Detection of APC germ line mosaicism in patients with de novo familial adenomatous polyposis: a plea for the PTT

Current recommendations for APC mutation analysis in patients with familial adenomatous polyposis (FAP) advise full gene sequencing and gene dosage analysis replacing the protein truncation test (PTT) as a pre-screening tool. Here we report on two unrelated patients with classical FAP and unremarkable family history in whose leukocyte-derived DNA no pathogenic APC mutations could be identified. PTT analysis, however, evidenced aberrant bands in both patients with subsequent targeted mutation analysis of their tumour-derived DNA identifying two novel, pathogenic APC alterations present in a mosaic state, at blood levels (1 – 15%) below the detection limits of conventional Sanger sequencing. Our findings demonstrate the value of the PTT to identify mosaic mutations in apparently APC mutation-negative FAP patients with de novo classical polyposis and the need to keep the PTT within the diagnostic repertoire for APC mutation analysis. (By Karl Heinimann, http://jmg.bmj.com/content/early/2011/06/07/jmg.2011.089474.abstract?papetoc )