APC Somatic Mosaicism in a Patient with Gardner Syndrome Carrying the E1573X Mutation: Report of a Case

We report a case of somatic APC mosaicism in an person with a clinical diagnosis of Gardner syndrome with features of attenuated polyposis coli and with an uninformative family history. In initial screening for APC mutations, the germline mutation E1573X was detected in a lower proportion than that predicted by a heterozygous mutation indicating the presence of somatic mosaicism. Pyrosequencing confirmed this hypothesis and quantified the presence of the mutation in approximately 18% of the blood lymphocytes. Mutational analysis performed in the offspring revealed a fully heterozygous E1573X mutation in 2 of the 3 individuals tested. The milder colonic phenotype exhibited by the index patient could be a consequence of the presence of the mosaicism in the colon mucosa. The detection of the mutation in other tissues and in the offspring suggests that it may have occurred early during embryogenesis, before the separation of the embryonic layers. The E1573X mutation is the most distal mutation in the APC sequence reported to date as a mosaic and, interestingly, in the context of Gardner syndrome with extensive extracolonic features. Mosaicism is an important consequence of de novo APC mutations and it should be considered in the management of apparently sporadic or de novo cases, particularly in the evaluation of the risk of siblings and offspring.