NOVEL GERMLINE APC GENE MUTATION IN A LARGE FAMILIAL ADENOMATOUS POLYPOSIS KINDRED DISPLAYING VARIABLE PHENOTYPES

The APC gene is mutated in the germline of people from families where there is a predisposition to develop polyposis coli. Many mutations ha ve been described but the relation between their site and the phenotyp ic expression of the disease remains unclear. The most commonly seen m utation occurs at codon 1309. Many other mutations have been described towards the 5' end of exon 15 of the APC gene but comparatively few h ave been seen towards the 3' end. Recent reports have indicated the po ssibility of a functional boundary with respect to severity and age of onset of disease, which lies towards the 5' end of the gene. This rep ort describes a large family whose affected members present with a ver y variable phenotype ranging from an early onset and severe form to a comparatively mild later onset one. The mutation that predisposes to d isease in this family is at a previously undescribed site that lies to wards the 3' end of exon 15 of the APC gene, which results in a stop c odon. Interestingly, the stop codon is 63 codons downstream of the mut ation and therefore may affect the expression of the disease. The addi tion of this mutation to the growing list of mutations described in th e APC gene may provide some insight into the genotype/phenotype relati on of the disease thus contributing to the understanding and significa nce of mutations at specific sites in the APC gene.