IRF6 – Tooth Agenesis

IRF6 has been investigated as a candidate gene for nonsyndromic tooth agenesis (MONDO:0005486) based on its role in orofacial development and syndromic clefting. A Hungarian case-control study of 192 hypodontia and 17 oligodontia cases versus 260 controls found no significant association of IRF6 T/C rs764093 with tooth agenesis, in contrast to PAX9 and MSX1 effects (PMID:23964635). Targeted MIP sequencing of IRF6 in 67 nonsyndromic tooth agenesis patients identified three rare missense variants, all inherited or with unavailable parental data, and no de novo changes in the agenesis cohort, while a retrospective review revealed lip pits only in a de novo case from the orofacial cleft group (PMID:27834299). This sequencing effort yielded variants such as c.635G>A (p.Ser212Asn).

Overall, IRF6 exhibits at most a modest, population-specific risk for tooth agenesis without evidence of Mendelian segregation or functional studies in dental tissues. Negative and inconsistent association results, combined with the absence of pathogenic segregating alleles in affected families, argue against a monogenic role. Additional replication and tooth-specific functional assays are required.

Key Take-home: Current data do not support IRF6 as a major Mendelian cause of nonsyndromic tooth agenesis.

References

• Acta odontologica Scandinavica • 2014 • Complex analysis of multiple single nucleotide polymorphisms as putative risk factors of tooth agenesis in the Hungarian population. PMID:23964635
• Journal of dental research • 2017 • Novel IRF6 Mutations Detected in Orofacial Cleft Patients by Targeted Massively Parallel Sequencing. PMID:27834299

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