Phenotypic expression in familial adenomatous polyposis: partial prediction by mutation analysis

The phenotypic expression in familial adenomatous polyposis (FAP) is variable. This study compares the phenotype of 27 patients with an identical 5 base pair (bp) deletion at codon 1309 with a group of 61 matched patients with FAP where knowledge of specific mutations is not available and with seven other different mutations in 24 subjects. Patients with the codon 1309 deletion have significantly more colorectal polyps at the time of colectomy than age and sex matched FAP controls (p = 0.0001). The median number of polyps in colectomy specimens of patients with the deletion at codon 1309 was 4000 (interquartile (IQ) range 3000-4875), compared with 600 (IQ range 488-1400) in the matched controls. Mutations at codon 1323, 1407, and 233 were also associated with large numbers of polyps. Desmoid disease and extracolonic cancers were more common with the mutation at codon 1309 (p = 0.003). In conclusion, there may be a correlation between a specific germline mutation and the number of large bowel polyps. There is residual heterogeneity in phenotypic expression, however, and this may result from the influence of other genes, specific environmental factors or chance.