Skip to main content

Advertisement

SpringerLink
Log in

Gonadal mosaicism and familial adenomatous polyposis

  • Published:
Familial Cancer Aims and scope Submit manuscript

Abstract

De novo mutations in the adenomatous polyposis coli (APC) gene are estimated to constitute approximately 25% of familial adenomatous polyposis (FAP) cases. A small percentage of these arise in the mosaic form, affecting only a subset of cells in the affected individual. A family is described here whereby an unaffected mother with no detectible mutation in APC, transmitted the identical APC c.4729G>T (p.Glu1577X) mutation to two children. A third child, with the same APC allelic haplotype received a normal APC allele, suggesting that the mutation originated in the gonadal tissues of the mother. These results underscore the utility of mutation-specific genetic testing for the parents and siblings of a proband of an adult-onset disease, even if the proband appears to have a de novo mutation. Parents who test negative for the mutation should be counseled about the possibility of having another affected child due to gonadal mosaicism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

Familial adenomatous polyposis:

FAP

Adenomatous polyposis coli:

APC

References

  1. Petersen GM, Slack J, Nakamura Y (1991) Screening guidelines and premorbid diagnosis of familial adenomatous polyposis using linkage. Gastroenterology 100(6):1658–1664 Jun

    PubMed  CAS  Google Scholar 

  2. Burt RW (2003) Gastric fundic gland polyps. Gastroenterology 125(5):1462–1469 Nov

    Article  PubMed  Google Scholar 

  3. Kadmon M, Tandara A, Herfarth C (2001) Duodenal adenomatosis in familial adenomatous polyposis coli. A review of the literature and results from the Heidelberg Polyposis Register. Int J Colorectal Dis 16(2):63–75 Apr

    Article  PubMed  CAS  Google Scholar 

  4. Cetta F, Curia MC, Montalto G et al (2001) Thyroid carcinoma usually occurs in patients with familial adenomatous polyposis in the absence of biallelic inactivation of the adenomatous polyposis coli gene. J Clin Endocrinol Metab 86(1):427–432 Jan

    Article  PubMed  CAS  Google Scholar 

  5. Cetta F, Montalto G, Gori M, Curia MC, Cama A, Olschwang S (2000) Germline mutations of the APC gene in patients with familial adenomatous polyposis-associated thyroid carcinoma: results from a European cooperative study. Journal of Clin Endocrinol Metabolism 85(1):286–292 Jan

    Article  CAS  Google Scholar 

  6. Wallace MH, Phillips RK (1998) Upper gastrointestinal disease in patients with familial adenomatous polyposis. Br J Surg 85(6):742–750 Jun

    Article  PubMed  CAS  Google Scholar 

  7. Rustin RB, Jagelman DG, McGannon E, Fazio VW, Lavery IC, Weakley FL (1990) Spontaneous mutation in familial adenomatous polyposis. Dis Colon Rectum 33(1):52–55 Jan

    Article  PubMed  CAS  Google Scholar 

  8. Davidson S, Leshanski L, Rennert G, Eidelman S, Amikam D (2002) Maternal mosaicism for a second mutational event—a novel deletion—in a familial adenomatous polyposis family harboring a new germ-line mutation in the alternatively spliced-exon 9 region of APC. Hum Mutat 19(1):83–84 Jan

    Article  PubMed  CAS  Google Scholar 

  9. Niu DM, Huang JY, Li HY et al (2006) Paternal gonadal mosaicism of NIPBL mutation in a father of siblings with Cornelia de Lange syndrome. Prenat Diagn 26(11):1054–1057 Nov

    Article  PubMed  Google Scholar 

  10. Depienne C, Arzimanoglou A, Trouillard O et al (2006) Parental mosaicism can cause recurrent transmission of SCN1A mutations associated with severe myoclonic epilepsy of infancy. Hum Mutat 27(4):389 Apr

    Article  PubMed  Google Scholar 

  11. Gennaro E, Santorelli FM, Bertini E et al (2006) Somatic and germline mosaicisms in severe myoclonic epilepsy of infancy. Biochem Biophys Res Commun 341(2):489–493 Mar 10

    Article  PubMed  CAS  Google Scholar 

  12. Byers PH, Tsipouras P, Bonadio JF, Starman BJ, Schwartz RC (1988) Perinatal lethal osteogenesis imperfecta (OI type II): a biochemically heterogeneous disorder usually due to new mutations in the genes for type I collagen. Am J Hum Genet 42(2):237–248 Feb

    PubMed  CAS  Google Scholar 

  13. Cohen-Solal L, Bonaventure J, Maroteaux P (1991) Dominant mutations in familial lethal and severe osteogenesis imperfecta. Hum Genet 87(3):297–301 Jul

    Article  PubMed  CAS  Google Scholar 

  14. Grange DK, Balfour IC, Chen SC, Wood EG (1998) Familial syndrome of progressive arterial occlusive disease consistent with fibromuscular dysplasia, hypertension, congenital cardiac defects, bone fragility, brachysyndactyly, and learning disabilities. Am J Med Genet 75(5):469–480 Feb 17

    Article  PubMed  CAS  Google Scholar 

  15. Lund AM, Nicholls AC, Schwartz M, Skovby F (1997) Parental mosaicism and autosomal dominant mutations causing structural abnormalities of collagen I are frequent in families with osteogenesis imperfecta type III/IV. Acta Paediatr 86(7):711–718 Jul

    Article  PubMed  CAS  Google Scholar 

  16. Raghunath M, Mackay K, Dalgleish R, Steinmann B (1995) Genetic counselling on brittle grounds: recurring osteogenesis imperfecta due to parental mosaicism for a dominant mutation. Eur J Pediatr 154(2):123–129 Feb

    Article  PubMed  CAS  Google Scholar 

  17. Somprasit C, Aguinaga M, Cisneros PL et al (2004) Paternal gonadal mosaicism detected in a couple with recurrent abortions undergoing PGD: FISH analysis of sperm nuclei proves valuable. Reprod Biomed Online 9(2):225–230 Aug

    Article  PubMed  Google Scholar 

  18. den Dunnen JT, Antonarakis SE (2000) Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion. Hum Mutat 15(1):7–12

    Article  Google Scholar 

  19. Farrington SM, Dunlop MG (1999) Mosaicism and sporadic familial adenomatous polyposis. Am J Hum Genet 64(2):653–658 Feb

    Article  PubMed  CAS  Google Scholar 

  20. Aretz S, Stienen D, Friedrichs N et al (2007) Somatic APC mosaicism: a frequent cause of familial adenomatous polyposis (FAP). Hum Mutat 28(10):985–992

    Article  PubMed  CAS  Google Scholar 

  21. Hes FJ, Nielsen M, Bik EC, et al (2007) Somatic APC Mosaicism: An Underestimated Cause Of Polyposis Coli. Gut (in press)

  22. Bisgaard ML, Fenger K, Bulow S, Niebuhr E, Mohr J (1994) Familial adenomatous polyposis (FAP): frequency, penetrance, and mutation rate. Hum Mutat 3(2):121–125

    Article  PubMed  CAS  Google Scholar 

  23. Aretz S, Uhlhaas S, Caspari R et al (2004) Frequency and parental origin of de novo APC mutations in familial adenomatous polyposis. Eur J Hum Genet 12(1):52–58 Jan

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We greatly appreciate the diagnostic skills and far-reaching intuition of Dr. Mark Peterson D.D.S, who first recognized osteomas and cysts in the family and referred them for further medical attention. We also acknowledge Jared Cox for family history data evaluation and pedigree construction. This research is supported by NCI grants P01-CA073992 (RWB) and R01-CA040641(RWB).

Author information

Authors and Affiliations

  1. Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Room 3146, Salt Lake City, UT, 84112-5550, USA

    Angela L. Schwab, Thérèse M. F. Tuohy, Michelle Condie & Deborah W. Neklason

  2. Department of Oncological Sciences, University of Utah, Salt Lake City, UT, USA

    Deborah W. Neklason & Randall W. Burt

  3. Department of Medicine, University of Utah, Salt Lake City, UT, USA

    Randall W. Burt

Authors
  1. Angela L. Schwab
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thérèse M. F. Tuohy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michelle Condie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Deborah W. Neklason
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Randall W. Burt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thérèse M. F. Tuohy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schwab, A.L., Tuohy, T.M.F., Condie, M. et al. Gonadal mosaicism and familial adenomatous polyposis. Familial Cancer 7, 173–177 (2008). https://doi.org/10.1007/s10689-007-9169-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10689-007-9169-1

Keywords

Search

Navigation