BACKGROUND: The patient with 10 or more adenomas in the colon poses a diagnostic 
challenge. Beside germline mutations in the APC and MUTYH genes, only four cases 
of mosaic APC mutations have been reported.
AIM: Given the relatively high frequency of de novo APC mutations in familial 
adenomatous polyposis (FAP), an investigation was carried out into whether the 
proportion of somatic mosaic APC mutations is currently underestimated.
METHODS: Between 1 January 1994 and 31 December 2005 germline mutation analysis 
was performed in 599 consecutive index patients with polyposis coli referred for 
diagnostic APC scanning using a combination of denaturing gradient gel 
electrophoresis (DGGE) and protein truncation test (PTT). Variants were analysed 
by direct sequencing with primers flanking those used for DGGE and PTT, and 
quantified using pyrosequencing.
RESULTS: Scrutinizing the molecular genetic results and family data of 242 index 
patients with pathogenic APC mutations led to the identification of 10 mosaic 
cases (4%). C>T transitions were observed in CGA sites in four of the 10 cases 
with somatic mosaicism, which is significantly more than 26 of the 232 
non-mosaic cases (p = 0.02). Phenotypes of patients with somatic mosaicism 
ranged from an attenuated form of polyposis coli to florid polyposis with major 
extracolonic manifestations.
CONCLUSIONS: Mosaicism occurs in a significant number of APC mutations and it is 
estimated that one-fifth of the de novo cases of FAP are mosaic. Clinically, the 
severity of manifestations in offspring and the recurrence risk for siblings of 
apparently sporadic polyposis patients may be underestimated due to parental APC 
mosaicism.