{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T17:50:28Z","timestamp":1774115428731,"version":"3.50.1"},"reference-count":28,"publisher":"Proceedings of the National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,3,5]]},"abstract":"<jats:p>\n            Familial adenomatous polyposis (FAP) is a dominantly inherited colorectal tumor predisposition that results from germ-line mutations in the\n            <jats:italic>APC<\/jats:italic>\n            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 \u201cmultiple\u201d adenoma patients, have a phenotype like AAPC, with 3\u201399 polyps throughout the colorectum, but mostly have no demonstrable germ-line\n            <jats:italic>APC<\/jats:italic>\n            mutation. Routine mutation detection techniques fail to detect a pathogenic\n            <jats:italic>APC<\/jats:italic>\n            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\n            <jats:italic>APC<\/jats:italic>\n            exon 14 deletions. When this technique was applied to a set of 60 classical polyposis and 143 AAPC\/multiple adenoma patients with no apparent\n            <jats:italic>APC<\/jats:italic>\n            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\n            <jats:italic>APC<\/jats:italic>\n            locus, confirming that haploinsufficiency can result in a classical polyposis phenotype. Screening for germ-line deletions in\n            <jats:italic>APC<\/jats:italic>\n            mutation-negative individuals with classical polyposis seems warranted.\n          <\/jats:p>","DOI":"10.1073\/pnas.042699199","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:37:36Z","timestamp":1027694256000},"page":"2954-2958","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":105,"title":["Whole-gene\n            <i>APC<\/i>\n            deletions cause classical familial adenomatous polyposis, but not attenuated polyposis or \u201cmultiple\u201d colorectal adenomas"],"prefix":"10.1073","volume":"99","author":[{"given":"O. M.","family":"Sieber","sequence":"first","affiliation":[{"name":"Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom; Imperial Cancer Research Fund Colorectal Unit and Polyposis Registry, St. Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, United Kingdom; Department of Clinical Genetics, Guy's Hospital, London SE1 9RT, United Kingdom; University of Edinburgh and Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United..."}]},{"given":"H.","family":"Lamlum","sequence":"additional","affiliation":[{"name":"Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom; Imperial Cancer Research Fund Colorectal Unit and Polyposis Registry, St. Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, United Kingdom; Department of Clinical Genetics, Guy's Hospital, London SE1 9RT, United Kingdom; University of Edinburgh and Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United..."}]},{"given":"M. D.","family":"Crabtree","sequence":"additional","affiliation":[{"name":"Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom; Imperial Cancer Research Fund Colorectal Unit and Polyposis Registry, St. Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, United Kingdom; Department of Clinical Genetics, Guy's Hospital, London SE1 9RT, United Kingdom; University of Edinburgh and Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United..."}]},{"given":"A. J.","family":"Rowan","sequence":"additional","affiliation":[{"name":"Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom; Imperial Cancer Research Fund Colorectal Unit and Polyposis Registry, St. Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, United Kingdom; Department of Clinical Genetics, Guy's Hospital, London SE1 9RT, United Kingdom; University of Edinburgh and Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United..."}]},{"given":"E.","family":"Barclay","sequence":"additional","affiliation":[{"name":"Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom; Imperial Cancer Research Fund Colorectal Unit and Polyposis Registry, St. Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, United Kingdom; Department of Clinical Genetics, Guy's Hospital, London SE1 9RT, United Kingdom; University of Edinburgh and Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United..."}]},{"given":"L.","family":"Lipton","sequence":"additional","affiliation":[{"name":"Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom; Imperial Cancer Research Fund Colorectal Unit and Polyposis Registry, St. Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, United Kingdom; Department of Clinical Genetics, Guy's Hospital, London SE1 9RT, United Kingdom; University of Edinburgh and Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United..."}]},{"given":"S.","family":"Hodgson","sequence":"additional","affiliation":[{"name":"Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom; Imperial Cancer Research Fund Colorectal Unit and Polyposis Registry, St. Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, United Kingdom; Department of Clinical Genetics, Guy's Hospital, London SE1 9RT, United Kingdom; University of Edinburgh and Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United..."}]},{"given":"H. J. W.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom; Imperial Cancer Research Fund Colorectal Unit and Polyposis Registry, St. Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, United Kingdom; Department of Clinical Genetics, Guy's Hospital, London SE1 9RT, United Kingdom; University of Edinburgh and Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United..."}]},{"given":"K.","family":"Neale","sequence":"additional","affiliation":[{"name":"Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom; Imperial Cancer Research Fund Colorectal Unit and Polyposis Registry, St. Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, United Kingdom; Department of Clinical Genetics, Guy's Hospital, London SE1 9RT, United Kingdom; University of Edinburgh and Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United..."}]},{"given":"R. K. S.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom; Imperial Cancer Research Fund Colorectal Unit and Polyposis Registry, St. Mark's Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, United Kingdom; Department of Clinical Genetics, Guy's Hospital, London SE1 9RT, United Kingdom; University of Edinburgh and Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United..."}]},{"given":"S. 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