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APC promoter 1B deletion in seven American families with familial adenomatous polyposis
Author(s) -
Snow A.K.,
Tuohy T.M.F.,
Sargent N.R.,
Smith L.J.,
Burt R.W.,
Neklason D.W.
Publication year - 2015
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12503
Subject(s) - familial adenomatous polyposis , adenomatous polyposis coli , biology , genetics , multiplex ligation dependent probe amplification , proband , allele , haplotype , locus (genetics) , microbiology and biotechnology , gene , mutation , colorectal cancer , cancer research , cancer , exon
Familial adenomatous polyposis ( FAP ) is a colorectal cancer predisposition syndrome caused by mutations in the adenomatous polyposis coli ( APC ) 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 APC promoter 1B , seven probands were identified with a deletion of promoter 1B . Using haplotype analysis spanning the APC 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 APC 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 APC promoter deletions as a cause of FAP and identifies a founder mutation in FAP patients from the United States.