Background: More than 100 different mutations in the adenomatous polyposis coli (APC) gene have been identified; virtually all lead to the production of a truncated protein. Clinical details of patients with missense mutations undoubtedly cosegregating with the disease have not been reported and may be relevant in understanding the APC protein function.
Methods: In one family with familial adenomatous polyposis (FAP) the APC gene was analyzed by SSCP and sequencing of the aberrant SSCP band.
Results: A missense mutation in exon 15 at nucleotide 4921 segregating with the disease was observed. This predicts a tryptophan instead of an arginine at amino acid 1641 of the APC protein. No such mutation was present in 100 control subjects.
Conclusions: In this family the colonic manifestations are as expected for classical FAP. However, the occurrence of congenital hypertrophy of the retinal pigment epithelium is unusual, owing to the inconsistency of this manifestation between family members and because congenital hypertrophy of the retinal pigment epithelium is generally absent when mutations are after codon 1387.