Abstract: Objective: We collected a family with non-syndromic oligodontia, and tried to detect the genetic etiology. Methods: After the medical history, clinical examinations including imaging examination, and blood sample were collected, we isolated the genomic DNA and conducted the whole exome sequence (WES). All the results were aligned to the normal human genome, and verified by Sanger sequencing. A series of bioinformatics database such as Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomeAD), Single Nucleotide Polymorphism Database (dbSNP), Sorting Intolerant from Tolerant (SIFT), polymorphism phenotyping (PolyPhen-2), and Mutation Taster, were used for mutation screening and confirmation. Results: The proband of the family was congenital missing 22 permanent teeth, and his parents and little brother showed normal clinical manifestations. The consequences of WES indicated that the proband carried compound heterozygous WNT10A mutations [c.637A>G (p.G213S) and c.985C>T (p.R329X)]. Further studies confirmed that the proband's missense mutation c.637A>G(p.G213S) was inherited from his father, while the nonsense mutation c.985C>T (p.R329X) was inherited from his mother. The little brother did not carry any mutations. Conclusions: Our study revealed a novel WNT10A compound heterozygous mutation and its genetic origin in a family with non-syndromic oligodontia. This result can be used for genetic counseling and prenatal diagnosis, and will improve understanding the role of WNT10A mutations in the pathogenesis of congenital tooth agenesis.