重度先天缺牙患者WNT10A基因新突变位点的检测及其种植修复  

Novel mutations identified in the WNT10A gene and implant rehabilitation of patients with severe tooth agenesis

作　　者：蒋欣珂 喻康 周梦琪[2] 吴轶群[2] 王凤[1] JIANG Xinke;YU Kang;ZHOU Mengqi;WU Yiqun;WANG Feng(Department of Oral Implantology,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine&College of Stomatology,Shanghai Jiao Tong University&National Center for Stomatology&National Clinical Research Center for Oral Diseases&Shanghai Key Laboratory of Stomatology,Shanghai 200011,China;Department of Second Dental Center,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine&College of Stomatology,Shanghai Jiao Tong University&National Center for Stomatology&National Clinical Research Center for Oral Diseases&Shanghai Key Laboratory of Stomatology,Shanghai 201999,China)

机构地区：[1]上海交通大学医学院附属第九人民医院口腔种植科,上海交通大学口腔医学院,国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海200011 [2]上海交通大学医学院附属第九人民医院第二门诊部,上海交通大学口腔医学院,国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海201999

出　　处：《口腔疾病防治》2022年第10期724-732,共9页Journal of Prevention and Treatment for Stomatological Diseases

基　　金：上海市科学技术委员会科技计划项目(21ZR1437700);中国医学科学院与健康科技创新工程项目资助(2019-12M-5-037);上海交通大学医学院附属第九人民医院生物样本库项目(YBKB202101)。

摘　　要：目的 探讨WNT10A基因突变重度先天缺牙(恒牙先天缺失数目≥6)患者的临床表型及其相关种植修复治疗预后情况。方法 对在临床收集到的先天缺牙患者进行口内检查、遗传病史采集和全外显子测序,筛查并纳入WNT10A基因出现突变的患者。对先证者及其家系成员进行Sanger测序后与正常人群的WNT10A基因序列进行比对。利用基因突变功能预测、基因保守性分析和蛋白结构预测分析来评估患者WNT10A基因突变的致病性,并对缺牙患者进行相关种植修复治疗。结果 在6例无血缘关系的重度先天缺牙患者中共检测到5个WNT10A基因突变,其中c.26G>A(p.Trp9X)和c.1036delT(p.Cys346fs)为新检出突变。突变功能预测的结果显示这些突变表现出一定程度的致病性。患者平均缺牙数目为(15.33±8.64)颗,其中上颌尖牙缺失率最高(100%),下颌第一磨牙缺失率最低(25%)。对患者采取种植修复,种植体获得了良好的骨结合,患者口腔功能得到了恢复。结论 本研究丰富了重度先天缺牙患者的WNT10A基因突变谱,为遗传诊断和产前咨询提供了新的证据。同时,种植修复可有效恢复这类患者缺牙及口颌功能。Objective To detect WNT10 A gene mutations in patients with oligodontia or anodontia(≥6 teeth missing)and analyze their dental phenotype.Methods Patients with oligodontia or anodontia were enrolled from the clinic for oral examination,genetic history collection and whole exon sequencing,and patients with WNT10 A gene mutations were included.Sanger sequencing was utilized to validate the WNT10 A gene variations in probands and family members compared with the normal sequence.The pathogenicity of WNT10 A mutations was evaluated by functional prediction,conservation analysis and structure prediction of protein mutants.Implant rehabilitation was applied to restore the patients’oral function.Results Five WNT10 A gene mutations were detected in six unrelated patients,and c.26 G>A(p.Trp9 X)and c.1036 del T(p.Cys346 fs)were novel mutations with pathogenic potential.The mean number of missing teeth was(15.33±8.64)per case.The most frequently missing permanent teeth were maxillary canines(100%),and the least frequently missing teeth were mandibular first molars(25%).Implant rehabilitation was applied in five patients,and patients were found to have ideal implant osseointegration and functional restoration.Conclusion This study identified novel WNT10 A gene pathogenic variants,enriching the WNT10 A gene spectrum and providing new evidence for genetic diagnosis and prenatal consultation.Implant rehabilitation was also proven to be a treatment option for these patients.

关 键 词：先天缺牙 全口无牙症 外胚层发育不良 WNT10A基因 基因突变 Sanger测序 种植修复 颧种植 

分 类 号：R78[医药卫生—口腔医学]