A family with attenuated familial adenomatous polyposis due to a mutation in the alternatively spliced region of APC exon 9

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. Hum Mutat 11:450–455, 1998. © 1998 Wiley‐Liss, Inc.