Advertisement

Journal of Genetics

, Volume 97, Issue 5, pp 1169–1177 | Cite as

WNT10A variants in relation to nonsyndromic hypodontia in eastern Slovak population

  • D. GrejtakovaEmail author
  • D. Gabrikova-Dojcakova
  • I. Boronova
  • L. Kyjovska
  • J. Hubcejova
  • M. Fecenkova
  • M. Zigova
  • M. Priganc
  • J. Bernasovska
Research Article

Abstract

Nonsyndromic hypodontia is a congenital absence of less than six permanent teeth, with a most common subtype maxillary lateral incisor agenesis (MLIA). Mutations in several genes have been described in severe tooth agenesis. The aim of this study was to search for the variants in wingless-type MMTV-integration site family member (WNT10A), paired box 9 (PAX9) and axis inhibitor 2 (AXIN2) genes, and investigate their potential role in the pathogenesis of non-syndromic hypodontia. Clinical examination and panoramic radiograph were performed in the cohort of 60 unrelated Slovak patients of Caucasian origin with nonsyndromic hypodontia including 37 MLIA cases and 48 healthy controls. Genomic DNA was isolated from buccal swabs and Sanger sequencing of WNT10A, PAX9 and AXIN2 was performed. Altogether, we identified 23 single-nucleotide variants, of which five were novel. We have found three rare nonsynonymous variants in WNT10A (p.Gly165Arg; p.Gly213Ser and p.Phe228Ile) in eight (13.33%) of 60 patients. Analysis showed potentially damaged WNT10A variant p.Phe228Ile predominantly occurred only in MLIA patients, and with a dominant form of tooth agenesis (odds ratio \(({\hbox {OR}}_{\mathrm{dom}}) = 9.841\); \(P=0.045\); 95% confidence interval (CI) 0.492–196.701; \({\hbox {OR}}_{\mathrm{rec}} = 0.773\); \(P =1.000\); 95% CI 0.015–39.877). In addition, the WNT10A variant p.Phe228Ile showed a trend associated with familial nonsyndromic hypodontia (\(P =0.024\); OR = 1.20; 95% CI 0.97–1.48). After Bonferroni correction, these effects remained with borderline tendencies. Using a 3D WNT10A protein model, we demonstrated that the variant Phe228Ile changes the protein secondary structure. In PAX9 and AXIN2, common variants were detected. Our findings suggest that the identified WNT10A variant p.Phe228Ile could represent risk for the inherited nonsyndromic hypodontia underlying MLIA. However, further study in different populations is required.

Keywords

WNT10A gene PAX9 gene AXIN2 gene tooth agenesis maxillary lateral incisor agenesis 

Notes

Acknowledgements

This publication is the result of the implementation of the projects ITMS 26220120041 and ITMS 26110230100 supported by Research and Development Operational Programme and LPP-0331-09 funded by Slovak Research and Development Agency.

References

  1. Abdalla E. M., Mostowska A., Jagodziński P. P., Dwidar K. and Ismail S. R. 2014 A novel WNT10A mutation causes non-syndromic hypodontia in an Egyptian family. Arch. Oral. Biol. 59, 722–728.CrossRefGoogle Scholar
  2. Adaimy L., Chouery E., Megarbane H., Mroueh S., Delague V., Nicolas E. et al. 2007 Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. Am. J. Hum. Genet. 81, 821–828.CrossRefGoogle Scholar
  3. Alves-Ferreira M., Pinho T., Sousa A., Sequeiros J., Lemos C., and Alonso I. 2014 Identification of genetic risk factors for maxillary lateral incisor agenesis. J. Dent. Res. 93, 452–458.CrossRefGoogle Scholar
  4. Amini F., Rakhshan V. and Babaei P. 2012 Prevalence and pattern of hypodontia in the permanent dentition of 3374 Iranian orthodontic patients. Dent. Res. J. 9, 245–250.Google Scholar
  5. Arte S., Parmanen S., Pirinen S., Alaluusua S. and Nieminen P. 2013 Candidate gene analysis of tooth agenesis identifies novel mutations in six genes and suggests significant role for WNT and EDA signaling and allele combinations. PLoS One 8, e73705.CrossRefGoogle Scholar
  6. Arzoo P. S., Klar J., Bergendal B., Norderyd J. and Dahl N. 2014 WNT10A mutations account for 1/4 of population-based isolated oligodontia and show phenotypic correlations. Am. J. Med. Genet. Part A 164A, 353–359.CrossRefGoogle Scholar
  7. Bergendal B., Klar J., Stecksén-Blicks C., Norderyd J. and Dahl N. 2011 Isolated oligodontia associated with mutations in EDARADD, AXIN2, MSX1 and PAX9 genes. Am. J. Med. Genet. Part A 155, 1616–1622.CrossRefGoogle Scholar
  8. Bohring A., Stamm T., Spaich C., Haase C., Spree K., Hehr U. et al. 2009 WNT10A Mutations are a frequent cause of a broad spectrum of ectodermal dysplasias with sex-biased manifestation pattern in Heterozygotes. Am. J. Hum. Genet. 85, 97–105.CrossRefGoogle Scholar
  9. He H., Han D., Feng H., Qu H., Song S., Bai B. et al. 2013 Involvement of and interaction between WNT10A and EDA mutations in tooth agenesis cases in the Chinese population. PLoS One 8, s.e80393.CrossRefGoogle Scholar
  10. Jumlongras D., Lin J. Y., Chapra A., Seidman C. E., Seidman J. G., Maas R. L. and Olsen B. R. 2004 A novel missense mutation in the paired domain of PAX9 causes nonsyndromic oligodontia. Hum. Genet. 114, 242–249.CrossRefGoogle Scholar
  11. Kantaputra P. and Sripathomsawat W. 2011 WNT10A and isolated hypodontia. Am. J. Med. Genet. 155, 1119–1122.CrossRefGoogle Scholar
  12. Kantaputra P., Kaewgahya M. and Kantaputra W. 2014. WNT10A mutations also associated with agenesis of the maxillary permanent canines, a separate entity. Am. J. Med. Genet. Part A 164A, 360–363.CrossRefGoogle Scholar
  13. Kula K., Trimmell J., Lu Y., Briscoe P. and Feng J. Q. 2008 Tooth agenesis in a family and homozygous PAX9 mutation in exon 3: a case report. World J. Orthod. 9, 55–61.Google Scholar
  14. Lammi L., Arte S., Somer M., Jarvinen H., Lahermo P., Thesleff I. et al. 2004 Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am. J. Hum. Genet. 74, 1043–1050.CrossRefGoogle Scholar
  15. Larmour C. J., Mossey P. A., Thind B. S., Forgie A. H. and Stirrups D. R. 2005 Hypodontia – a retrospective review of prevalence and etiology. Part I. Quintessence Int. 36, 263–270.PubMedGoogle Scholar
  16. Lee W. C., Yamaguchi T., Watanabe C., Kawaguchi A., Takeda M. Kim Y. I. et al. 2012 Association of common PAX9 variants with permanent tooth size variation in non-syndromic East Asian populations. J. Hum. Genet. 57, 654–659.CrossRefGoogle Scholar
  17. Lindor M. N., Win A. K., Gallinger S., Daftary D., Thibodeau S. N., Silva R. and Letra A. 2014 Colorectal cancer and self-reported tooth agenesis. Hered. Cancer Clin. Pract. 12, 7.CrossRefGoogle Scholar
  18. Marcello E., Gardoni F., Di Luca M. and Pérez-Otaño I. 2010 An arginine stretch limits ADAM10 exit from the endoplasmic reticulum. J. Biol. Chem. 285, 10376–10384.CrossRefGoogle Scholar
  19. Mostowska A., Biedziak B. and Jagodzinski P. 2006 Axis inhibition protein 2 (AXIN2) polymorphisms may be a risk factor for selective tooth agenesis. J. Hum. Genet. 51, 262–266.CrossRefGoogle Scholar
  20. Mostowska A., Biedziak B., Zadurska M., Dunin-Wilczynska I., Lianeri M. and Jagodzinski P. 2013 Nucleotide variants of genes encoding components of the Wnt signalling pathway and the risk of non-syndromic tooth agenesis. Clin. Genet. 84, 429–440.CrossRefGoogle Scholar
  21. Mostowska A., Biedziak B., Zaurska M., Matuszewska-Trojan S. and Jagodzinski P. P. 2015 WNT10A coding variants and maxillary lateral incisor agenesis with associated dental anomalies. Eur. J. Oral. Sci. 123, 1–8.CrossRefGoogle Scholar
  22. Mu Y. D., Xu Z., Contreras C. I., McDaniel J. S., Donly K. J. and Chen S. 2013 Mutational analysis of AXIN2, MSX1, and PAX9 in two Mexican oligodontia families. Genet. Mol. Res. 12, 4446–4458.CrossRefGoogle Scholar
  23. Nawaz S., Klar J., Wajid M., Aslam M., Tariq M., Schuster J. et al. 2009 WNT10A missense mutation associated with a complete odonto-onycho-dermal dysplasia syndrome. Eur. J. Hum. Genet. 17, 1600–1605.CrossRefGoogle Scholar
  24. Pandey P., Ansari A., Choudhary K. and Saxena A. 2013 Familial aggregation of maxillary lateral incisor agenesis (MLIA). BMJ Case Rep. ( https://doi.org/10.1136/bcr-2012-007846).
  25. Pawlowska E., Janik-Papis K., Poplawski T., Blasiak J. and Szczepanska J. 2010 Mutations in the PAX9 gene in sporadic oligodontia. Orthod. Craniofac. Res. 13, 142–152.CrossRefGoogle Scholar
  26. Pinho T. 2004 Maxillary superior incisor agenesis. Facial repercussions and familiar study. Thesis, University of Porto.Google Scholar
  27. Pinho T., Silva-Fernandes A., Bousbaa H. and Macie P. 2010 Mutational analysis of MSX1 and PAX9 genes in Portuguese families with maxillary lateral incisor agenesis. Eur. J. Orthod. 32, 582–588.CrossRefGoogle Scholar
  28. Ruoslahti E. 1996 RGD and other recognition sequences for integrins. Annu. Rev. Cell Dev. Biol. 12, 697–715.CrossRefGoogle Scholar
  29. Schalk-van der Weide Y., Steen W. H. and Bosman F. 1992 Distribution of missing teeth and tooth morphology in patients with oligodontia. ASDC J. Dent. Child. 59, 133–140.PubMedGoogle Scholar
  30. Schwartz D. R., Wu R., Kardia S. L., Levin A. M., Huang C. C., Shedden K. A. et al. 2003 Novel candidate targets of beta-catenin/T-cell factor in signaling identified by gene expression profiling of ovarian endometrioid adenocarcinomas. Cancer Res. 63, 2913–2922.PubMedGoogle Scholar
  31. Sheiham A. 2001 Dietary effects on dental diseases. Public Health Nutr. 4, 569–591.PubMedGoogle Scholar
  32. Song S., Zhao R., He H., Zhang J., Feng H. and Lin L. 2014 WNT10A variants are associated with non-syndromic tooth agenesis in the general population. Hum. Genet. 133, 1117–1124.CrossRefGoogle Scholar
  33. Stockton D. W., Das P., Goldenberg M., D’Souza R. N. and Patel P. I. 2000 Mutation of PAX9 is associated with oligodontia. Nat. Genet. 24, 18–19.CrossRefGoogle Scholar
  34. Swinnen S., Bailleul-Forestier I., Arte S., Nieminen P., Devriendt K. and Carels C. 2008 Investigating the etiology of multiple tooth agenesis in three sisters with severe oligodontia. Orthod. Craniofac. Res. 11, 24–31.CrossRefGoogle Scholar
  35. Tao R., Jin B., Guo S. Z., Quing W., Feng G. Y., Brooks D. G. et al. 2006 A novel missense mutation of the EDA gene in a Mongolian family with congenital hypodontia. J. Hum. Genet. 51, 498–502.CrossRefGoogle Scholar
  36. Van den Boogaard M. J., Créton M., Bronkhorst Y., van der Hout A., Hennekam E., Lindhout D. et al. 2012 Mutations in WNT10A are present in more than half of isolated hypodontia cases. J. Med. Genet. 49, 327–331.CrossRefGoogle Scholar
  37. Vastardis H., Karimbux N., Guthua S. W., Seidman J. G. and Seidman C. E. 1996 A human MSX1 homeodomain missense mutation causes selective tooth agenesis. Nat. Genet. 13, 417–442.CrossRefGoogle Scholar
  38. Yang J., Wang S. K., Choi M., Reid B. M., Hu Y., Lee Y. L. et al. 2015 Taurodontism, variations in tooth number, and misshapened crowns in Wnt10a null mice and human kindreds. Mol. Genet. Genomic Med. 3, 40–58.CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2018

Authors and Affiliations

  1. 1.Department of Biology, Faculty of Humanities and Natural SciencesUniversity of PresovPresovSlovakia
  2. 2.Dental Clinic and OrthodonticsKosiceSlovakia

Personalised recommendations