全外显子测序检测非综合征型多数牙先天缺失家系中EDAR基因新突变的研究  

A novel EDAR mutation identified in nonsyndromic oligodontia patients by whole exome sequencing

作　　者：张红玉 杨丽媛 孟令强[1] 郑书深 马文盛[3] 杨冬茹[4] 沈文静[1] 侯彦[3] 刘晔[3] 任嘉宝 ZHANG Hongyu;YANG Liyuan;MENG Lingqiang;ZHENG Shushen;MA Wensheng;YANG Dongru;SHEN Wenjing;HOU Yan;LIU Ye;REN Jiabao(Department of Prosthodontics,Hebei Key Laboratory of Stomatology,Hebei Clinical Research Center for Oral Diseases,School and Hospital of Stomatology,Hebei Medical University,,Shijiazhuang050017,China;Xingtai Medical College;Department of Orthodontics,Hebei Clinical Research Center for Oral Diseases,School and Hospital of Stomatology,Hebei Medical University,Shijiazhuang;Department of Periodontics,Hebei Key Laboratory of Stomatology,Hebei Clinical Research Center for Oral Diseases,School and Hospital of Stomatology,Hebei Medical University,Shijiazhuang)

机构地区：[1]河北医科大学口腔医学院·口腔医院,口腔修复科,河北省口腔医学重点实验室,河北省口腔疾病临床医学研究中心,石家庄050017 [2]邢台医学院 [3]河北医科大学口腔医学院·口腔医院,口腔正畸科 [4]河北医科大学口腔医学院·口腔医院,牙周一科

出　　处：《实用口腔医学杂志》2021年第6期783-789,共7页Journal of Practical Stomatology

基　　金：河北省科技厅支撑计划(编号:17277734D);河北省科技厅民生科技专项(编号:203777108D);河北省科技厅卫生健康创新专项(编号:21377716D);河北省政府资助临床医学优秀人才培养项目补助计划(编号:2019061441-2);大学生创新性实验计划项目(编号:USIP2018057)。

摘　　要：目的:探索非综合征型多数牙先天缺失家系中新的致病突变,并为其致病机制的研究提供遗传学基础。方法:针对收集到的21个非综合征型多数牙先天缺失家系,提取家系核心成员外周血基因组DNA,对先证者DNA进行全外显子测序(WES)及Sanger测序验证。通过耐受性分析(SIFT)、多态性表现型分析(PolyPhen-2)、突变筛选分析(Mutation Taster)以及突变位点的保守性分析,筛选致病突变,重建比对突变EDAR蛋白与野生型EDAR蛋白三维结构的改变。结果:在21个非综合征型先天缺牙患者中发现一个新的EDAR基因错义突变c.338G>A(p.Cys113Tyr)以及一个已知的EDAR基因突变c.1138A>G(p.Ser380Arg)。结论:在非综合征型多数牙先天缺失患者中发现一个新的EDAR突变c.338G>A(p.Cys113Tyr),扩大了EDAR基因的突变谱。Objective:To investigate novel non-syndromic oligodontia(NSO)-associated variants and to provide genetic basis for the study of its pathogenesis.Methods:Peripheral blood samples were collected from the family members of 21 individuals with NSO for DNA extraction.Whole exome sequencing(WES)and Sanger sequencing were then performed for 21 probands.Subsequently,several bioinformatics database and 3D structure reconstruction of the altered protein for the variant were used for pathogenic mutation screening.Results:A novel missense mutation c.338G>A(Cys113Tyr)and a reported mutation c.1138A>G(p.Ser380Arg)in the EDAR gene were identified in 2 pedigrees of 21 patients.Conclusion:A novel EDAR missense mutation c.338G>A(Cys113Tyr)was identified in a family with NSO,the mutation spectrum of the EDAR gene is extended.

关 键 词：非综合征型先天缺牙 EDAR 突变 全外显子测序 

分 类 号：R781.9[医药卫生—口腔医学]