title: A family with attenuated familial adenomatous polyposis due to a mutation in the alternatively spliced region of APC exon 9.
abstract: A family is presented with attenuated familial adenomatous polyposis of variable phenotype. The clinical features range from sparse right-sided polyposis and cancer in the proximal colon at the age of 34 to pan-colonic polyposis and cancer at the age of 68. Rectal sparing is common to all affected members. Heteroduplex analysis detected bands of altered mobility in exon 9 of the APC gene in all affected family members. Subsequently, a frameshift mutation was found in the alternatively spliced region of exon 9 at codon 398 which resulted in a stop signal 4 codons downstream. Alternatively spliced transcripts that delete the mutation were readily amplified from normal colonic mucosa and therefore create a mechanism for the attenuated phenotype seen in this family.
authors.affiliation: Glaxo Conjoint Gastroenterology Laboratory, Royal Brisbane Hospital Foundation Clinical Research Centre, Australia. joanneY@qimr.edu.au
authors.forename: J
authors.initials: J
authors.lastname: Young
authors.forename: L A
authors.initials: LA
authors.lastname: Simms
authors.forename: J
authors.initials: J
authors.lastname: Tarish
authors.forename: R
authors.initials: R
authors.lastname: Buttenshaw
authors.forename: N
authors.initials: N
authors.lastname: Knight
authors.forename: G J
authors.initials: GJ
authors.lastname: Anderson
authors.forename: A
authors.initials: A
authors.lastname: Bell
authors.forename: B
authors.initials: B
authors.lastname: Leggett
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D018076:DNA, Complementary; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009692:Nucleic Acid Heteroduplexes; D010375:Pedigree; D010641:Phenotype
chemical_list: D018076:DNA, Complementary; D009692:Nucleic Acid Heteroduplexes