Case Report
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Med Genet. Feb 27, 2018; 8(1): 1-4
Published online Feb 27, 2018. doi: 10.5496/wjmg.v8.i1.1
Pedigree analysis supports a correlation between an AXIN2 variant and polyposis/colorectal cancer
Amrit Lamba, Parth Parekh, Chris T Dvorak, Jordan J Karlitz
Amrit Lamba, Department of Internal Medicine, Tulane University, New Orleans, LA 70112, United States
Parth Parekh, Department of Gastroenterology, Carillion Clinic, Roanoke, VA 24016, United States
Chris T Dvorak, Department of Genetics, Tulane University, New Orleans, LA 70112, United States
Jordan J Karlitz, Department of Gastroenterology, Tulane University, New Orleans, LA 70112, United States
Author contributions: Lamba A drafted the manuscript; Lamba A, Parekh P and Karlitz JJ acquired the data; Lamba A, Parekh P, Dvorak CT and Karlitz JJ critically revised the manuscript; Karlitz JJ created the study concept and is the article guarantor.
Informed consent statement: The patient involved in this study gave her written informed consent authorizing use and disclosure of her protected health information.
Conflict-of-interest statement: All the authors have no conflicts of interests to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Parth Parekh, MD, Academic Fellow, Department of Gastroenterology, Carillion Clinic, 1906 Belleview Ave, Roanoke, VA 24016, United States.
Telephone: +1-845-5513357
Received: September 8, 2017
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

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 Genetic testing revealed the patient to have a previously unpublished variant of unknown significance (VUS) in the AXIN2 gene.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.

Keywords: Colonic polyps, Colorectal cancer, Cancer genetics, Cancer syndrome, Cell signaling, Case report

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.