Recently, the IRF6 contribution that was reported for Van der Woude syndrome and non-syndromic oral clefts was extended to isolated tooth agenesis. Here we report the first study that tries to replicate this finding and we provide further evidence that IRF6 contributes to isolated tooth agenesis. Fifty-two sporadic tooth agenesis cases and their parents were studied. DNA samples were obtained from whole blood or saliva samples. Genotyping was performed by TaqMan assays. Linkage disequilibrium analysis and transmission distortion of the marker alleles were performed. A haplotype involving the most 5'IRF6 markers was associated with sporadic tooth agenesis (p = 0.006). An association could still be seen when only cases with at least one missing incisor (p = 0.01) and cases with at least one missing premolar (p = 0.004) were included in the analysis. (C) 2008 Elsevier Ltd. All rights reserved.