ofαhelices of the mutant protein,and 3D model showed significant spatial conformational changes.Conclusions:The PITX2 frameshift mutation(c.176delT)may be one of the causes of NSTA in the proband.Our study extends the mutation spectrum of PITX2,and provides clinical and genetic evidence for further exploration of the association between PITX2 and NSTA.

关 键 词：先天缺牙 PITX2 全外显子组测序 

分 类 号：R783.3[医药卫生—口腔医学]