title: Germline mutations in the 3' part of APC exon 15 do not result in truncated proteins and are associated with attenuated adenomatous polyposis coli.
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.
authors.affiliation: MGC-Department of Human Genetics, Sylvius Laboratory, Faculty of Medicine, Leiden University, The Netherlands. rob@ruly46.medfac.leidenuniv.nl
authors.forename: R B
authors.initials: RB
authors.lastname: van der Luijt
authors.forename: P
authors.initials: P
authors.lastname: Meera Khan
authors.forename: H F
authors.initials: HF
authors.lastname: Vasen
authors.forename: C
authors.initials: C
authors.lastname: Breukel
authors.forename: C M
authors.initials: CM
authors.lastname: Tops
authors.forename: R J
authors.initials: RJ
authors.lastname: Scott
authors.forename: R
authors.initials: R
authors.lastname: Fodde
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype