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 o f variable phenotype. The clinical features range from sparse right-si ded 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 comm on to all affected members. Heteroduplex analysis detected bands of al tered mobility in exon 9 of the APC gene in all affected family member s. 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 theref ore create a mechanism for the attenuated phenotype seen in this famil y. (C) 1998 Wiley-Liss, Inc.