Axis inhibition protein 2 polymorphisms may be a risk factor for families with isolated oligodontia

Qin,Han; Cai,Jun

doi:10.3892/mmr.2014.2900

Axis inhibition protein 2 polymorphisms may be a risk factor for families with isolated oligodontia

Authors:
- Han Qin
- Jun Cai
View Affiliations

Affiliations: Department of Stomatology, The First People's Hospital of Lianyungang City, Lianyungang, Jiangsu 222002, P.R. China, Department of Anesthesia, The Third People's Hospital of Lianyungang City, Lianyungang, Jiangsu 222006, P.R. China
Published online on: November 7, 2014 https://doi.org/10.3892/mmr.2014.2900
Pages: 1899-1904

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The objective of the present study was to search for Msh homeobox 1 (MSX1), paired box gene 9 (PAX9), ectodysplasin‑A (EDA) and axis inhibition protein 2 (AXIN2) variants in a family with isolated oligodontia and analyse the pathogenesis of mutations that result in oligodontia phenotypes. Members of a single family (but of different descent) with oligodontia and unrelated healthy controls were enrolled in our study. Genomic DNA was isolated from blood samples. Mutation analysis was performed by amplifying MSX1, PAX9, EDA and AXIN2 exons as well as their exon‑intron boundaries and sequencing the products. DNA sequencing of the AXIN2 gene revealed three mutations in the two patients with oligodontia: a homozygotic silent mutation c.1365A>G (p.Pro455=) in exon 3, two c.956+16A>G mutations (II‑1: homozygosis; III‑1: heterozygosis) and c.1200+71A>G (homozygosis) in the intron, which possibly contributed to structural and functional changes in proteins. The heterozygotic mutations c.1365A>G and c.1200+71A>G were identified in the proband's mother (II‑2). No mutations were detected in the MSX1, PAX9 and EDA genes of oligodontia patients. The findings suggest that the c.956+16A>G, c.1365A>G and c.1200+71A>G mutations of AXIN2 may be responsible for the oligodontia phenotype in this family, but these findings require further study.

View Figures

View References

1	Matalova E, Fleischmannova J, Sharpe PT and Tucker AS: Tooth agenesis: from molecular genetics to molecular dentistry. J Dent Res. 87:617–623. 2008. View Article : Google Scholar : PubMed/NCBI
2	Cudney SM and Vieira AR: Molecular factors resulting in tooth agenesis and contemporary approaches for regeneration: a review. Eur Arch Paediatr Dent. 13:297–304. 2012. View Article : Google Scholar : PubMed/NCBI
3	Lammi L, Arte S, Somer M, et al: Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet. 74:1043–1050. 2004. View Article : Google Scholar : PubMed/NCBI
4	Swinnen S, Bailleul-Forestier I, Arte S, et al: Investigating the etiology of multiple tooth agenesis in three sisters with severe oligodontia. Orthod Craniofac Res. 11:24–31. 2008. View Article : Google Scholar : PubMed/NCBI
5	Jia S, Zhou J, Gao Y, et al: Roles of Bmp4 during tooth morphogenesis and sequential tooth formation. Development. 140:423–432. 2013. View Article : Google Scholar :
6	Bailleul-Forestier I, Molla M, Verloes A and Berdal A: The genetic basis of inherited anomalies of the teeth: Part 1. Clinical and molecular aspects of non-syndromic dental disorders. Eur J Med Genet. 51:273–291. 2008. View Article : Google Scholar : PubMed/NCBI
7	Wang J, Jian F, Chen J, et al: Sequence analysis of PAX9, MSX1 and AXIN2 genes in a Chinese oligodontia family. Arch Oral Biol. 56:1027–1034. 2011. View Article : Google Scholar : PubMed/NCBI
8	Bergendal B, Klar J, Stecksén-Blicks C, et al: Isolated oligodontia associated with mutations in EDARADD, AXIN2, MSX1, and PAX9 genes. Am J Med Genet A. 155:1616–1622. 2011. View Article : Google Scholar
9	Gunbay T, Koyuncu BO, Sipahi A, et al: Multidisciplinary approach to a nonsyndromic oligodontia patient using advanced surgical techniques. Int J Periodontics Restorative Dent. 31:297–305. 2011.PubMed/NCBI
10	Nakatomi M, Wang XP, Key D, et al: Genetic interactions between Pax9 and Msx1 regulate lip development and several stages of tooth morphogenesis. Dev Biol. 340:438–449. 2010. View Article : Google Scholar : PubMed/NCBI
11	De Coster PJ, Marks LA, Martens LC and Huysseune A: Dental agenesis: genetic and clinical perspectives. J Oral Pathol Med. 38:1–17. 2009. View Article : Google Scholar
12	Letra A, Menezes R, Granjeiro JM, et al: AXIN2 and CDH1 polymorphisms, tooth agenesis, and oral clefts. Birth Defects Res A Clin Mol Teratol. 85:169–173. 2009. View Article : Google Scholar :
13	Mostowska A, Biedziak B and Jagodzinski PP: Axis inhibition protein 2 (AXIN2) polymorphisms may be a risk factor for selective tooth agenesis. J Hum Genet. 51:262–266. 2006. View Article : Google Scholar : PubMed/NCBI
14	Liang J, Song G, Li Q, et al: Novel missense mutations in PAX9 causing oligodontia. Arch Oral Biol. 57:784–789. 2012. View Article : Google Scholar : PubMed/NCBI
15	Vieira AR: Oral clefts and syndromic forms of tooth agenesis as models for genetics of isolated tooth agenesis. J Dent Res. 82:162–165. 2003. View Article : Google Scholar : PubMed/NCBI
16	Zhang YD, Chen Z, Song YQ, et al: Making a tooth: growth factors, transcription factors, and stem cells. Cell Res. 15:301–316. 2005. View Article : Google Scholar : PubMed/NCBI
17	Amen M, Liu X, Vadlamudi U, et al: PITX2 and β-catenin interactions regulate lef-1 isoform expression. Mol Cel Biol. 27:7560–7573. 2007. View Article : Google Scholar
18	Kangas AT, Evans AR, Thesleff I, et al: Nonindependence of mammalian dental characters. Nature. 432:211–214. 2004. View Article : Google Scholar : PubMed/NCBI
19	Küchler EC, Lips A, Tannure PN, et al: Tooth agenesis association with self-reported family history of cancer. J Dent Res. 92:149–155. 2013. View Article : Google Scholar
20	Paixao-Cortes VR, Braga T, Salzano FM, et al: PAX9 and MSX1 transcription factor genes in non-syndromic dental agenesis. Arch Oral Biol. 56:337–344. 2011. View Article : Google Scholar
21	Menezes R, Marazita ML, Goldstein McHenry T, et al: AXIS inhibition protein 2, orofacial clefts and a family history of cancer. J Am Dent Assoc. 140:80–84. 2009. View Article : Google Scholar : PubMed/NCBI
22	Ruhin-Poncet B, Ghoul-Mazgar S, Hotton D, et al: Msx and dlx homeogene expression in epithelial odontogenic tumors. J Histochem Cytochem. 57:69–78. 2009. View Article : Google Scholar :
23	Kapadia H, Mues G and D’Souza R: Genes affecting tooth morphogenesis. Orthod Craniofac Res. 10:105–113. 2007. View Article : Google Scholar : PubMed/NCBI
24	Ovári G, Molnár B, Tarján I, et al: Gene polymorphisms in periodontitis and hypodontia: methodological basis of investigations. Fogorv Sz. 100:266–272. 259–265. 2007.PubMed/NCBI
25	Townsend G, Bockmann M, Hughes T, et al: Genetic, environmental and epigenetic influences on variation in human tooth number, size and shape. Odontology. 100:1–9. 2012. View Article : Google Scholar
26	Wang J and Abate-Shen C: Transcriptional repression by the Msx1 homeoprotein is associated with global redistribution of the H3K27me3 repressive mark to the nuclear periphery. Nucleus. 3:155–161. 2012. View Article : Google Scholar : PubMed/NCBI
27	Pani SC: The genetic basis of tooth agenesis: basic concepts and genes involved. J Indian Soc Pedod Prev Dent. 29:84–89. 2011. View Article : Google Scholar : PubMed/NCBI
28	dos Pinheiro RS, Otero RA, Portela MB and Castro GF: Severe oligodontia and dental anomalies in a child with a history of multiple natal teeth: An eight-year retrospective. Gen Dent. 59:e248–e250. 2011.
29	Bural C, Oztas E, Ozturk S, et al: Multidisciplinary treatment of non-syndromic oligodontia. Eur J Dent. 6:218–226. 2012.PubMed/NCBI