Segregation of PTH1R SNP with Familial Primary Failure of Eruption (2014)

Undergraduates: Paul Lee, Heather Hendricks

Faculty Advisor: Sylvia Frazier-Bowers
Department: Biology

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Primary failure of eruption (PFE) is characterized by non-syndromic eruption failure of secondary teeth in the absence of mechanical obstruction. Recent studies have supported the association between mutations in the Parathyroid Hormone 1 Receptor (PTH1R) and PFE. Clinical differentiation between PFE and ankylosis presents a challenge in orthodontics, and phenotypic studies have shown a broad spectrum of clinical characteristics. Objective: The objective was to investigate the causal relationship of PTH1R mutations in multi-generational families with PFE. Method: Pedigree analysis by inspection and assessment of clinical records was completed for one multi-generational family (N=10) with 8 affected and 2 unaffected individuals. Genetic samples were obtained for 4 affected individuals; direct sequencing of PCR products to analyze the coding regions and intron-exon boundary of the PTH1R gene was completed for 3 samples. Result: Pedigree analysis revealed a familial segregating autosomal dominant trait. A c.1389 T>C variation was found in the coding region of the PTH1R gene for affected individuals (N=3). This known heterozygous alteration is a putative non-functional alteration. Conclusion: PFE results in the failure of the eruption mechanism and orthodontic response of affected teeth ¿ which makes appropriate diagnosis and treatment imperative. Identification of the putative PTH1R SNP that segregates with the phenotype warrants further investigation to determine causality.