title: The identical 5' splice-site acceptor mutation in five attenuated APC families from Newfoundland demonstrates a founder effect.
abstract: Inherited mutations of the APC gene predispose carriers to multiple adenomatous polyps of the colon and rectum and to colorectal cancer. Mutations located at the extreme 5' end of the APC gene, however, are associated with a less severe disease known as attenuated adenomatous polyposis coli (AAPC). Many individuals with AAPC develop relatively few colorectal polyps but are still at high risk for colorectal cancer. We report here the identification of a 5' APC germline mutation in five separately ascertained AAPC families from Newfoundland, Canada. This disease-causing mutation is a single basepair change (G to A) in the splice-acceptor region of APC intron 3 that creates a mutant RNA without exon 4 of APC. The observation of the same APC mutation in five families from the same geographic area demonstrates a founder effect. Furthermore, the identification of this germline mutation strengthens the correlation between the 5' location of an APC disease-causing mutation and the attenuated polyposis phenotype.
authors.affiliation: University of Utah, Department of Oncological Sciences, Salt Lake City 84112-5330, USA.
authors.forename: L
authors.initials: L
authors.lastname: Spirio
authors.forename: J
authors.initials: J
authors.lastname: Green
authors.forename: J
authors.initials: J
authors.lastname: Robertson
authors.forename: M
authors.initials: M
authors.lastname: Robertson
authors.forename: B
authors.initials: B
authors.lastname: Otterud
authors.forename: J
authors.initials: J
authors.lastname: Sheldon
authors.forename: E
authors.initials: E
authors.lastname: Howse
authors.forename: R
authors.initials: R
authors.lastname: Green
authors.forename: J
authors.initials: J
authors.lastname: Groden
authors.forename: R
authors.initials: R
authors.lastname: White
authors.forename: M
authors.initials: M
authors.lastname: Leppert
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000328:Adult; D000368:Aged; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004641:Emigration and Immigration; D005091:Exons; D005260:Female; D018703:Founder Effect; D017491:Genes, APC; D018095:Germ-Line Mutation; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D009523:Newfoundland and Labrador; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D012326:RNA Splicing / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D004247:DNA