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

Correlations between mutation site in APC and phenotype of familial adenomatous polyposis (FAP): A review of the literature

“…The third region which is associated with AFAP is the alternatively spliced site of exon 9 (codon 312-412) [13,23,27,30,32,[36][37][38]. Despite the consistent relation between this exon 9 mutation and mild disease, intrafamilial phenotypic variability has been reported [36,38].…”

A novel indel in exon 9 of APC upregulates a ‘skip exon 9’ isoform and causes very severe familial adenomatous polyposis

“…Moreover, the patient had relative sparing of polyps in the proximal colon, a feature in contrast to most mutations at the 5 0 end of exon 9 that typically results in aFAP. 5,8,12 The six synchronous tumors were also predominantly on the left (two transverse, two sigmoid, and two rectal). The exon 8-10 connection reminded us of our previous unpublished finding of a 'skip exon 9' isoform that is present in low abundance in the lymphocytes of all 22 FAP patients and 21 healthy individuals screened with an age range of 14-70 years.…”

A Splice-Site Mutation in Exon 4 of the APC Gene in a Family with Attenuated Familial Adenomatous Polyposis

“…3). The mutations in the APC gene associated with AFAP have mainly been located in three regions of the gene: the extreme 5 end (exons 1-5), the 3 end and the alternatively spliced region of exon 9 [5][6][7][8]. Mutations at the 5 end end of the gene have been reported most frequently.…”