AXIN2 Contributes to Isolated Tooth Agenesis

Objectives: Tooth agenesis is a common congenital disorder that affects almost 20 percent of the world's population. A number of different genes have been shown to be associated with cases of tooth agenesis including MSX1, PAX9, TGFA, and recently AXIN2. AXIN2 has also been associated with a number of different colorectal polyp and carcinoma disorders. In this study we sought to determine if markers in AXIN2 are associated with isolated tooth agenesis. Methods: Blood, saliva, and/or cheek swab samples were obtained for DNA analysis from 167 case/parent trios of tooth agenesis families. Probands had at least one developmentally missing tooth, excluding third molars. Genotyping was performed using TaqMan chemistry. Transmission distortion tests of the marker alleles were performed. Samples were analyzed as a total group and subgrouped in cases with at least one missing incisor, cases with at least one missing premolar, and cases with a positive family history for tooth agenesis. Results: AXIN2 was associated with cases with at least one missing incisor (p=0.037). Conclusion: Our work further supports a role of AXIN2 in human tooth agenesis and for the first time suggests AXIN2 is involved in sporadic forms of common incisor agenesis. NIH Grant 5TL1RR024155-02.