Linked Life Data

17486639

Source:http://linkedlifedata.com/resource/pubmed/id/17486639

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2007-9-13
pubmed:abstractText
Somatic mutational mosaicism presents a challenge for both molecular and clinical diagnostics and may contribute to deviations from predicted genotype-phenotype correlations. During APC mutation screening in 1,248 unrelated patients with familial adenomatous polyposis (FAP), we identified 75 cases with an assumed or confirmed de novo mutation. Prescreening methods (protein truncation test [PTT], DHPLC) indicated the presence of somatic mosaicism in eight cases (11%). Sequencing of the corresponding fragments revealed very weak mutation signals, pointing to the presence of either nonsense or frameshift mutations at low level. All mutations were confirmed and quantified by SNaPshot analysis: in leukocyte DNA from the eight patients, the percentage of mosaicism varied between 5.5% and 77%, while the proportion of the mutation in DNA extracted from adenomas of the respective patient was consistently higher. The eight mutations identified as mosaic are localized within codons 216-1464 of the APC gene. According to the known genotype-phenotype correlation, patients with mutations in this region exhibit typical or severe FAP. However, six of the eight patients presented with an attenuated or atypical polyposis phenotype. Our data demonstrate that in a fraction of FAP patients the causative APC mutation may not be detected due to weak signals or somatic mosaicism that is restricted to tissues other than blood. SNaPshot analysis was proven to be an easy, rapid, and reliable method of confirming low-level mutations and evaluating the degree of mosaicism. Some of the deviations from the expected phenotype in FAP can be explained by the presence of somatic mosaicism.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1098-1004
pubmed:author
pubmed:copyrightInfo
Copyright 2007 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
985-92
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Somatic APC mosaicism: a frequent cause of familial adenomatous polyposis (FAP).
pubmed:affiliation
Institute of Human Genetics, University Hospital of Bonn, Bonn, Germany. Stefan.Aretz@ukb.uni-bonn.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't