Primary Failure of Eruption: Clinical and Genetic Findings in the Mixed Dentition

CONTROL ID: 2639647 TITLE: Primary Failure of Eruption: Clinical and Genetic Findings in the Mixed Dentition AUTHORS (FIRST NAME INITIAL LAST NAME): C. Grippaudo1, I. D'Apolito1, C. Cafiero1, B. Ricci1, S. A. Frazier- Bowers2 AUTHORS/INSTITUTIONS: C. Grippaudo, I. D'Apolito, C. Cafiero, B. Ricci, Dental Institute, Università Cattolica, Rome, ITALY|S.A. Frazier-Bowers, Department of Orthodontics, University of North Carolina, Chapel Hill, North Carolina, UNITED STATES| PREFERRED PRESENTATION TYPE: Oral CURRENT SCIENTIFIC GROUPS & NETWORKS: Craniofacial Biology ABSTRACT BODY: Objectives: Eruption disorders represent an enigmatic aspect of dental and orthodontic diagnosis. Since the discovery that Primary Failure of Eruption (PFE, MIM #125350) is due to a genetic defect, several mutations of the PTH1R gene have been identified as causative. This study aimed to refine our understanding of the phenotype:genotype correlation of PFE and PTH1R mutations in the mixed dentition. This characterization may lead to improved diagnostic approaches and provide the foundation for downstream mechanistic studies to understand the pathogenesis of PTH1R mutations. Methods: DNA was extracted from saliva samples of 29 patients (3 families and 23 unrelated individuals) who presented with clinical evidence of infraoccluded teeth. Mutational analysis was completed for the coding regions of PTH1R gene following PCR amplification and direct sequencing. Results: Eight of 29 cases revealed a heterozygous pathogenic variant in the PTH1R gene; 5 of 8 variants represent distinct mutations within the cohort. One mutation (c.1765 T>C p.Trp89Arg) was found to segregate within a family (n=3) represented by two generations. Mutational analysis using the dbSNP, HGMD and the ESP databases identified the mutations were previously unreported. In silico analyses of all variants further predicted a putative pathogenic effect. Extended clinical analysis of the cohrot verified that all the novel mutations co-segregated with the PFE phenotype that included affection of the mixed dentition. Six of the 8 patients carrying a functional PTH1R mutation were children in mixed dentition with one or more primary teeth affected. Conclusions: We report that PFE in the mixed and permanent dentition positively correlates with pathogenic mutations in the PTH1R gene. Further studies to identify additional genes and correlate the pathogenesis of PFE from mixed to permanent dentition are ongoing and forthcoming. (no table selected) TABLE FOOTER: (No Tables) (No Image Selected) KEYWORDS: Primary failure of eruption (PFE), orthodontics, Dental eruption, genetics, mixed dention. Support Funding Agency/Grant Number - Abstracts: Financial Interest Disclosure: NONE AWARDS: Group Author Abstracts - Abstract: Session Chair Volunteers - Abstracts: Not Interested Special Scheduling Needs - Abstracts: Student Status - Abstracts: No Student Other Designation - Abstracts: Abstract Submission - Track Selection: Clinician Track