Skip to main content

Advertisement

SpringerLink
Log in

Sequencing analysis of exons 5 and 6 in RUNX2 in non-syndromic patients with supernumerary tooth in Kelantan, Malaysia

  • Original Article
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Objective

The aim of this study is to do a sequencing analysis of RUNX2 in non-syndromic patients with supernumerary tooth.

Materials and methods

Fifty-three patients with supernumerary tooth were identified retrospectively from 1,275 radiographic reviews who attended the Hospital Universiti Sains Malaysia (USM) Dental Clinic. Informed consent was obtained from the patients prior to the study. Blood samples were collected from 41 patients and DNA extractions were performed out of which 10 samples were chosen randomly for PCR amplification using designated primers for RUNX2 followed by DNA sequencing analysis.

Results

This study involved 28 male patients (68.3%) and 13 female patients (31.7%) with a gender ratio of 2.2:1 and mean age of 15.9 ± 6.2 years. DNA extraction yielded ~ 40 ng/μl of concentrated DNA, and each DNA sample had more than 1500 bp of DNA length. The purity ranged between 1.8 and 2.0. DNA sequencing analysis did not reveal any mutations in exons 5 and 6 of RUNX2.

Conclusion

This study did not reveal any mutations in exons 5 and 6 of RUNX2 in non-syndromic patients with supernumerary tooth.

Clinical relevance

Analysis of mutations in RUNX2 is important to enhance the understanding of tooth development in humans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Scheiner MA, Sampson WJ (1997) Supernumerary teeth: a review of the literature and four case reports. Aust Dent J 42(3):160–165

    Article  PubMed  Google Scholar 

  2. Rajab LD, Hamdan MA (2002) Supernumerary teeth: review of the literature and a survey of 152 cases. Int J Paediatr Dent 12(4):244–254

    Article  PubMed  Google Scholar 

  3. Yusof WZ (1990) Non-syndrome multiple supernumerary teeth: literature review. J Can Dent Assoc 56(2):147–149

    PubMed  Google Scholar 

  4. Bodin I, Julin P, Thomsson M (1978) Frequency and distribution of supernumerary teeth among 21609 patients. Dentomaxillofac Radiol 7(1):15–17

    Article  PubMed  Google Scholar 

  5. Fleming PS, Xavier GM, DiBiase AT, Cobourne MT (2010) Revisiting the supernumerary: the epidemiological and molecular basis of extra teeth. Br Dent J 208(1):25–30

    Article  PubMed  Google Scholar 

  6. Oropeza L, Sánchez R, López A (2020) Supernumerary as an etiological factor in the alteration of the sequence and dental eruption. Oral Health Dental Sci 4(1):1–6

    Google Scholar 

  7. Proff P, Fanghanel J, Allegrini S Jr, Bayerlein T, Gedrange T (2006) Problems of supernumerary teeth, hyperdontia or dentes supernumerarii. Ann Anat 188(2):163–169

    Article  PubMed  Google Scholar 

  8. Gardiner JH (1961) Supernumerary teeth. Trans Br Soc Study Orthod 12(1):63–75

    Google Scholar 

  9. Anthonappa RP, Omer RS, King NM (2008) Characteristics of 283 supernumerary teeth in southern Chinese children. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105(6):E48–E54

    Article  PubMed  Google Scholar 

  10. Brook AH (1984) A unifying aetiological explanation for anomalies of human tooth number and size. Arch Oral Biol 29(5):373–378

    Article  PubMed  Google Scholar 

  11. Wang XX, Zhang J, Wei FC (2007) Autosomal dominant inherence of multiple supernumerary teeth. Int J Oral Maxillofac Surg 36(8):756–758

    Article  PubMed  Google Scholar 

  12. El-Toum S, Cassia A, Zaarour I, Hobeika P, Feki A (2008) Is the homozygous region on chromosome 16q12.2 responsible for a fifth mandibular incisor? Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105(6):767–771

    Article  PubMed  Google Scholar 

  13. Bei M (2009) Molecular genetics of tooth development. Curr Opin Genet Dev 19(5):504–510

    Article  PubMed  PubMed Central  Google Scholar 

  14. Brook AH (2009) Multilevel complex interactions between genetic, epigenetic and environmental factors in the aetiology of anomalies of dental development. Arch Oral Biol 54(Supp 1):S3–S17

    Article  PubMed  PubMed Central  Google Scholar 

  15. Desai RS, Shah NP (1998) Multiple supernumerary teeth in two brothers: a case report. J Oral Pathol Med 27(8):411–413

    Article  PubMed  Google Scholar 

  16. Gallas MM, Garcia A (2000) Retention of permanent incisors by mesiodens: a family affair. Br Dent J 188(2):63–64

    Article  PubMed  Google Scholar 

  17. D’Souza RN, Klein OD (2007) Unraveling the molecular mechanisms that lead to supernumerary teeth in mice and men: current concepts and novel approaches. Cells Tissues Organs 186(1):60–69

    Article  PubMed  Google Scholar 

  18. Zhang Z, Lan Y, Chai Y, Jiang R (2009) Antagonistic actions of MSX1 and OSR2 pattern mammalian teeth into a single row. Science 323(5918):1232–1234

    Article  PubMed  PubMed Central  Google Scholar 

  19. Brook AH (1974) Dental anomalies of number, form and size: their prevalence in British school children. J Int Assoc Dent Child 5(2):37–53

    PubMed  Google Scholar 

  20. Thesleff I (2003) Developmental biology and building a tooth. Quintessence Int 34(8):613–620

    PubMed  Google Scholar 

  21. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997) OSF2/CBFA1: a transcriptional activator of osteoblast differentiation. Cell 89(5):747–754

    Article  PubMed  Google Scholar 

  22. Camilleri S, McDonald F (2006) RUNX2 and dental development. Eur J Oral Sci 114(5):361–373

    Article  PubMed  Google Scholar 

  23. Pratap J, Galindo M, Zaidi SK et al (2003) Cell growth regulatory role of RUNX2 during proliferative expansion of preosteoblasts. Cancer Res 63(17):5357–5362

    PubMed  Google Scholar 

  24. Wang XP, Aberg T, James MJ, Levanon D, Groner Y, Thesleff I (2005) RUNX2 (CBFA1) inhibits Shh signalling in the lower but not upper molars of mouse embryos and prevents the budding of putative successional teeth. J Dent Res 84(2):138–143

    Article  PubMed  Google Scholar 

  25. Åberg T (2006) The function of BMPs and RUNX2 in normal tooth development and in the pathogenesis of cleidocranial dysplasia. University of Helsinki, Helsinki

    Google Scholar 

  26. Quack I, Vonderstrass B, Stock M et al (1999) Mutation analysis of core binding factor A1 in patients with cleidocranial dysplasia. Am J Hum Genet 65(5):1268–1278

    Article  PubMed  PubMed Central  Google Scholar 

  27. Levanon D, Negreanu V, Bernstein Y, Bar-Am I, Avivi L, Groner Y (1994) AML1, AML2, and AML3, the human members of the runt domain gene-family: cDNA structure, expression, and chromosomal localization. Genomics 23(2):425–432

    Article  PubMed  Google Scholar 

  28. Xiao ZS, Liu SG, Hinson TK, Quarles LD (2001) Characterization of the upstream mouse Cbfa1/Runx2 promoter. J Cell Biochem 82(4):647–659

    Article  PubMed  Google Scholar 

  29. Chen S, Gluhak-Heinrich J, Wang YH et al (2009) Runx2, Osx, and Dspp in tooth development. J Dent Res 88(10):904–909

    Article  PubMed  PubMed Central  Google Scholar 

  30. D’Souza RN, Aberg T, Gaikwad J et al (1999) Cbfa1 is required for epithelial-mesenchymal interactions regulating tooth development in mice. Development 126(13):2911–2920

    Article  PubMed  Google Scholar 

  31. Mundlos S, Otto F, Mundlos C et al (1997) Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell 89(5):773–779

    Article  PubMed  Google Scholar 

  32. Otto F, Kanegane H, Mundlos S (2002) Mutations in the RUNX2 gene in patients with cleidocranial dysplasia. Hum Mutat 19(3):209–216

    Article  PubMed  Google Scholar 

  33. Currall V, Clancy R, Dimond D, Amirfeyz R, Kershaw C, Gargan M (2007) Cleidocranial dysplasia. Curr Orthop 21(2):159–162

    Article  Google Scholar 

  34. Bailleul-Forestier I, Berdal A, Vinckier F, de Ravel T, Fryns JP, Verloes A (2008) The genetic basis of inherited anomalies of the teeth. Part 2: syndromes with significant dental involvement. Eur J Med Genet 51(5):383–408

    Article  PubMed  Google Scholar 

  35. Jensen BL, Kreiborg S (1990) Development of the dentition in cleidocranial dysplasia. J Oral Pathol Med 19(2):89–93

    Article  PubMed  Google Scholar 

  36. Li Y, Pan W, Xu W et al (2009) RUNX2 mutations in Chinese patients with cleidocranial dysplasia. Mutagenesis 24(5):425–431

    Article  PubMed  PubMed Central  Google Scholar 

  37. Tessa A, Salvi S, Casali C et al (2003) Six novel mutations of the RUNX2 gene in Italian patients with cleidocranial dysplasia. Hum Mutat 22(1):104

    Article  PubMed  Google Scholar 

  38. Kobayashi I, Kiyoshima T, Wada H et al (2006) Type II/III Runx2/Cbfa1 is required for tooth germ development. Bone 38(6):836–844

    Article  PubMed  Google Scholar 

  39. Cobourne MT, Miletich I, Sharpe PT (2004) Restriction of sonic hedgehog signalling during early tooth development. Development 131(12):2875–2885

    Article  PubMed  Google Scholar 

  40. Wang XP, O’Connell DJ, Lund JJ et al (2009) Apc inhibition of Wnt signalling regulates supernumerary tooth formation during embryogenesis and throughout adulthood. Development 136(11):1939–1949

    Article  PubMed  PubMed Central  Google Scholar 

  41. Yoshida T, Kanegane H, Osato M et al (2002) Functional analysis of RUNX2 mutations in Japanese patients with cleidocranial dysplasia demonstrates novel genotype-phenotype correlations. Am J Hum Genet 71(4):724–738

    Article  PubMed  PubMed Central  Google Scholar 

  42. Zou SJ, D’Souza RN, Ahlberg T, Bronckers AL (2003) Tooth eruption and cementum formation in the Runx2/Cbfa1 heterozygous mouse. Arch Oral Biol 48(9):673–677

    Article  PubMed  Google Scholar 

  43. Zhou G, Chen Y, Zhou L et al (1999) CBFA1 mutation analysis and functional correlation with phenotypic variability in cleidocranial dysplasia. Human Mol Genet 8(12):2311–2316

    Article  Google Scholar 

  44. Garvey MT, Barry HJ, Blake M (1999) Supernumerary teeth - an overview of classification, diagnosis and management. J Can Dent Assoc 65(11):612–616

    PubMed  Google Scholar 

  45. Ohazama A, Courtney J-M, Sharpe P (2004) Opg, Rank, and Rankl in tooth development: co-ordination of odontogenesis and osteogenesis. J Dent Res 83(3):241–244

    Article  PubMed  Google Scholar 

  46. Åberg T, Cavender A, Gaikwad JS et al (2004) Phenotypic changes in dentition of RUNX2 homozygote-null mutant mice. J Histochem Cytochem 52(1):131–139

  47. Åberg T, Wang X-P, Kim J-H, et al. (2004) Runx2 mediates FGF signaling from epithelium to mesenchyme during tooth morphogenesis. Dev Biol 270(1):76-93

Download references

Funding

This study was financially supported by Universiti Sains Malaysia Short Term Grant (304/PPSG/61311087).

Author information

Authors and Affiliations

  1. Department of Pediatric Dentistry, Hospital Raja Permaisuri Bainun, 30450, Ipoh, Perak, Malaysia

    Suhailiza Saharudin

  2. School of Dental Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia

    Sarliza Yasmin Sanusi & Kannan Thirumulu Ponnuraj

  3. Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia

    Kannan Thirumulu Ponnuraj

Authors
  1. Suhailiza Saharudin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarliza Yasmin Sanusi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kannan Thirumulu Ponnuraj
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Suhailiza Saharudin performed the experiments, collected data, and drafted the manuscript. Sarliza Yasmin Sanusi and Kannan Thirumulu Ponnuraj contributed to the conception and study design. Suhailiza Saharudin and Kannan Thirumulu Ponnuraj analyzed the results. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kannan Thirumulu Ponnuraj.

Ethics declarations

Ethics approval

Ethical approval and consent to participate was obtained from Human Research Ethics Committee of Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia (USMKK/PPPP/JEPeM [238.3.(11)]).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Consent for publication

Consent for publication has been obtained by authors and participants involved in this study.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saharudin, S., Sanusi, S.Y. & Ponnuraj, K.T. Sequencing analysis of exons 5 and 6 in RUNX2 in non-syndromic patients with supernumerary tooth in Kelantan, Malaysia. Clin Oral Invest 26, 1261–1268 (2022). https://doi.org/10.1007/s00784-021-04098-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-021-04098-x

Keyword

Search

Navigation