一个常染色体显性钙化不全型釉质发育不全家系的致病基因研究及多学科治疗  

Genetic analysis and multidisciplinary treatment of a pedigree affected with autosomal dominant hypocalcified amelogenesis imperfecta

作　　者：崔梦娟 柴利 翟蔷岚 汪政良 许彤 陈洁仪 刘超[1] CUI Meng-juan;CHAI Li;ZHAI Qiang-lan;WANG Zheng-liang;XU Tong;CHEN Jie-yi;LIU Chao(Department of Orthodontics,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,College of Stomatology,Shanghai Jiao Tong University,ational Center for Stomatology,National Clinical Research Center for Oral Diseases,Shanghai Key Laboratory of Stomatology,Shanghai Research Institute of Stomatology,Shanghai 200011;Department of Stomatology,Hospital of JIER Machine-Tool Group Co.,Ltd..Jinan 250000,Shandong Province;Department of Otorhinolaryngology,Shandong Provincial ENT Hospital.Jinan 250000,Shandong Province;Center for Molecular Medicine,Pediatrics Research Institute,Children's Hospital of Fudan University,Shanghai 201102,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正畸科,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,上海市口腔医学研究所,上海200011 [2]济南二机床集团有限公司医院口腔科,山东济南250000 [3]山东省耳鼻喉医院耳鼻咽喉科,山东济南250022 [4]复旦大学附属儿科医院分子医学中心,上海201102

出　　处：《上海口腔医学》2025年第1期59-67,共9页Shanghai Journal of Stomatology

基　　金：上海交通大学医学院附属第九人民医院生物样本库项目(YBKA202202);2022年九院优秀研究型医师培育项目(2022yxyjxys-lc);上海交通大学医学院附属第九人民医院临床研究助推计划(JYLJ202114)。

摘　　要：目的:研究一个中国常染色体显性钙化不全型釉质发育不全家系的致病基因,并报道该家系2例患者的多学科联合治疗过程,为遗传性釉质发育不全的遗传咨询和临床治疗提供指导。方法:收集先证者及其家系成员的临床资料及外周血,进行全外显子组测序,通过数据分析,筛选出可能的致病基因;通过Sanger测序和蛋白质三维结构预测进行验证。结果:该遗传家系中患病成员全口牙冠呈黄褐色,牙面粗糙,釉质剥脱磨损,符合钙化不全型釉质发育不全。在先证者及其母亲、妹妹的测序结果中发现了FAM83H基因第5外显子存在c.1363C>T无义突变,该突变预测会导致FAM83H蛋白发生截断突变(p.Gln455^(*)),家系中未患病成员未发现上述突变。先证者及其妹妹接受以正畸为基础的多学科治疗,口腔功能和美观恢复。结论:本研究首次在一个中国家系中发现了导致常染色体显性钙化不全型釉质发育不全的FAM83H基因无义突变位点c.1363C>T(p.Gln455^(*)),进一步验证和补充了导致釉质发育不全的FAM83H突变位点。釉质发育不全患者可以通过多种正畸和修复治疗方式,恢复口腔功能及美观。PURPOSE:To investigate the pathogenic gene of one Chinese family with autosomal dominant hypocalcified amelogenesis imperfecta and to report multidisciplinary treatment process for two patients from this family,so as to provide guidance for genetic counseling and clinical treatment of hereditary amelogenesis imperfecta.METHODS:The clinical data and peripheral blood of the family members were collected.Whole-exome sequencing was performed,and candidate variants were filtered out by data analysis.The identified variant was confirmed by Sanger sequencing and protein three-dimensional structure prediction.RESULTS:Affected members of this hereditary family exhibited yellow-brown discoloration of the dental crowns,rough tooth surfaces,and enamel erosion,consistent with hypocalcified amelogenesis imperfecta.A nonsense mutation c.1363C>T(p.Gln455^(*))in exon 5 of the FAM83H gene was identified in the proband,her mother,and her sister;this mutation was predicted to cause a truncation of the FAM83H protein.This variant was not found in unaffected family members.After receiving multidisciplinary treatment based on orthodontics,the proband and her sister restored oral function and aesthetics.CONCLUSIONS:The nonsense variant of FAM83H caused hypocalcified amelogenesis imperfecta in this study is detected for the first time in a Chinese family.The results further validate the pathogenic variant involved in FAM83H leading to amelogenesis imperfecta.Patients with amelogenesis imperfecta can restore oral function and aesthetics through various orthodontic and restorative treatments.

关 键 词：常染色体显性钙化不全型釉质发育不全 FAM83H基因 全外显子组测序 多学科治疗 

分 类 号：R782.1[医药卫生—口腔医学]