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Familial Cancer

, Volume 18, Issue 3, pp 311–315 | Cite as

Phenotypic confirmation of oligodontia, colorectal polyposis and cancer in a family carrying an exon 7 nonsense variant in the AXIN2 gene

  • Catherine BeardEmail author
  • Rebecca Purvis
  • Ingrid M. Winship
  • Finlay A. Macrae
  • Daniel D. Buchanan
Short Communication

Abstract

The AXIN2 gene, like APC, plays a role in the Wnt signalling pathway involved in colorectal tumour formation. Heterozygous mutations in AXIN2 have been shown to cause ectodermal dysplasia (including tooth agenesis, or more specifically, oligodontia), and, in some carriers, colorectal cancer and/or adenomatous polyposis develops. There is a paucity of published AXIN2 families making genotype-phenotype (polyposis, colorectal cancer and oligodontia) correlations challenging. In this case report we describe a family with c.1972delA, p.Ser658Alafs*31 nonsense variant in AXIN2 where the three confirmed carriers presented with both oligodontia and colorectal adenomatous polyposis; mean number of teeth missing in carriers was 16.5 (range 11–22) and mean number of polyps in carriers was 49 (range 5->100, polyps were predominantly adenomatous). This highlights the importance of confirming phenotypic information in familial polyposis, to guide appropriate genetic investigations, as well as providing additional phenotypic and penetrance data to aid in clinical risk management recommendations. Our experience supports the inclusion of AXIN2 on panels for testing of patients with polyposis.

Keywords

AXIN2 Polyposis Oligodontia Colorectal neoplasia Ectodermal dysplasia 

Notes

Acknowledgements

Dr Ved Berani, Healthy Smiles Dental Group, Blackburn South, Victoria, Australia. Dr Wayland Wang, The Royal Melbourne Hospital, Parkville, Victoria, Australia.

Funding

Daniel D. Buchanan is a University of Melbourne Research at Melbourne Accelerator Program (R@MAP) Principal Research Fellow and NHMRC R.D. Wright Career Development Fellow.

Compliance with ethical standards

Conflict of interest

The authors declare they hold no conflict of interest with respect to this work.

Informed consent

Family members engaged with the Parkville Familial Cancer Centre gave verbal consent to the publication of non-identifiable details.

References

  1. 1.
    Polakis P (2007) The many ways of Wnt in cancer. Curr Opin Genet Dev 17(1):45–51CrossRefGoogle Scholar
  2. 2.
    Seidensticker MJ, Behrens J (2000) Biochemical interactions in the wnt pathway. Biochim Biophys Acta 1495(2):168–182CrossRefGoogle Scholar
  3. 3.
    Marvin ML, Mazzoni SM, Herron CM et al (2011) AXIN2-associated autosomal dominant ectodermal dysplasia and neoplastic syndrome. Am J Med Genet A 155a(4):898–902CrossRefGoogle Scholar
  4. 4.
    Galiatsatos P, Foulkes WD (2006) Familial adenomatous polyposis. Am J Gastroenterol 101(2):385–398CrossRefGoogle Scholar
  5. 5.
    Letra A, Menezes R, Granjeiro JM, Vieira AR (2009) AXIN2 and CDH1 polymorphisms, tooth agenesis, and oral clefts. Birth Defects Res A Clin Mol Teratol 85(2):169–173CrossRefGoogle Scholar
  6. 6.
    Bergendal B, Klar J, Stecksén-Blicks C et al (2011) Isolated oligodontia associated with mutations in EDARADD, AXIN2, MSX1, and PAX9 genes. Am J Med Genet Part A 155(7):1616–1622CrossRefGoogle Scholar
  7. 7.
    Liu H, Ding T, Zhan Y, Feng H (2015) A novel AXIN2 missense mutation is associated with non-syndromic oligodontia. PLoS ONE 10(9):e0138221CrossRefGoogle Scholar
  8. 8.
    Lammi L, Arte S, Somer M et al (2004) Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet 74(5):1043–1050CrossRefGoogle Scholar
  9. 9.
    Rivera B, Perea J, Sanchez E et al (2014) A novel AXIN2 germline variant associated with attenuated FAP without signs of oligondontia or ectodermal dysplasia. Eur J Hum Genet 22(3):423–426CrossRefGoogle Scholar
  10. 10.
    Richards S, Aziz N, Bale S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–424CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Parkville Familial Cancer CentreThe Royal Melbourne Hospital and Peter MacCallum Cancer CentreParkvilleAustralia
  2. 2.Department of MedicineUniversity of Melbourne, The Royal Melbourne HospitalParkvilleAustralia
  3. 3.Colorectal Medicine and GeneticsThe Royal Melbourne HospitalParkvilleAustralia
  4. 4.Colorectal Oncogenomics Group, Department of Clinical PathologyThe University of MelbourneParkvilleAustralia
  5. 5.University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer CentreParkvilleAustralia

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