AXIN2 Gene, Known Mutation
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Oligodontia, defined as the congenital absence of 6 or more permanent teeth, can occur as either an isolated finding or as part of an underlying syndrome. AXIN2 is one of several genes that have been associated with nonsyndromic oligodontia. In a subset of patients, mutations in the AXIN2 gene have been found to be associated with a combined oligodontia-colorectal cancer syndrome. Oligodontia-colorectal cancer syndrome is a rare hereditary cancer syndrome. One study of a Finnish family with AXIN2-related oligodontia-colorectal cancer syndrome identified colorectal cancer in 67% (6 of 9) of family members with oligodontia and a confirmed AXIN2 mutation. The AXIN2 mutation in this family was inherited in an autosomal dominant fashion. In the same study, a de novo AXIN2 mutation was identified in a 13-year-old patient with oligodontia but no history of colorectal cancer.
Somatic AXIN2 mutations have been identified in mismatch repair-deficient colorectal tumors and have been shown to cause accumulation of beta-catenin and subsequent activation of T-cell factor -dependent transcription. These findings support the role of AXIN2 in tumorigenesis.
Note: This test is appropriate for predictive testing in families in which a point mutation or small insertion/deletion/duplication has been identified.
SDEL / Single-Gene Large Deletion and Duplication Analysis is appropriate for predictive testing in families in which a large deletion or duplication (whole exon or multi-exon) has been identified.
If a familial mutation has not been previously identified, AXINS / AXIN2 Gene, Full Gene Analysis is more appropriate.
Predictive testing for oligodontia-colorectal cancer syndrome when a point mutation or small insertion/deletion/duplication has been identified in an affected family member
All detected alterations will be evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(1) Variants will be classified based on known, predicted, or possible pathogenicity, and reported with interpretive comments detailing their potential or known significance.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order AXINS / AXIN2 Gene, Full Gene Analysis.
Analysis is performed for the familial mutations provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with hereditary colorectal cancer.
We strongly recommend that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.
A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Richards CS, Bale S, Bellissimo DB, et al: ACMG recommendations for standards of interpretation and reporting of sequence variations: revisions 2007. Genet Med 2008:10(4):294-300
2. Lammi L, Arte S, Somer M, et al: Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet 2004;74:1043-1050
3. Liu W, Dong X, Mai M, et al: Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating beta–catenin/TCF signaling. Nat Genet 2000;26:146-147
4. Mai M, Qian C, Yokomizo A, et al: Cloning of the human homolog of conductin (AXIN2), a gene mapping to chromosome 17q23-q24. Genomics 1998;55:341-344
5. Dong X, Seelan RS, Qian C, et al: Genomic structure, chromosome mapping and expression analysis of the human AXIN2 gene. Cytogenet Cell Genet 2001;93:26-28