Mutations in the PAX9 Gene Associated With Non-syndromic Oligodontia

Objectives: Congenital tooth agenesis is one of the most common developmental anomalies in human and it may contribute to masticatory dysfunction, speech alteration, aesthetic problem and malocclusion. The paired-domain transcription factor PAX9 plays a critical role in tooth development, as heterozygous mutation of PAX9 is associated with non-syndromic tooth agenesis. The aim of the study was to search for PAX9 mutation in 120 patients with non-syndromic tooth agenesis.
Methods: In a large cohort of 120 patients with non-syndromic tooth agenesis, 4 exons of the PAX9 gene have been sequenced. All the patients were congenital absence of six or more permanent teeth excluding third molar.
Results: 11 mutations in PAX9 were identified in 120 unrelated patients with tooth agenesis. 9 of them (c.140G>C, c.167T>A, c.332G>C, c.194C>A, c.271A>T, c.146delC, c.185_189dup, c.256_262dup, c.592del G) are novel mutation. The 11 mutation consists of 4 missense mutations, 2 nonsense mutations and 5 frameshift mutations. All the mutation were in the exon 2 of PAX9, suggesting that exon 2 a notable hot spot mutation region in the PAX9 gene. Phenotypic analysis shows that the maxillary first molar is the most common missing tooth in patients with PAX9 mutation; the maxillary canine was rarely involved.
Conclusions: Our results show that PAX9 mutation accounted for 9.12% of tooth agenesis cases. These findings greatly expand the mutation spectrum of tooth agenesis and suggest that PAX9 can be regarded as a marker gene for tooth agenesis.