Mutations in the PTH1R gene have been associated with the non-syndromic craniofacial phenotype, primary failure of eruption (PFE), which is marked by clinical eruption failure of secondary teeth in the absence of mechanical obstruction. The recent finding that mutations in the PTH1R gene cause PFE confirms the genetic basis of eruption but also suggests the etiology eruption disorders. To date, 4 coding and 3 splice-site mutations have been identified as causative of PFE in families. Clinical diagnosis of PFE versus ankylosis is challenging; recent phenotypic studies have shown a broad spectrum of clinical characteristics. Objective: The objective of our study is to expand the definition of the clinical presentation of PFE and test the hypothesis that eruption failure resulting from a genetic mutation includes a broad clinical spectrum. Methods: Study participants (N=27) were characterized phenotypically based on the following criteria: intra- versus supra-osseous eruption failure, uni- or bilateral affection, and Type I versus Type II presentation. Direct sequencing of PCR products was carried out to analyze the coding region and intron-exon boundary of the PTH1R gene in affected individuals. Results: Phenotypic analysis revealed that 100% of affected individuals included an infraoccluded permanent first molar; bilateral eruption failure occurred in 63% of cases. Of the individuals analyzed genetically, one nuclear family segregated a novel 1094 del G mutation in the coding region of PTH1R. The corresponding phenotypic presentation of the proband revealed a uni-lateral supra-osseous affection with infra-occluded primary and permanent first molars in upper and lower right quadrants. The proband also presented with a mild skeletal class III malocclusion. Conclusions: The identification of the PTH1R 1094 del G frame shift mutation confirms association of PTH1R with eruption failure of permanent and primary dentition. This work is supported by an AADR student fellowship and NIH RR00046.
Keywords: Genetics, Malocclusion, Molecular biology, Orthodontics and Osteoblasts/osteoclasts
See more of: Craniofacial Biology