Peer-review started: September 22, 2017
First decision: October 30, 2017
Revised: November 21, 2017
Accepted: December 29, 2017
Article in press: December 29, 2017
Published online: February 27, 2018
Processing time: 140 Days and 7 Hours
We present a patient with a history of colonic polyposis and family history significant for colon polyps and colorectal cancer (CRC). The patient and the family also had a history of bone loss of the jaw and early tooth loss, consistent with oligodontia. Genetic testing revealed the patient to have a previously unpublished variant of unknown significance (VUS) in the AXIN2 gene. These clinical findings have been demonstrated previously in only two other families, both of which exhibited oligodontia, colorectal neoplasia (polyps and cancer) and a heterozygous mutation in AXIN2. The AXIN2 protein is component of the Wnt pathway, which is known to be vital for organism development and cellular homeostasis. Alterations of the Wnt pathway lead to cell proliferation and neoplasm, in addition to agenesis of physical structures (such as teeth). The analysis of our pedigree further supports an association between colonic neoplasm (polyposis and CRC), the AXIN2 gene in general, and this particular VUS. It also highlights the importance of analyzing and disseminating information on pedigrees with less commonly encountered genomic abnormalities so that genotypic-phenotypic correlations can be solidified.
Core tip: Biochemical research, murine models, and 2 prior human families lend support to a genotypic-phenotypic correlation between alterations in the AXIN2 and polyposis/colorectal cancer. Our paper uses genetic testing and pedigree analysis to include a third family. This information would impact future genetic testing, the classification of identified variants, and screening in those with identified AXIN2 mutations and variants.