Abstract: Objective: To study the genetic etiology of a patient with non-syndromic tooth agenesis (NSTA) in a family. Methods: Peripheral blood of the proband and family numbers was collected, and whole-exome sequencing technique and bioinformatics tools were used to detect and analyze variants separately. After identifying the candidate gene of the proband, the variant site was verified by Sanger sequencing. The secondary structure and three-dimensional(3D)model of the mutant protein were analyzed and compared with the wild type using Protean and I-TASSER software. Results: Both the proband and his mother carried the same novel heterozygous frameshift mutation (c.176delT, p.I59fsX149) in PITX2. This mutation altered homeodomain and OAR domain, which affected the activity of DNA binding and the ability to activate downstream genes. The prediction of secondary structure revealed a decrease in the number of α helices of the mutant protein, and 3D model showed significant spatial conformational changes. Conclusions: The PITX2 frameshift mutation (c.176delT) may be one of the causes of NSTA in the proband. Our study extends the mutation spectrum of PITX2, and provides clinical and genetic evidence for further exploration of the association between PITX2 and NSTA.

Key words: tooth agenesis, PITX2, whole-exome sequencing