NOVEL MUTATIONS IN PAX9 GENE ASSOCIATED WITH DENTAL ANOMALIES- A REVIEW
DOI:
https://doi.org/10.61841/zacd6e65Keywords:
Homeobox genes, Mutation, Orofacial clef, PAX9, Polymorphism, Tooth agenesisAbstract
Dental anomalies such as tooth agenesis are caused by disturbances and gene mutations that occur during odontogenesis. Human genetic variations have long been of researchers’ interest, as they are partly responsible for the inter-individual response to drugs, infections, and several other phenotypes related to the development and progression of the disease. Tooth development is an intricate process that involves a complex interplay of genes acting in symphony to exhibit the trait. Mutations or genetic errors in the DNA sequences encoding proteins involved in the process of odontogenesis have been identified in recent years. Some of the genes of prime importance are the homeobox genes, which are known to play an important role in tooth development. Several genes, such as PAX, MSX, AXIN, and DLX, have been implicated in the process of odontogenesis. Animal models used in earlier studies reported that PAX9-deficient knockout mice exhibit missing molars due to an arrest of tooth development at the bud stage. The aim of this review was to prepare an exhaustive collection of PAX9 mutation panels reported to be associated with dental anomalies. The literature review will also provide a comprehensive understanding of variations observed in the PAX9 gene in association with several common dental anomalies.
Downloads
References
1. Thomas BL, Sharpe PT. Patterning of the murine dentition by homeobox genes. European Journal of Oral Sciences. 1998;106(Suppl 1):48–54.
2. Duverger O, Morasso MI. Role of homeobox genes in the patterning, specification, and differentiation of ectodermal appendages in mammals. J Cell Physiol. 2008;216(2):337‐346. doi:10.1002/jcp.21491
3. Laura Bull, Genetics, Mutations, and Polymorphisms - Madame Curie Bioscience Database, 2013.
4. Peters H, Neubüser A, Balling R. Pax genes and organogenesis: Pax9 meets tooth development. Eur J Oral Sci. 1998;106 Suppl 1:38‐43. doi:10.1111/j.1600-0722.1998.tb02151.x
5. Vitria EE, Tofani I, Kusdhany L, Bachtiar EW. Genotyping analysis of the Pax9 Gene in patients with Maxillary canine impaction. F1000Res. 2019;8:254. Published 2019 Mar 5. doi:10.12688/f1000research.17147.1
6. Bonczek O, Balcar VJ, Šerý O. PAX9 gene mutations and tooth agenesis: A review. Clin Genet. 2017; 92(5): 467‐476. doi: 10.1111/cge.12986
7. Zhang W, Qu HC, Zhang Y. PAX-9 polymorphism may be a risk factor for hypodontia: a meta-analysis.
Genet Mol Res. 2014;13(4):9997‐10006. Published 2014 Nov 28. doi:10.4238/2014.November.28.4
8. Šerý O, Bonczek O, Hloušková A, et al. A screen of a large Czech cohort of oligodontia patients implicates a
novel mutation in the PAX9 gene. Eur J Oral Sci. 2015;123(2):65‐71. doi:10.1111/eos.12170
9. Citak M, Cakici EB, Benkli YA, Cakici F, Bektas B, Buyuk SK. Dental anomalies in an orthodontic patient
population with maxillary lateral incisor agenesis. Dental Press J Orthod. 2016;21(6):98‐102. doi:10.1590/2177-
6709.21.6.098-102.oar
10. Liu H, Ding T, Zhan Y, Feng H. A Novel AXIN2 Missense Mutation Is Associated with Non-Syndromic
Oligodontia. PLoS One. 2015;10(9):e0138221. Published 2015 Sep 25. doi:10.1371/journal.pone.0138221
11. Yu M, Wong SW, Han D, Cai T. Genetic analysis: Wnt and other pathways in nonsyndromic tooth agenesis.
Oral Dis. 2019;25(3):646‐651. doi:10.1111/odi.12931
12. Wong SW, Han D, Zhang H, et al. Nine Novel PAX9 Mutations and a Distinct Tooth Agenesis Genotype-Phenotype. J Dent Res. 2018;97(2):155‐162. doi:10.1177/002203451772932.
13. Fauzi NH, Ardini YD, Zainuddin Z, Lestari W. A review on non-syndromic tooth agenesis associated with
PAX9 mutations. Jpn Dent Sci Rev. 2018;54(1):30‐36. doi:10.1016/j.jdsr.2017.08.001
14. Murakami A, Yasuhira S, Mayama H, Miura H, Maesawa C, Satoh K. Characterization of PAX9 variant
P20L was identified in a Japanese family with tooth agenesis. PLoS One. 2017;12(10):e0186260. Published 2017
Oct 12. doi:10.1371/journal.pone.0186260
15. Salvi A, Giacopuzzi E, Bardellini E, et al. Mutation analysis by direct and whole exome sequencing in
familial and sporadic tooth agenesis. Int J Mol Med. 2016;38(5):1338‐1348. doi:10.3892/ijmm.2016.2742
16. Abu-Siniyeh A, Khabour OF, Owais AI. The role of PAX9 promoter gene polymorphisms in causing
Hypodontia: a study in the Jordanian population. Appl Clin Genet. 2018;11:145‐149. Published 2018 Nov 21.
doi:10.2147/TACG.S183212
17. Yang L, Liang J, Yue H, Bian Z. Two novel mutations in MSX1 causing oligodontia. PLoS One.
2020;15(1):e0227287. Published 2020 Jan 8. doi:10.1371/journal.pone.0227287
18. Mártha K, Kerekes Máthé B, Moldovan VG, Bănescu C. Study of rs12532, rs8670 Polymorphism of Msh
Homeobox 1 (MSX1), rs61754301, rs4904155 Polymorphism of Paired Box Gene 9 (PAX9), and rs2240308
Polymorphism of Axis Inhibitor Protein 2 (AXIN2) Genes in Nonsyndromic Hypodontia. Biomed Res Int.
2019; 2019: 2183720. Published 2019 Nov 5. doi:10.1155/2019/2183720
19. Rodrigues AS, Teixeira EC, Antunes LS, et al. Association between craniofacial morphological patterns and
tooth agenesis-related genes. Prog Orthod. 2020;21(1):9. Published 2020 Apr 6. doi:10.1186/s40510-020-
00309-5
20. Arandi NZ, Mustafa S. Maxillary lateral incisor agenesis; a retrospective cross-sectional study. Saudi Dent, J.
2018;30(2):155‐160. doi:10.1016/j.sdentj.2017.12.006
21. Koskinen S, Keski-Filppula R, Alapulli H, Nieminen P, Anttonen V. Familial oligodontia and regional
odontodysplasia associated with a PAX9 initiation codon mutation. Clin Oral Investig. 2019;23(11):4107‐4111.
doi:10.1007/s00784-019-02849-5
22. Mitsui SN, Yasue A, Masuda K, et al. Novel PAX9 mutations cause non-syndromic tooth agenesis. J Dent
Res. 2014;93(3):245‐249. doi:10.1177/0022034513519801
23. Kirac D, Eraydin F, Avcilar T, et al. Effects of PAX9 and MSX1 gene variants to hypodontia, tooth size and
the type of congenitally missing teeth. Cell Mol Biol (Noisy-le-grand). 2016;62(13):78‐84. Published 2016 Nov
30. doi:10.14715/cmb/2016.62.13.14
24. Hlousková A, Bonczek O, Izakovicová-Hollá L, et al. Novel PAX9 gene polymorphisms and mutations and
susceptibility to tooth agenesis in the Czech population. Neuro Endocrinol Lett. 2015;36(5):452‐457.
25. Howe BJ, Cooper ME, Vieira AR, et al. Spectrum of Dental Phenotypes in Nonsyndromic Orofacial
Clefting. J Dent Res. 2015;94(7):905‐912. doi:10.1177/0022034515588281
26. Jia S, Zhou J, Fanelli C, et al. Small-molecule Wnt agonists correct cleft palates in Pax9 mutant mice in
utero. Development. 2017;144(20):3819‐3828. doi:10.1242/dev.157750
27. Li C, Lan Y, Krumlauf R, Jiang R. Modulating Wnt Signaling Rescues Palate Morphogenesis in Pax9
Mutant Mice. J Dent Res. 2017;96(11):1273‐1281. doi:10.1177/0022034517719865
28. Devi MSA, Padmanabhan S. Role of polymorphisms of MSX1 and PAX9 genes in palatal impaction of
maxillary canines. J Orthod. 2019;46(1):14‐19. doi:10.1177/1465312518820537
29. Xiong Z, Ren S, Chen H, et al. PAX9 regulates squamous cell differentiation and carcinogenesis in the oroesophageal epithelium. J Pathol. 2018;244(2):164‐175. doi:10.1002/path.4998
30. Smiline Girija AS, Vijayashree Priyadharsini J, Paramasivam Arumugam. CLSI-based antibiogram profile
and the detection of MDR and XDR strains of Acinetobacter baumannii isolated from urine samples. Medical
Journal of the Islamic Republic of Iran. 2019; 33(3); 11-16
31. Smiline Girija AS, Vijayashree Priyadharsini J, Paramasivam Arumugam. Prevalence of VIM and GIM
producing Acinetobacter baumannii from patients with severe UTI. Acta microbiologica et immunologica
Hungarica 2018; 16(8): 1-12.
32. Smiline Girija AS, Vijayashree Priyadharsini J, Paramasivam Arumugam. Molecular characterization of
plasmid-encoded blaTEM, blaSHV and blaCTX-M among extended spectrum β-lactamases [ESBL] producing
Acinetobacter baumannii. British Journal of biomedical sciences. 2018; 16(8): 1-3
33. Paramasivam A, Vijayashree Priyadharsini J, Raghunandhakumar S. N6-adenosine methylation (m6A): a
promising new molecular target in hypertension and cardiovascular diseases. Hypertens Res. 2020;43(2):
153‐154.
34. Vijayashree Priyadharsini J, Smiline Girija AS, Paramasivam A. An insight into the emergence of
Acinetobacter baumannii as an oro-dental pathogen and its drug resistance gene profile—an in silico approach.
Heliyon. 2018;4(12):e01051.
35. Vijayashree Priyadharsini J, Smiline Girija AS, Paramasivam A. In silico analysis of virulence genes in an
emerging dental pathogen A. baumannii and related species. Arch Oral Biol. 2018;94:93‐98.
36. Sohaib Shahzan M, Smiline Girija AS, Vijayashree Priyadharsini J. A computational study targeting the
mutated L321F of ERG11 gene in C. albicans, associated with fluconazole resistance with bioactive compounds
from Acacianilotica. J Mycol Med. 2019;29(4): 303‐309. doi:10.1016/j.mycmed.2019.100899
37. Ashwin K S, Muralidharan N P. Vancomycin-resistant enterococcus (VRE) vs Methicillin-resistant
Staphylococcus Aureus (MRSA). Indian J Med Microbiol 2015;33, Suppl S1:166-7
38. Smiline Girija AS, Vijayashree Priyadhasini J, Paramasivam Arumugam. Plasmid-encoded dfrA-1, dfrA-5,
Sul1 and Sul2 mediated trimethoprim-sulfamethoxazole [TMP-SMX] resistance among Acinetobacter
baumannii isolated from urine samples of patients with severe UTI. Journal of Global Antimicrobial
Resistance. 2019: 17: 145-46
39. Renuka, S., & Muralidharan, N. P. (2017, February 1). Comparison of benefits of herbal mouthwashes with
Chlorhexidine mouthwash: A review. Asian Journal of Pharmaceutical and Clinical Research
40. Shahana, R.Y., Muralidharan, N.P., Efficacy of mouth rinse in maintaining oral health of patients attending
orthodontic clinics, Research Journal of Pharmacy and Technology, 9(11), 1991-1993
41. Marickar R, Geetha R V, Neelakandan P, Kurian M, Efficacy of contemporary and novel intracanal
medicaments against Enterococcus faecalis, Journal of Clinical Pediatric Dentistry (2014) 39(1) 47-50
42. Ashwatha Pratha, A., Geetha, R.V., Awareness on hepatitis-B vaccination among dental students-A
questionnaire survey, Research Journal of Pharmacy and Technology, vol 10(5)1360-1362
43. Vaishali, M., Geetha, R.V., Antibacterial activity of orange peel oil on Streptococcus mutans and
Enterococcus: An In Vitro Study, Research Journal of Pharmacy and Technology, vol. 11(2), 513-514.
44. Maajida Aafreen, M., Geetha, R.V., Thangavelu, L., Evaluation of antiinflammatory action of laurus
nobilis-an in vitro study, International Journal of Research in Pharmaceutical Sciences, vol. vol10(2),1209-1213.
Downloads
Published
Issue
Section
License
Copyright (c) 2020 AUTHOR
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format for any purpose, even commercially.
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
- The licensor cannot revoke these freedoms as long as you follow the license terms.
Under the following terms:
- Attribution — You must give appropriate credit , provide a link to the license, and indicate if changes were made . You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Notices:
You do not have to comply with the license for elements of the material in the public domain or where your use is permitted by an applicable exception or limitation .
No warranties are given. The license may not give you all of the permissions necessary for your intended use. For example, other rights such as publicity, privacy, or moral rights may limit how you use the material.
