Congenitally missing teeth (tooth agenesis) represents the most common craniofacial anomaly in man, affecting up to 20% of the population worldwide. Tooth agenesis is a clinically heterogeneous disorder affecting specific tooth types at different rates. Recent evidence also confirms the role of genetic heterogeneity in this common dental anomaly, with two genes, MSX1 and PAX9, contributing to the majority of cases published. Previous studies have associated mutations in PAX9 with molar oligodontia, while others have associated mutations in MSX1 primarily with premolar hypodontia. Most of these studies have focused on individuals who are otherwise normal and affected with this disorder.
Objective Our objective was therefore to determine if alterations in MSX1 and PAX9 might also be responsible for tooth agenesis in families also affected with dental syndromes including tricho dento osseous syndrome (TDO) or amelogenesis imperfecta (AI).
Methods To test whether mutations in MSX1 and PAX9 are responsible for cases of tooth agenesis occurring with specific dental anomalies, we used direct sequencing of PCR products. Clinical examination, pedigree analysis, followed by PCR-based mutational analysis of MSX1 was carried out for affected individuals and unaffected relatives.
Results Pedigree analysis revealed that tooth agenesis was transmitted as an autosomal dominant trait in all families examined. Direct sequencing of the coding region revealed the presence of non-synonymous SNPs in MSX1 and PAX9 for affected and unaffected family members.
Conclusion Our results support the conclusion that tooth agenesis is due to genetic heterogeneity and suggest that MSX1 may cooperate with PAX9 in the patterning of human dentition, and also that a unique haplotype may be present in families segregating tooth agenesis and either TDO or AI. Supported by the AAOF (S.F.-B.) and NIH grant 1K23RR17442-01 (S.F.-B.).
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