{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:22:51Z","timestamp":1790400171152,"version":"4.1.0"},"reference-count":21,"publisher":"BMJ","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2011,5,5]]},"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited colorectal cancer predisposition caused by germ line mutations in the <jats:italic>APC<\/jats:italic> (adenomatous polyposis coli) gene. Current recommendations for <jats:italic>APC<\/jats:italic> mutation analysis advise full gene sequencing to identify point mutations and small insertions\/deletions as well as the multiplex ligation dependent probe amplification (MLPA) technique to detect gene dosage alterations. Use of the protein truncation test (PTT) as a pre-screening tool has thus been largely replaced with direct end-to-end sequencing, mainly because of its limited sensitivity and failure to identify <jats:italic>APC<\/jats:italic> missense alterations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>This report describes two unrelated patients with classical polyposis coli and unremarkable family history in whom neither full sequencing nor MLPA on leucocyte derived DNA could identify a pathogenic <jats:italic>APC<\/jats:italic> mutation. Applying the PTT, however, provided evidence of aberrant bands in both patients. Subsequent targeted mutation analysis of their tumour derived DNA allowed the identification of two novel, pathogenic <jats:italic>APC<\/jats:italic> alterations present in a mosaic state, at blood levels (1\u201315%) below the detection limits of conventional Sanger sequencing.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title> \n                  <jats:p>The findings demonstrate the value of the PTT in identifying mosaic mutations in apparently <jats:italic>APC<\/jats:italic> mutation negative FAP patients with de novo classical polyposis and the need to keep the PTT within the diagnostic repertoire for <jats:italic>APC<\/jats:italic> mutation analysis.<\/jats:p>\n               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