Novel missense mutation in PAX9 gene associated with familial tooth agenesis

PAX9 is a transcription factor deeply involved in the gene networks that regulate odontogenesis. To date, only a restricted number of mutations in this gene have been associated with non‐syndromic tooth agenesis. Six families segregating non‐syndromic oligodontia/hypodontia were screened for mutations in PAX9 gene. A novel missense mutation lying in the exon 2 close to the end of the paired domain in three families was identified. Heterozygous mutation C503G is expected to result in an alanine‐to‐glycine amino acid change in residue 168 (Ala168Gly), which is invariably conserved among several species. The alanine–glycine change might lead to protein structural alteration because of the unique flexibility properties of glycine. Three mutations in intron 2 were also detected. Variations IVS2–109G>C, IVS2–54A>G, and IVS2–41A>G were identified in both affected and unaffected members of the sample; however, these polymorphic variants may be involved in the phenotype as one proband showing all three intronic mutations in homozygosis was affected with the most severe oligodontia within the sample.