APC promoter 1B deletion in seven American families with familial adenomatous polyposis. (14th October 2014)

• Record Type: Journal Article
• Authors: Snow, A.K.; Tuohy, T.M.F.; Sargent, N.R.; Smith, L.J.; Burt, R.W.; Neklason, D.W.
• Is Part Of: Clinical genetics. Volume 88:Number 4(2015:Oct.)
• Page Start: 360
• Page End: 365
• Publication Date: 2014-10-14
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12503
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main" id="cge12503-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p id="cge12503-para-0001">Familial adenomatous polyposis (FAP) is a colorectal cancer predisposition syndrome caused by mutations in the adenomatous polyposis coli (<italic>APC</italic>) gene. Clinical genetic testing fails to identify disease causing mutations in up to 20% of clinically apparent FAP cases. Following the inclusion of multiplex ligation‐dependent probe amplification (MLPA) probes specific for <italic>APC</italic> promoter 1B, seven probands were identified with a deletion of promoter 1B. Using haplotype analysis spanning the <italic>APC</italic> locus, the seven families appear to be identical by descent from a common founder. The clinical phenotype of 19 mutation carriers is classical FAP with colectomy at an average age of 24. The majority of cases had a large number of duodenal and gastric polyps. Measurements of allele‐specific expression of <italic>APC</italic> mRNA using TaqMan assay confirmed that relative expression in the allele containing the promoter 1B deletion was reduced 42–98%, depending on tissue type. This study confirms the importance of <italic>APC</italic> promoter deletions as a cause of FAP and identifies a founder mutation in FAP patients from the United States.</p> </abstract>