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Familial Cancer

, Volume 18, Issue 2, pp 179–182 | Cite as

NTHL1-associate polyposis: first Australian case report

  • Alexandra GrovesEmail author
  • Margaret Gleeson
  • Allan D. Spigelman
Short Communication
  • 90 Downloads

Abstract

While familial adenomatous polyposis accounts for approximately 1% of all colorectal cancer, the genetic cause underlying the development of multiple colonic adenomas remains unsolved in many patients. Adenomatous polyposis syndromes can be divided into: familial adenomatous polyposis, MUTYH-associated polyposis, polymerase proofreading associated polyposis and the recently described NTHL1-associated polyposis (NAP). NAP is characterised by recessive inheritance, attenuated adenomatous polyposis, colonic cancer(s) and possible extracolonic malignancies. To date, 11 cases have been reported as having germline homozygous or compound heterozygous mutations in the base excision repair gene NTHL1. Here we present a further case of a 65-year-old male with a history of adenomatous polyposis and bladder cancer, who has a previously described homozygous nonsense variant in the NTHL1 gene. This case is consistent with the emerging phenotype previously described of multiple colorectal adenomas and at least one primary tumour, adding to the small but growing body of literature about NAP.

Keywords

NTHL1 Polyposis Colorectal cancer NAP 

Notes

Acknowledgements

We thank the patient for allowing us to report this case.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Shussman N, Wexner SD (2014) Colorectal polyps and polyposis syndromes. Gastroenterol Rep 2(1):1–15CrossRefGoogle Scholar
  2. 2.
    Aretz S (2010) The differential diagnosis and surveillance of hereditary gastrointestinal polyposis syndromes. Dtsch Arztebl Int 107(10):163Google Scholar
  3. 3.
    Weren RD, Ligtenberg MJ, Kets CM et al (2015) A germline homozygous mutation in the base-excision repair gene NTHL1 causes adenomatous polyposis and colorectal cancer. Nat Genet 47(6):668–671CrossRefGoogle Scholar
  4. 4.
    Rivera B, Castellsagué E, Bah I, van Kempen LC, Foulkes WD (2015) Biallelic NTHL1 mutations in a woman with multiple primary tumors. N Engl J Med 373(20):1985–1986CrossRefGoogle Scholar
  5. 5.
    Chubb D, Broderick P, Dobbins SE et al (2016) Rare disruptive mutations and their contribution to the heritable risk of colorectal cancer. Nat Commun 7:11883.  https://doi.org/10.1038/ncomms11883 CrossRefGoogle Scholar
  6. 6.
    Belhadj S, Mur P, Navarro M et al (2017) Delineating the phenotypic spectrum of the NTHL1-associated polyposis. Clin Gastroenterol Hepatol 15(3):461–462CrossRefGoogle Scholar
  7. 7.
    Church J (2016) Polymerase proofreading associated polyposis, and other new syndromes of hereditary colorectal cancer. In: Intestinal polyposis syndromes. Springer, Cham, pp 61–68Google Scholar
  8. 8.
    Broderick P, Bagratuni T, Vijayakrishnan J, Lubbe S, Chandler I, Houlston RS (2006) Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes in familial colorectal cancer predisposition. BMC Cancer 6(1):243CrossRefGoogle Scholar
  9. 9.
    Dallosso AR, Dolwani S, Jones N et al (2008) Inherited predisposition to colorectal adenomas caused by multiple rare alleles of MUTYH but not OGG1, NUDT1, NTH1 or NEIL 1, 2 or 3. Gut 57(9):1252–1255CrossRefGoogle Scholar
  10. 10.
    Khan N, Lipsa A, Arunachal G, Ramadwar M, Sarin R (2017) Novel mutations and phenotypic associations identified through APC, MUTYH, NTHL1, POLD1, POLE gene analysis in Indian familial adenomatous polyposis cohort. Sci Rep 7:2214. https://www.nature.com/articles/s41598-017-02319-6

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Alexandra Groves
    • 1
    Email author
  • Margaret Gleeson
    • 1
  • Allan D. Spigelman
    • 1
    • 2
  1. 1.Hunter Family Cancer ServiceNewcastleAustralia
  2. 2.St Vincent’s Cancer Genetics ClinicUNSW St Vincent’s Clinical School, The Kinghorn Cancer CentreSydneyAustralia

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