Human Primary Failure of Eruption (PFE), a rare anomaly of tooth eruption, has no known genetic and molecular basis. It commonly affects permanent posterior teeth that show no structural defects and are not impeded by supernumerary teeth or soft tissues. It is poorly characterized and remains one of the most difficult dental conditions to diagnose and treat. Our current understanding of the biology of tooth eruption implicates the dental follicle, a loose connective tissue sac surrounding the tooth organ, in mediating the cascade of signaling events that are indispensable for this process. Coincident with this is the finding that a transcription factor, Runx2/Cbfa1, is dominantly expressed in the dental follicle and its derivatives during tooth eruption. In mice and man, defects in RUNX2 result in cleidocranial dysplasia (CCD), which also has a failure in tooth eruption as a hallmark feature. Taken together, this suggests that PFE may represent a phenotypic variant of CCD. Objectives: The aim of this study was to determine if a disruption of RUNX2 is responsible for PFE. Methods: Blood samples were collected from a unique population of individuals/families affected with PFE. Upon isolation of genomic DNA, PCR-based mutational analysis of the coding regions of human RUNX2 was performed by direct sequencing. Results: Our analysis has revealed an adenine to guanine conversion in the promoter region of RUNX2 in one affected individual. No mutations have been detected in other affected individuals to this point. Conclusion: The identification of a novel mutation in RUNX2 implicates a role for it in the pathogenesis of PFE. Additionally, the lack of mutations in RUNX2 in other affected individuals suggests other genes may also be responsible for PFE. Supported by NIH/NIDCR Grant DE13368 (RDS), T35DE07252-09 (OJD), DE14237 (HK), and AAOF grant (RDS).

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Back to the 81st General Session of the International Association for Dental Research (June 25-28, 2003)

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