Molecular and Genetic Basis of Non-Syndromic Tooth Agenesis
Authors:
L. Kramerová; P. Krejčí; E. Míšová; A. Ševecová
Authors‘ workplace:
Klinika zubního lékařství LF UP a FN, Olomouc
Published in:
Česká stomatologie / Praktické zubní lékařství, ročník 115, 2015, 1, s. 4-12
Category:
Review Article
Overview
Background:
Tooth agenesis represents the most common anomaly of dental development, which according to Online Mendelian Inheritance in Man (OMIM) database, affects approximately 20% of the population. Although the anomaly is so common, the ethiology is still undisclosed. In most cases the agenesis is caused by genetic disorder, only a few develop due to external factors. Some of the external factors are rubeolla, syphilis, vitamin D deficiency or nutritional damage during pregnancy and early childhood. Other harmful factors are radiation therapy in orofacial area in early stages of the development of the patient, harms the mother caused by radiation, chemical substances or drugs (e.g. thalidomide, cytostatics). Local factors include various types of injuries, tumors and osteomyelitis. Hypodontia can occur as an isolated condition (non-syndromic hypodontia) or can be associated with a systemic condition or syndrome (syndromic hypodontia). Despite the fact that, tooth agenesis is so common, little is known about the genetic defects responsible for this complex condition. To date, the genes associated with the non-syndromic form of tooth agenesis, listed in OMIM, are MSX1 (muscle segment homeobox gene 1), PAX9 (paired box gene 9), AXIN2 (axis inhibition protein 2), EDA (ectodysplasin A), WNT10A (Wingless-type MMTV integration site family, member 10A) and LTBP3 (latent transforming growth factor beta binding protein 3). Cases with selective tooth agenesis caused by mutation in genes EDARADD (EDAR-associated death domain), NEMO (nuclear factor-kappaB essential modulator), KRT17 (keratin 17) and TGFA (transforming growth factor-alfa), were also published. All these genes vary both in terms of number of identified mutations and in terms of number of documented patients. These mutations explain the formation of tooth agenesis in only a part of affected individuals. Most patients have no defects in these genes. To select other genes, that are responsible for non-syndromic forms of hypodontia, the identification of genes that cause syndroms with symptoms of hypodontia, seems as reasonable direction of further research.
Keywords:
tooth agenesis – hypodontia – MSX1 – PAX9 – AXIN2 – EDA – WNT10A – LTBP3 – EDARADD – NEMO – KRT17 – TGFA
Sources
1. Artle, S., Nieminen, P., Apajalahti, S., Havvikko, K., Thesleff, I., Pirinen, S.: Characteristics of incisor-premolar hypodonitia in families. J. Dent. Res., roč. 80, 2001, č. 5, s. 1445–1450.
2. Ayub, M., ur-Rehman, F., Yasinzai, M., Ahmad, W.: A novel missense mutation in the ectodysplasin-A (EDA) gene underlies X-linked recessive nonsyndromic hypodontia. Int. J. Dermatol., roč. 49, 2010, č. 12, s. 1399–1402.
3. Bailit, H. L.: Dental variation among populations. An anthropologic view. Dent. Clin. North Amer., roč. 19, 1975, č. 1, s. 125–139.
4. Bergendal, B., Klar, J., Stecksén-Blicks, C., Norderyd, J., Dahl, N.: Isolated oligodontia associated with mutations in EDARADD, AXIN2, MSX1, and PAX9 genes. Am. J. Med. Genet., roč. 155A, 2011, č. 7, s. 1616–1622.
5. Burzynski, N. J., Escobar, V. H.: Classification and genetics of numeric anomalies of dentition. Birth Defects Orig. Artic. Ser., roč. 19, 1983, č. 1, s. 95–106.
6. Callahan, N., Modesto, A., Deeley, K., Meira, R., Vieira, A. R.: Transforming growth factor-alfa gene (TGFA), human tooth agenesis, and evidence of segmental uniparental isodisomy. Eur. J. Oral. Sci., roč. 117, 2009, č. 1, s. 20–26.
7. Clayton, J. M.: Congenital dental anomalies occurring in 3,557 children. ASDC J. Dent. Child., roč. 23, 1956, s. 206–208.
8. De Coster, P. J., Marks, L. A., Martens, L. C., Huysseune, A. Dental agenesis: genetic and clinical perspectives. J. Oral Pathol. Med., roč. 38, 2009, s. 1–17.
9. Fleischmannová, J., Krejčí, P., Matalová, E., Míšek, I.: Molekulární podstata vývoje zubních zárodků. Ortodoncie, roč. 16, 2007, č. 4, s. 39–46.
10. Freire Maia, N.: Ectodermal dysplasias. Hum. Hered., 1971, č. 21, s. 309–312.
11. Freire Maia, N.: Ectodermal dysplasias revisited. Acta Genet. Med. Gemellol., 1977, č. 26, s. 121–131.
12. Galluccio, G., Castellano, M., La Monaca, C.: Genetic basis of non-syndromic anomalies of human tooth number. Arch. Oral. Biol., roč. 57, 2012, č. 7, s. 918–930.
13. Gass, J. K., Wilson, N. J., Smith, F. J., Lane, E. B., McLean, W. H., Rytina, E., Salvary, I., Burrows, N. P.: Steatocystoma multiplex, oligodontia and partial persistent primary dentition associated with a novel keratin 17 mutation. Br. J. Dermatol., roč. 161, 2009, č. 6, 1396–1398.
14. Grahnen, H.: Hypodontia in the permanent dentition: a clinical and genetical investigation. Odontol. Rev., roč. 7, 1956, s. 1–100.
15. Han, D., Gong, Y., Wu, H., Zhang, X., Yan, M., Wang, X., Qu, H., Feng, H., Song, S.: Novel EDA mutation resulting in X-linked non-syndromic hypodontia and the pattern of EDA-associated isolated tooth agenesis. Europ. J. Med. Genet., roč. 51, 2008, č. 6, s. 536–546.
16. Hloušková, A., Bonczek, O., Šerý, O., Lochman, J., Vaněk, J., Černochová, P., Štembírek, J., Krejčí, P., Míšek, I.: Sekvenace části genu pro PAX9 a možná spojitost nalezených polymor-fizmů s agenezí zubů. Ortodoncie, roč. 23, 2014, č. 1, s. 44–51.
17. Chhabra, N., Goswami, M., Chhabra, A.: Genetic basis of dental agenesis - molecular genetics patterning clinical dentistry. Med. Oral. Patol. Oral. Cir. Bucal., roč. 19, 2014, č. 2, s. 112–119.
18. Chishti, M. S., Muhammad, D., Haider, M., Ahmad, W.: A novel missense mutation in MSX1 underlies autosomal recessive oligodontia with associated dental anomalies in Pakistani families. J. Hum. Genet., roč. 51, 2006, č. 10, s. 872–878.
19. Kantaputra, P., Sripathomsawat, W.: WNT10A and isolated hypodontia. Am. J. Med. Genet. A., roč. 155A, 2011, č. 5, s. 1119–1122.
20. Kavitha, B., Priyadharshini, V., Sivapathasundharam, B., Saraswathi, T. R.: Role of genes in oro-dental diseases. Indian J. Dent. Res., roč. 21, 2010, s. 270–274.
21. Kjaer, I.: Cant he location of tooth agenesis and the location of initial bone loss seen in juvenilie periodontitis be explained by neural developmental fields in the jaws? Acta Odontol. Scand., roč. 55, 1997, s. 70–72.
22. Krejčí, P.: Hypodoncie. Souborný referát. Ortodoncie, roč. 15, 2006, č. 3, s. 21–29.
23. Krejčí, P., Fleischmannová, J., Matalová, E., Míšek, I.: Molekulární podstata hypodoncie. Ortodoncie, roč. 16, 2007, č. 1, s. 33–39.
24. Ku, C. L., Dupuis-Girod, S., Dittrich, A. M., Bustamante, J., Santos, O. F., Schulze, I., Bertrand, Y., Couly, G., Bodemer, C., Bossuyt, X., Picard, C., Casanova, J. L.: NEMO mutations in 2 unrelated boys with severe infections and conical teeth. Pediatrics, roč. 115, 2005, č. 5, s. 615–619.
25. Lammi, L., Arte, S., Somer, M., Jarvinen, H., Lahermo, P., Thesleff, I., Pirinen, S., Nieminen, P.: Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am. J. Hum. Genet., roč. 74, 2004, č. 5, s. 1043–1050.
26. Marková, M., Vášková, J.: Nový pohled na problematiku hypodoncie. Čs. Stomat., roč. 89, 1989, č. 6, s. 416–424.
27. Mostowska, A., Biedziak, B., Zadurska, M., Dunin-Wilczynska, I., Lianeri, M., Jagodzinski, P. P.: Nucleotide variants of genes encoding components of the WNT signalling pathway and the risk of non-syndromic tooth agenesis. Clin. Genet., roč. 84, 2013, č. 5, s. 429–440.
28. Mostowska, A., Kobielak, A., Trzeciak, W. H.: Molecular basis of non-syndromic tooth agenesis: mutations of MSX1 and PAX9 reflect their role in patterning human dentition. Eur. J. Oral Sciences, roč. 111, 2003, s. 365–370.
29. Mostowska, A., Zadurska, M., Rakowska, A., Lianeri, M., Jagodziński, P. P.: Novel PAX9 mutation associated with syndromic tooth agenesis. Eur. J. Oral. Sci., roč. 121, 2013, č. 5, s. 403–411.
30. Neubuser, A., Peters, H., Balling, R., Martin, G. R.: Antagonistic interactions between FGF and BMP signaling pathways: a mechanism for positioning the sites of tooth formation. Cell, roč. 90, 1997, č. 2, s. 247–255.
31. Nieminen, P.: Genetic basis of tooth agenesis. J. Exp. Zool. B. Mol. Dev. Evol., roč. 312B, 2009, č. 4, s. 320–342.
32. Noor, A., Windpassinger, C., Vitcu, I., Orlic, M., Rafiq, M. A., Khalid, M., Malik, M. N., Ayub, M., Alman, B., Vincent, J. B.: Oligodontia is caused by mutation in LTBP3, the gene encoding latent TGF-beta binding protein 3. Am. J. Hum. Genet., roč. 84, 2009, č. 4, s. 519–523.
33. Ogawa, T., Kapadia, H., Feng, J. Q., Raghow, R., Peters, H., D‘Souza, R. N.: Functional consequences of interactions between PAX9 and MSX1 genes in normal and abnormal tooth development. J. Biol. Chem., roč. 27, 2006, č. 281, s. 18363–18369.
34. Parkin, N., Elcock, C., Smith, R. N., Griffin, R. C., Brook, A. H.: The aetiology of hypodontia: The prevalence, severity and location of hypodontia within families. Arch. Oral Biol., roč. 54, 2009, č. 1, s. 52–56.
35. Rasool, M., Schuster, J., Aslam, M., Tariq, M., Ahmad, I., Ali, A., Entesarian, M., Dahl, N., Baig, S. M.: A novel missense mutation in the EDA gene associated with X-linked recessive isolated hypodontia. J. Hum. Genet., roč. 53, 2008, č. 10, s. 894–898.
36. Ruf, S., Klimas, D., Hönemann, M., Jabir, S.: Genetic back-ground of nonsyndromic oligodontia: a systematic review and meta-analysis. J. Orofac. Orthop., roč. 74, 2013, č. 4, s. 295–308.
37. Song, S., Zhao, R., He, H., Zhang, J., Feng, H., Lin, L.: WNT10A variants are associated with non-syndromic tooth agenesis in the general population. Hum. Genet., roč. 133, 2014, č. 1, s. 117–124.
38. Sottner, L., a kol. Genetika pro studující stomatologie, 1. vyd. Praha, Pedagogické nakladatelství, 1981.
39. Sottner, L., Racek, J., Švábová-Sládková, M.: Nové poznatky v etiologii hypodoncie, 1. část. Čes. Stomat., roč. 96, 1996, č. 1, s. 4–8.
40. Sottner, L., Racek, J., Švábová-Sládková, M.: Nové poznatky v etiologii hypodoncie, 2. část. Čes. Stomat., roč. 96, 1996, č. 2, s. 50–59.
41. Stockton, D. W., Das, P., Goldenberg, M., D‘Souza, R. N., Patel, P. I.: Mutation of PAX9 is associated with oligodontia. Nat. Genet., roč., 24, 2000, č. 1, s. 18–19.
42. Stritzel, F., Symons, A. L, Gage, J. P.: Agenesis of the second premolar in males and females: distribution, number and sites affected. J. Clin. Pediatr. Dent., roč.15, 1990, č. 1, s. 39–41.
43. Suarez, B. K., Spence, M. A.: The genetics of hypodontia. J. Dent. Res., roč. 53, 1974, č. 4, s. 781–785.
44. Svinhufvud, E., Myllarniemi, S., Norio, R.: Dominant inheritance of tooth malpositions and their association to hypodontia. Clin. Genet., roč. 34, 1988, s. 373–381.
45. Tallón-Walton, V., Manzanares-Céspedes, M. C, Carvalho-Lobato, P., Valdivia-Gandur, I., Arte, S., Nieminen, P.: Exclusion of PAX9 and MSX1 mutation in six families affected by tooth agenesis. A genetic study and literature review. Med. Oral. Patol. Oral. Cir. Bucal., roč. 19, 2014, č. 3, s. 248–254.
46. Tan, S. P. K, van Wijk, A. J., Prahl-Andersen, B.: Severe hypodontia: identifying patterns of human tooth genesis. Eur. J. Orthod., roč. 33, 2011, č. 2, s. 150–154.
47. Tao, R., Jin, B., Guo, S. Z., Qing, W., Feng, G. Y., Brooks, D. G., Liu, L., Xu, J., Li, T., Yan, Y., He, L.: A novel missense mutation of the EDA gene in a Mongolian family with congenital hypodontia. J. Hum. Genet., roč. 51, 2006, č. 5, s. 498–502.
48. Tarpey, P., Pemberton, T. J., Stockton, D. W., Das, P., Ninis, V., Edkins, S., Futreal, P. A., Wooster, R., Kamath, S., Nayak, R., Stratton, M. R., Patel, P. I.: A novel gln358glu mutation in ectodysplasin A associated with X-linked dominant incisor hypodontia. Am. J. Med. Genet., roč. 143, 2007, č. 4, s. 390–394.
49. Townsend, G. C., Richards, L., Hughes, T., Pinkerton, S., Schwerdt, W.: Epigenetic influences may explain dental differences in monozygotic twin pairs. Aust. Dent. J., roč. 50, 2005, č. 2, s. 95–100.
50. Van den Boogaard, M. J., Créton, M., Bronkhorst, Y., van der Hout, A., Hennekam, E., Lindhout, D., Cune, M., Ploos van Amstel, H. K.: Mutations in WNT10A are present in more than half of isolated hypodontia cases. J. Med. Genet., roč. 49, 2012, č. 5, s. 327–331.
51. Vastardis, H.: The genetics of human tooth agenesis: New discoveries for understanding dental anomalies. Amer. J. Orthodont. dentofacial Orthop., roč. 117, 2000, č. 6, s. 650–656.
52. Vastardis, H., Karimbux, N., Guthua, S. W., Seidman, J. G., Seideman, C. E.: A human MSX1 homeodomain missense mutation causes selective tooth agenesis. Nat. Genet., roč. 13, 1996, č. 4, s. 417–421.
53. Vieira, A. R., Meira, R., Modesto, A., Murray, J. C.: MSX1, PAX9, and TGFA contribute to tooth agenesis in humans. J. Dent. Res., roč. 83, 2004, č. 9, s. 723–727.
54. Visinoni, A. F., Lisboa-Costa, T., Pagnan, N. A. B., Chautard-Freire-Maia, E .A.: Ectodermal dysplasias: Clinical and molecular review. Amer. J. Med, Genet., 2009, Part A 149A, s. 1980–2002.
55. Závadová, A.: Ageneze dolních druhých premolárů, část 1. Úvod do problematiky; epidemiologie a etiologie agenezí, diagnostika. Ortodoncie, roč. 11, 2002, č. 2, s. 21–28.
56. Zengin, A., Sumer, A., Karaarslan, E.: Impacted primary tooth and tooth agenesis: a case report of monozygotic twins. Eur. J. Dent., 2008, č. 2, s. 299–302.
57. http://ghr.nlm.nih.gov/
58. http://omim.org/entry
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