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Human Genetics

, Volume 98, Issue 6, pp 727–734 | Cite as

Germline mutations in the 3′ part of APC exon 15 do not result in truncated proteins and are associated with attenuated adenomatous polyposis coli

  • R. B. van der Luijt
  • P. Meera Khan
  • Hans F. A. Vasen
  • C. Breukel
  • Carli M. J. Tops
  • Rodney J. Scott
  • Riccardo Fodde
Original investigation

Abstract

Familial adenomatous polyposis (FAP) is an inherited predisposition to colorectal cancer characterized by the development of numerous adenomatous polyps predominantly in the colorectal region. Germline mutations in the adenomatous polyposis coli (APC) gene are responsible for most cases of FAP. Mutations at the 5′ end of APC are known to be associated with a relatively mild form of the disease, called attenuated adenomatous polyposis coli (AAPC). We identified a frameshift mutation in the 3′ part of exon 15, resulting in a stop codon at 1862, in a large Dutch kindred with AAPC. Western blot analysis of lymphoblastoid cell lines derived from affected family members from this kindred, as well as from a previously reported Swiss family carrying a frameshift mutation at codon 1987 and displaying a similar attenuated phenotype, showed only the wild-type APC protein. Our study indicates that chain-terminating mutations located in the 3′ part of APC do not result in detectable truncated polypeptides and we hypothesize that this is likely to be the basis for the observed AAPC phenotype.

Keywords

Codon Colorectal Cancer Stop Codon Germline Mutation Familial Adenomatous Polyposis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • R. B. van der Luijt
    • 1
  • P. Meera Khan
    • 1
  • Hans F. A. Vasen
    • 2
  • C. Breukel
    • 1
  • Carli M. J. Tops
    • 1
  • Rodney J. Scott
    • 3
  • Riccardo Fodde
    • 1
  1. 1.MGC-Department of Human Genetics, Sylvius Laboratory, Faculty of Medicine, Leiden University, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands Tel.: +31-71-5276090; Fax: +31-71-5276075; e-mail: rob@ruly46.medfac.leidenuniv.nl; meera@ruly46.medfac.leidenuniv.nlNL
  2. 2.Foundation for the Detection of Hereditary Tumours, Leiden, The NetherlandsNL
  3. 3.Humangenetik, Department of Forschung, Kantonsspital Basle, Basle, SwitzerlandCH

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