Kanchanasevee Charinya, Sriwattanapong Kanokwan, Theerapanon Thanakorn, Thaweesapphithak Sermporn, Chetruengchai Wanna, Porntaveetus Thantrira, Shotelersuk Vorasuk
Geriatric Dentistry and Special Patients Care International Program, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Genomics and Precision Dentistry Research Unit, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Front Physiol. 2020 Nov 19;11:573214. doi: 10.3389/fphys.2020.573214. eCollection 2020.
Tooth agenesis is one of the most common orodental anomalies that demonstrate phenotypic and genotypic heterogeneity with a prevalence of 2.5%-7%. Mutations in have been proposed to be the most common cause of nonsyndromic tooth agenesis (NSTA). The aim of this study was to characterize the dental features and genetic variants of NSTA in a Thai population. We recruited 13 unrelated patients with NSTA who attended the Faculty of Dentistry, Chulalongkorn University, Thailand, from 2017 to 2019. All 13 underwent whole exome sequencing that identified likely pathogenic genetic variants, all in , in five patients. All five patients had second premolar agenesis, while three also had absent or peg-shaped upper lateral incisors. Patient 1 possessed a novel heterozygous duplication, c.916_918dupAAC (p.Asn306dup) in Patients 2 and 3 harbored a heterozygous and homozygous c.637G > A (p.Gly213Ser) in , respectively. Patients 4 possessed a heterozygous c.511C > T (p.Arg171Cys) in . Patient 5 harbored a homozygous c.511C > T (p.Arg171Cys) in and a novel heterozygous c.413A > T (p.Asn138Ile) in , suggesting digenic inheritance. We recruited another 18 family members of these five patients. Out of 23 participants, homozygous variants were identified in 2 patients and heterozygous variants in 17 individuals. Both homozygous patients had NSTA. Eight out of 17 heterozygous individuals (8/17) had NSTA or a peg-shaped lateral incisor, indicating a 47% penetrance of the heterozygous variants or 53% (10/19) penetrance of either homozygous or heterozygous variants in . The frequencies of the c.511C > T in our in-house 1,876 Thai exome database, Asian populations, and non-Asian populations were 0.016, 0.005-0.033, and 0.001, respectively; while those of the c.637G > A were 0.016, 0.004-0.029, and 0.000, respectively. In conclusion, our study reports two novel variants with one each in and , expanding the genotypic spectra of NSTA. Second premolar agenesis is a common phenotype in affected individuals with variants in ; however, its penetrance is incomplete. Lastly, the different frequencies of variants, c.511C > T and c.637G > A, in diverse populations might contribute to the prevalence range of NSTA between continents.
牙齿发育不全是最常见的口腔颌面部异常之一，具有表型和基因型异质性，患病率为2.5%-7%。已提出 中的突变是非综合征性牙齿发育不全（NSTA）最常见的原因。本研究的目的是描述泰国人群中NSTA的牙齿特征和基因变异。我们招募了13名2017年至2019年在泰国朱拉隆功大学牙科学院就诊的无关NSTA患者。所有13名患者均接受了全外显子组测序，其中5名患者鉴定出可能的致病基因变异，均在 中。所有5名患者均有第二前磨牙发育不全，而3名患者还伴有上颌侧切牙缺失或呈钉状。患者1在 中存在一个新的杂合重复，c.916_918dupAAC（p.Asn306dup）。患者2和3在 中分别携带杂合和纯合的c.637G > A（p.Gly213Ser）。患者4在 中存在一个杂合的c.511C > T（p.Arg171Cys）。患者5在 中携带一个纯合的c.511C > T（p.Arg171Cys）和一个新的杂合的c.413A > T（p.Asn138Ile），提示双基因遗传。我们招募了这5名患者的另外18名家庭成员。在23名参与者中，2名患者鉴定出纯合 变异，17名个体鉴定出杂合变异。两名纯合患者均患有NSTA。17名杂合个体中有8名（8/17）患有NSTA或钉状侧切牙，表明杂合变异的外显率为47%，或 中纯合或杂合变异的外显率为53%（10/19）。我们内部的1876个泰国外显子组数据库、亚洲人群和非亚洲人群中c.511C > T的频率分别为0.016、0.005-0.033和0.001；而c.637G > A的频率分别为0.016、0.004-0.029和0.000。总之，我们的研究报告了两个新变异，分别在 和 中各有一个，扩展了NSTA的基因型谱。第二前磨牙发育不全是 变异患者中常见的表型；然而，其外显率不完全。最后，不同人群中 变异c.511C > T和c.637G > A的不同频率可能导致各大洲之间NSTA患病率的差异。
