Wu J Y, Yu M, Sun S C, Fan Z Z, Zheng J L, Zhang L T, Feng H L, Liu Y, Han D
Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Disease & National Engineering Laboratory for Digital Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China.
Department of Dental Implantology & Prosthetic Dentistry, Shen-zhen Stomatology Hospital, Shenzhen 518001, Guangdong, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2020 Dec 9;53(1):24-33. doi: 10.19723/j.issn.1671-167X.2021.01.005.
To detect the () gene mutation in patients with hypohidro-tic ectodermal dysplasia (HED), and to analyze the distribution pattern of missing permanent teeth and the systemic manifestation of HED patients with gene mutation.
Twelve HED families were enrolled from clinic for genetic history collection, systemic physical examination and oral examination. Peripheral blood or saliva samples were collected from the probands and the family members to extract genomic DNA. PCR amplification and Sanger sequencing were utilized to detect the gene variations, which were compared with the normal sequence (NM_001399.5). The functional impact of gene variants was then evaluated by functional prediction of mutation, conservation analysis and protein structure prediction. The pathogenicity of each gene variation was assessed according to the stan-dards and guidelines of the American College of Medical Genetics and Genomics (ACMG). The systemic phenotype and missing permanent tooth sites of HED patients with gene mutations were summarized, and the missing rate of each tooth position was analyzed and compared.
Eight out of twelve HED families were identified to carry gene mutations, including: c.164T>C(p.Leu55Pro); c.457C>T (p.Arg153Cys); c.466C>T(p.Arg156Cys); c. 584G>A(p.Gly195Glu); c.619delG(p.Gly207Profs73); c.673C>T(p.Pro225Ser); c.676C>T(p.Gln226) and c.905T>G(p.Phe302Cys). Among them, c.164T>C(p.Leu55Pro); c.619delG(p.Gly207Profs73); c.673C>T(p.Pro225Ser); c.676C>T(p.Gln226) and c.905T>G(p.Phe302Cys) were novel mutations. The HED patients with gene mutations in this study were all male. Our results showed that the average number of missing permanent teeth was 13.86±4.49, the average number of missing permanent teeth in the upper jaw was 13.14±5.76, the missing rate was 73.02%. And in the lower jaw, the average number of missing permanent teeth was 14.57±3.05, the missing rate was 80.95%. There was no significant difference in the number of missing teeth between the left and right sides of the permanent dentition (>0.05). Specifi-cally, the maxillary lateral incisors, the maxillary second premolars and the mandibular lateral incisors were more likely to be missing, while the maxillary central incisors, the maxillary and mandibular first molars had higher possibility of persistence.
This study detected novel gene pathogenic variants and summarized the distribution pattern of missing permanent teeth of HED patients, thus enriched the variation and phenotype spectrum of gene, and provided new clinical evidence for genetic diagnosis and prenatal consultation.
检测少汗型外胚层发育不良（HED）患者的（）基因突变，分析恒牙缺失的分布模式以及基因突变的HED患者的全身表现。
从门诊招募12个HED家系，收集遗传病史、进行全身体格检查和口腔检查。从先证者及其家庭成员采集外周血或唾液样本以提取基因组DNA。利用聚合酶链反应（PCR）扩增和桑格测序检测（）基因变异，并与正常序列（NM_001399.5）进行比较。然后通过突变功能预测、保守性分析和蛋白质结构预测评估（）基因变异的功能影响。根据美国医学遗传学与基因组学学会（ACMG）的标准和指南评估每个（）基因变异的致病性。总结基因突变的HED患者的全身表型和恒牙缺失部位，分析并比较每个牙位的缺失率。
12个HED家系中有8个被鉴定携带（）基因突变，包括：c.164T>C（p.Leu55Pro）；c.457C>T（p.Arg153Cys）；c.466C>T（p.Arg156Cys）；c.584G>A（p.Gly195Glu）；c.619delG（p.Gly207Profs73）；c.673C>T（p.Pro225Ser）；c.676C>T（p.Gln226）和c.905T>G（p.Phe302Cys）。其中，c.164T>C（p.Leu55Pro）；c.619delG（p.Gly207Profs73）；c.673C>T（p.Pro225Ser）；c.676C>T（p.Gln226）和c.905T>G（p.Phe302Cys）为新突变。本研究中基因突变的HED患者均为男性。结果显示，恒牙平均缺失数为13.86±4.49颗，上颌恒牙平均缺失数为13.14±5.76颗，缺失率为73.02%。下颌恒牙平均缺失数为14.57±3.05颗，缺失率为80.95%。恒牙列左右两侧缺失牙数无显著差异（>0.05）。具体而言，上颌侧切牙、上颌第二前磨牙和下颌侧切牙更易缺失，而上颌中切牙、上颌和下颌第一磨牙存留的可能性较高。
本研究检测到新的（）基因致病变异，总结了HED患者恒牙缺失的分布模式，丰富了（）基因的变异和表型谱，为基因诊断和产前咨询提供了新的临床证据。
