Details

Autor(en) / Beteiligte

• Sieber, O. M.
• Lamlum, H.
• Crabtree, M.D.
• Rowan, A. J.
• Barclay, E.
• Lipton, L.
• Hodgson, S.
• Thomas, H. J. W.
• Neale, K.
• Phillips, R. K. S.
• Farrington, S. M.
• Dunlop, M. G.
• Mueller, H. J.
• Bisgaard, M. L.
• Bulow, S.
• Fidalgo, P.
• Albuquerque, C.
• Scarano, M. I.
• Bodmer, W.
• Tomlinson, I. P. M.
• Heinimann, K.

Titel

Whole-Gene APC Deletions Cause Classical Familial Adenomatous Polyposis, but not Attenuated Polyposis or "Multiple" Colorectal Adenomas

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2002-03, Vol.99 (5), p.2954-2958

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2002

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Familial adenomatous polyposis (FAP) is a dominantly inherited colorectal tumor predisposition that results from germ-line mutations in the APC gene (chromosome 5q21). FAP shows substantial phenotypic variability: classical polyposis patients develop more than 100 colorectal adenomas, whereas those with attenuated polyposis (AAPC) have fewer than 100 adenomas. A further group of individuals, so-called "multiple" adenoma patients, have a phenotype like AAPC, with 3-99 polyps throughout the colorectum, but mostly have no demonstrable germ-line APC mutation. Routine mutation detection techniques fail to detect a pathogenic APC germ-line mutation in approximately 30% of patients with classical polyposis and 90% of those with AAPC/multiple adenomas. We have developed a real-time quantitative multiplex PCR assay to detect APC exon 14 deletions. When this technique was applied to a set of 60 classical polyposis and 143 AAPC/multiple adenoma patients with no apparent APC germ-line mutation, deletions were found exclusively in individuals with classical polyposis (7 of 60, 12%). Fine-mapping of the region suggested that the majority (6 of 7) of these deletions encompassed the entire APC locus, confirming that haploinsufficiency can result in a classical polyposis phenotype. Screening for germ-line deletions in APC mutation-negative individuals with classical polyposis seems warranted.