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Submicroscopic deletions of the APC gene: a frequent cause of familial adenomatous polyposis that may be overlooked by conventional mutation scanning
  1. *Yorkshire Regional DNA Laboratory, Department of Clinical Genetics, Ashley Wing, St James's University Teaching Hospital, Beckett Street, Leeds LS9 7TF, UK
  2. †Department of Clinical Genetics, St James's University Teaching Hospital, Leeds, UK
  1. Dr Taylor, gtaylor{at}

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Editor—Familial adenomatous polyposis (FAP) is an autosomal dominant colon cancer predisposition syndrome in which patients develop hundreds to thousands of precancerous colonic polyps that have a high risk of becoming malignant.

Despite the fact that deletions of the APClocus were originally used to map1 2 and identify3 4 the APC gene, most studies of mutations in APC have used techniques which would not detect deletions.5-7 Molecular analysis of the APC gene in FAP patients has found the pathogenic mutation in 70% of cases,8 but a substantial minority have no mutation identified.

Interstitial deletions of chromosome 5q, which include theAPC locus, have been reported in patients with polyposis coli and mental retardation.9Submicroscopic deletions have been reported in only a few cases.10 11 In one family,10 linkage analysis with flanking and intragenic markers followed by in situ hybridisation with intragenic cosmid clones showed that the deletion was approximately 200 kb and included more than the 3′ half of theAPC gene and the 3′ adjacent D5S346 microsatellite. A recent report11 described a quantitative PCR assay to detect submicroscopic deletions which included the entireAPC gene and the adjacent D5S346 microsatellite in three unrelated Italian FAP families. These submicroscopic deletions do not appear to be associated with mental retardation.

Microsatellite analysis of families with FAP in our region showed one family with apparent non-maternity at D5S346 in one of the affected offspring of an affected mother, suggesting the possibility of anAPC deletion. A quantitative PCR assay was therefore developed to detect submicroscopic deletions of theAPC gene.

Previous analysis of 68 FAP families from the Yorkshire region found the pathogenic mutation in 46 cases (67%). These cases were referred for testing (with informed consent) from the Yorkshire Regional Clinical …

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