A novel PAX9 mutation found in a Chinese patient with hypodontia via whole exome sequencing.

OBJECTIVE: To investigate a novel gene mutation in a Chinese patient with non-syndromic hypodontia. SUBJECTS AND METHODS: Mutation analysis was carried out by whole exome sequencing. Bioinformatics tools were used for the biophysical predictions of the mutative protein. Luciferase reporter assay was performed to analyse the effects of mutation on protein function. PAX9 and BMP4 gene expression from mutant cells was detected by qRT-PCR. RESULTS: A novel heterozygous mutation (c.G1057A) was detected in the patient but was not found in the controls. The novel missense mutation led to a Val111Met substitution in the paired box domain which was completely conserved evolutionarily, as analysed by dbNSFP. The mutation was predicted to be disease-causing and harmful using MutationTaster and CADD, respectively. Protean of Lasergene showed that this mutation may lead to ß-region shortening in the mutant protein compared to the wild type. Luciferase reporter assay indicated that the mutated protein reduced the transactivation activity of PAX9. This mutation led to increased levels of PAX9 transcript and reduced levels of BMP4 transcript, likely due to compensatory activation and lower transactivation activity of mutant PAX9. CONCLUSION: This novel mutation (c.G1057A) in PAX9 caused hypodontia by altering PAX9 gene function and downregulating BMP4 gene expression.