significance of PTH1R variants of an Italian sample with primary afilure of eruption

AIM: Primary failure of eruption (PFE) is characterized by non-syndromic eruption failure of not ankylosed teeth, which fail in their eruptive process partially or completely, without any systemic disease or mechanical interference identifiable. This condition is different from the mechanical eruption failure (MFE) due to a mechanical obstacle. Primary eruption failure is an eruptive anomaly whose cause must be found in heterozygous variants of the gene encoding the Parathyroid receptor 1 (PTH1R, OMIM * 168468), located on chromosome 3p21.31. Aim of this work is to identify clinical and radiographic characteristics that distinguish PFE from other eruptive disorders, by comparing the clinical characteristics between positive and negative patients for PTH1R variants and by observing the genotype/phenotype correlations in positive patients in light of the differences in the type of variants found. Furthermore variants significance has been analyzed evaluating their pathogenicity through a comparison with those reported in dedicated databases. In this way, the combination of genetic information and clinical data is used to expand knowledge on the genotype-phenotype correlation of PFE. METHODS: A data set of 38 patients (22 males and 16 females) with eruption disorders was collected at the Università Cattolica del Sacro Cuore in Rome. Clinical examination and panoramic x-ray were used to assess the dental phenotype and the localization of the eruption problems. Patients’ selection was based on the clinical characteristics described by Stellzig-Eisenhauer et al. For DNA extraction, salivary cell samples were collected using special "salivary brush" usually used for these types of samples. RESULTS: After mutational analysis, patients with clinical PFE were placed into 2 categories: 17 with PTH1R variants and 21 patients negative for variants in PTH1R. In patients positive for the genetic test, were found typical features in agreement with phenotypic signs suggested by literature, such as involvement of posterior teeth, involvement of the distal teeth to the most mesial affected, coronal bone resorption of the affected teeth, involvement of both deciduous and permanent teeth, altered vertical growth of the alveolar process and posterior open-bite. In patients without variants a less clear phenotype has been found, which often involved only one tooth or a single arch. In our patients 13 PTH1R variants were identified: 8 reported in the public databases, 5 novel and probably pathogenic. CONCLUSIONS: Our results suggest that clinical and radiographic exams can be enough to give a prognostic preliminary opinion about the presence of PTH1R variants, but that the genetic analysis is indispensable for a certain diagnosis, in order to avoid therapeutic errors. So we conclude that the genetic analysis and further genotype-phenotype correlation studies result indispensable to focus on the molecular and biological basis of PFE and, especially, to avoid unsuccessful orthodontic treatments.