Two Chinese pedigrees for adenomatous polyposis coli: new mutations at codon 1309 and predisposition to phenotypic variations.

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease caused by a mutation in the adenomatous polyposis coli (APC) gene. Some studies have attempted to correlate mutations at codon 1309 with classic FAP (≥100 colorectal polyps). We report two Chinese FAP pedigrees with new frameshift mutations at codon 1309, in which affected individuals manifest phenotypic variations. Comprehensive physical examinations were performed for all living individuals and the medical data of deceased patients were collected. Screening of the APC and human mutY homolog (MUTYH) genes for germline mutations was conducted by direct polymerase chain reaction (PCR) sequencing. In two pedigrees, a heterozygous deletion in exon 16 of the APC gene was present in all FAP patients but absent in the unaffected individuals. There were no changes to the MUTYH gene. The first pedigree, with a new frameshift mutation at c.3926_3930 del AAAAG (p. Glu1309Aspfs X4), exhibited obvious differences in the polyp number such that the proband manifested only three colorectal polyps, whereas another patients showed the symptoms of classic FAP. The second pedigree, also traced a new mutation at c.3922_3925 del AAAG (p. Glu1309Argfs X11). Although all of the patients presented with classic polyposis, one of them exhibited a delayed onset of colorectal cancer in his 50s. Two novel mutations at codon 1309 in two Chinese families suffering from FAP could enrich the germline mutation spectrum of the APC gene. Families of individuals might manifest different phenotypes, even with an identical codon 1309 mutation, unlike in previous studies.