Frequency of common polymorphisms A240PPAX9 and A34GMSX1 in tooth agenesis

Objectives: PAX9 and MSX1 mutations have been shown to cause non-syndromic tooth agenesis of a predominantly molar and premolar pattern, respectively. So far, the impact of frequent polymorphisms A240P in PAX9 and A34G in MSX1 on tooth agenesis has been difficult to evaluate. We have examined the prevalence of these MSX1 and PAX9 mutations in two populations: 50 non-related individuals with varying degrees of non-syndromic tooth agenesis and 50 unaffected controls.

Methods: We performed mutational analysis by PCR amplification of the coding regions of both PAX9 and MSX1, followed by sequencing of all subjects. The number of heterozygous individuals and the difference in polymorphic allele frequency between affected and unaffected individuals was assessed using chi square statistics.

Results: Sequence analysis revealed a A34G mutation in the homeodomain of MSX1 and A240P mutation in exon three of PAX9. A larger percentage of affected subjects display the MSX1 A34G mutation: 46% versus 30% in the unaffected group. Heterozygotes are more common among affected individuals at a statistically significant level (p= 0.031). Homozygotes of either allele are of similar frequency in both groups. The allele frequency of the polymorphic MSX1 allele is higher in the affected group than in the unaffected (0.29 versus 0.23). The PAX9 A240P mutation is also more common in the affected group: 42% of affected individuals are heterozygotes while only 29% of unaffected probands are heterozygous for the mutation; however the difference is not statistically significant.

Conclusion: Our data demonstrate that the two common polymorphisms in MSX1 and PAX9 are more frequent in patients with tooth agenesis, although this difference reaches statistical significance only for patients who are heterozygous for the A34G polymorphism in MSX1. This suggests that the MSX1 polymorphism may contribute to tooth agenesis in these patients.

Supported by Baylor Oral Health Foundation (SPW); NIH U24-PEI6472 (RDS).