welcome to oneFAPvoice

- a positively charged Familial Adenomatous Polyposis community.
  • join today!
scientific articles

APC Germline Mutations in Individuals Being Evaluated for Familial Adenomatous Polyposis: A Review of the Mayo Clinic Experience With 1591 Consecutive Tests

key information

source: The Journal of molecular diagnostics

year: 2013

authors: Kerr S E, Thomas C B, Thibodeau S N, Ferber M J, Halling K C

summary/abstract:

Inactivating APC mutations cause familial adenomatous polyposis, classically characterized by hundreds to thousands of adenomatous colorectal polyps and cancer. Historically, 98% of pathogenic alterations in APC are nonsense or frameshift mutations; however, few reported series have used techniques that test for large deletions or duplications. Splice site mutations are only rarely documented. Consecutive cases (n = 1591) submitted for complete APC gene analysis during a 4-year period were reviewed. Testing included mutation screening (Sanger sequencing or conformation sensitive gel electrophoresis and protein truncation testing) with reflex confirmation sequencing. Gene deletion or duplication analysis was performed in 1421 cases by multiplex ligation-dependent probe amplification. Testing yielded 411 pathogenic, 20 likely pathogenic, 15 variant of uncertain significance, 140 likely benign, and 1005 negative reports. Identified were 168 novel variants (103 pathogenic, 5 likely pathogenic, 12 variant of uncertain significance, and 48 likely benign). Of the 431 pathogenic or likely pathogenic mutations, frameshift, nonsense, splice site, and large deletion or duplication mutations represented 43%, 42%, 9%, and 6% of cases, respectively. This is the largest report of clinical APC testing experience with concurrent multiplex ligation-dependent probe amplification. In addition to nonsense and frameshift mutations, large deletions or duplications and canonical splice site mutations are a significant cause of familial adenomatous polyposis. Despite technological advances, broad allelic, locus, and phenotypic heterogeneity continue to pose challenges for genetic testing of patients with colorectal adenomatous polyposis.

organization: Mayo Clinic

DOI: 10.1016/j.jmoldx.2012.07.005

read more full text source

To improve your experience on this site, we use cookies. This includes cookies essential for the basic functioning of our website, cookies for analytics purposes, and cookies enabling us to personalize site content. By clicking on 'Accept' or any content on this site, you agree that cookies can be placed. You may adjust your browser's cookie settings to suit your preferences.
More information

The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.

Close