Journal of Prevention and Treatment for Stomatological Diseases ›› 2020, Vol. 28 ›› Issue (4): 257-261.doi: 10.12016/j.issn.2096-1456.2020.04.010

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Research progress on pathogenic genes and molecular mechanisms of nonsyndromic tooth agenesis

XIE Weihong,YU Dongsheng,ZHAO Wei()   

  1. Guanghua School and Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, China
  • Received:2018-12-04 Revised:2019-04-26 Online:2020-04-20 Published:2020-03-31
  • Contact: Wei ZHAO


Tooth agenesis is a common tooth number deficiency that occurs in the tooth-forming process or earlier period of tooth germ development and has a serious impact on the maxillofacial development, aesthetics and masticatory function of patients. According to the presence or absence of systemic symptoms, tooth agenesis can be divided into syndromic tooth agenesis and nonsyndromic tooth agenesis. In recent years, the discovery of new related genes, new mutation sites and related molecular mechanisms has become a major direction of gene research. This article will review the current research progress of the signaling pathways related to nonsyndromic tooth agenesis, such as the WNT/beta-catenin pathway, TGF-β/BMP pathway, PAX9, MSX1, and the EDA/EDAR/NF-κb pathway, and their molecular mechanisms. The interaction between Pax9 activating the Wnt/β-catenin and TGF-β/BMP pathways, MSX1 activating the TGF-β/BMP pathway, and Wnt activating the EDA/EDAR/NF-κb pathway was also found, which provides a new theoretical basis for the prevention and treatment of tooth agenesis. The molecular mechanism of nonsyndromic tooth agenesis is rarely studied; thus, the exploration of its mechanism will become one of the main research directions in the future.

Key words: nonsyndromic tooth agenesis, tooth-forming, gene regulation, signal pathway, pathogenic genes, molecular mechanisms, Wnt/β-catenin, TGF-β/BMP, paired box 9, muscle segment homeobox gene 1

CLC Number: 

  • R78
[1] Song S, Zhao R, He H , et al. WNT10A variants are associated with non-syndromic tooth agenesis in the general population[J]. Hum Genet, 2014,133(1):117-124.
[2] Rakhshan V, Rakhshan H . Meta-analysis of congenitally missing teeth in the permanent dentition: prevalence, variations across ethnicities, regions and time[J]. Int Orthod, 2015,13(3):261-273.
[3] Yu M, Wong SW, Han D , et al. Genetic analysis: Wnt and other pathways in nonsyndromic tooth agenesis[J]. Oral Dis, 2019,25(3):646-651.
[4] HaddajiMastouri M, De Coster P, Zaghabani A , et al. Genetic study of non-syndromic tooth agenesis through the screening of paired box 9, msh homeobox 1, axin 2, and Wnt family member 10A genes: a case-series[J]. Eur J Oral Sci, 2018,126(1):24-32.
[5] Balic A, Thesleff I . Tissue interactions regulating tooth development and renewal[J]. Curr Top Dev Biol, 2015,115:157-186.
[6] Hunter DJ, Bardet C, Mouraret S , et al. Wnt acts as a prosurvival signal to enhance dentin regeneration[J]. J Bone Miner Res, 2015,30(7):1150-1159.
[7] Bergendal B, Klar J, Stecksen-Blicks C , et al. Isolated oligodontia associated with mutations in EDARADD, AXIN2, MSX1, and PAX9 genes[J]. Am J Med Genet A, 2011,155A(7):1616-1622.
[8] Yue H, Liang J, Yang K , et al. Functional analysis of a novel missense mutation in AXIN2 associated with non-syndromic tooth agenesis[J]. Eur J Oral Sci, 2016,124(3):228-233.
[9] Zeng B, Zhao Q, Li S , et al. Novel EDA or EDAR mutations identified in patients with X-linked hypohidrotic ectodermal dysplasia or non-syndromic tooth agenesis[J]. Genes (Basel), 2017,8(10):259.
[10] Yu P, Yang W, Han D , et al. Mutations in WNT10B are identified in individuals with oligodontia[J]. Am J Hum Genet, 2016,99(1):195-201.
[11] Massink MP, Creton MA, Spanevello F , et al. Loss-of-function mutations in the WNT co-receptor LRP6 cause autosomal-dominant oligodontia[J]. Am J Hum Genet, 2015,97(4):621-626.
[12] Kantaputra PN, Hutsadaloi A, Kaewgahya M , et al. WNT10B mutations associated with isolated dental anomalies[J]. Clin Genet, 2018,93(5):992-999.
[13] Huckert M, Stoetzel C, Morkmued S , et al. Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta[J]. Hum Mol Genet, 2015,24(11):3038-3049.
[14] Lee KE, Ko J, Shin TJ , et al. Oligodontia and curly hair occur with ectodysplasin-a mutations[J]. J Dent Res, 2014,93(4):371-375.
[15] Tallon-Walton V, Manzanares-Cespedes MC, Carvalho-Lobato P , et al. Exclusion of PAX9 and MSX1 mutation in six families affected by tooth agenesis. A genetic study and literature review[J]. Med Oral Patol Oral Cir Bucal, 2014,19(3):e248-254.
[16] Wong SW, Han D, Zhang H , et al. Nine novel PAX9 mutations and a distinct tooth agenesis genotype-phenotype[J]. J Dent Res, 2018,97(2):155-162.
[17] Gaczkowska A, Abdalla EM, Dowidar KM , et al. De novo EDA mutations: variable expression in two Egyptian families[J]. Arch Oral Biol, 2016,68:21-28.
[18] Paradowska-Stolarz A . MSX1 gene in the etiology orofacial deformities[J]. Postepy Hig Med Dosw (Online), 2015,69:1499-1504.
[19] Gerits A, Nieminen P, De Muynck S , et al. Exclusion of coding region mutations in MSX1, PAX9 and AXIN2 in eight patients with severe oligodontia phenotype[J]. Orthod Craniofac Res, 2006,9(3):129-136.
[20] 秦晗, 徐宏志, 龚永庆 . 单纯性多数牙缺失家系的AXIN2基因突变分析[J]. 口腔疾病防治, 2016,24(12):706-710.
Qin H, Xu HZ, Gong YQ . Analysis of AXIN2 gene mutations in a family with isolated oligodontia[J]. J Prev Treat Stomatol Dis, 2016,24(12):706-710.
[21] Srivastava AK, Montonen O, Saarialho-Kere U , et al. Fine mapping of the EDA gene: a translocation breakpoint is associated with a CpG island that is transcribed[J]. Am J Hum Genet, 1996,58(1):126-132.
[22] Cluzeau C, Hadj-Rabia S, Jambou M , et al. Only four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases[J]. Hum Mutat, 2011,32(1):70-72.
[23] He F, Wang H, Zhang X , et al. Conservation analysis and pathogenicity prediction of mutant genes of ectodysplasin a[J]. BMC Med Genet, 2018,19(1):209.
[24] Pina-Aguilar RE, Gonzalez-Ortega C, Calull-Bago A , et al. Combined preimplantation genetic testing for aneuploidy and monogenic disease in a mexican family affected by X-linked hypohidrotic ectodermal dysplasia[J]. Rev Invest Clin, 2018,70(4):164-168.
[25] Shimomura Y, Wajid M, Weiser J , et al. Identification of mutations in the EDA and EDAR genes in Pakistani families with hypohidrotic ectodermal dysplasia[J]. Clin Genet, 2009,75(6):582-584.
[26] Wang H, Xie LS . Novel nonsense mutation of the EDA gene in a Chinese family with X-linked hypohidrotic ectodermal dysplasia[J]. J Dermatol, 2014,41(11):1014-1016.
[27] Kurihara Y, Hayashi R, Watanabe E , et al. Novel EDA hemizygous frame-shift mutation c. 731delG (p.R244Qfs*36) underlies hypohidrotic ectodermal dysplasia in a Japanese family[J]. J Dermatol, 2014,41(12):1110-1112.
[28] Li D, Xu R, Huang F , et al. A novel missense mutation in collagenous domain of EDA gene in a Chinese family with X-linked hypohidrotic ectodermal dysplasia[J]. J Genet, 2015,94(1):115-119.
[29] Huang SX, Liang JL, Sui WG , et al. EDA mutation as a cause of hypohidrotic ectodermal dysplasia: a case report and review of the literature[J]. Genet Mol Res, 2015,14(3):10344-10351.
[30] Zeng B, Xiao X, Li S , et al. Eight mutations of three genes (EDA, EDAR, and WNT10A) identified in seven hypohidrotic ectodermal dysplasia patients[J]. Genes (Basel), 2016,7(9):65.
[31] Wang J, Sun K, Shen Y , et al. DNA methylation is critical for tooth agenesis: implications for sporadic non-syndromic anodontia and hypodontia[J]. Sci Rep, 2016,6:19162.
[32] Jia S, Zhou J, Fanelli C , et al. Small-molecule Wnt agonists correct cleft palates in Pax9 mutant mice in utero[J]. Development, 2017,144(20):3819-3828.
[33] 程忠委, 宋庆高 . Sp基因与Wnt基因对胚胎发育异常及唇腭裂的影响[J]. 口腔疾病防治, 2019,27(6):396-399.
Cheng ZW, Song QG . The effects of the Sp and Wnt genes on abnormalities in embryonic developmental and cleft lip and palate[J]. J Prev Treat Stomatol Dis, 2019,27(6):396-399.
[34] Yin W, Bian Z . The gene network underlying hypodontia[J]. J Dent Res, 2015,94(7):878-885.
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