The Orthodontic Treatment Scheme for Primary Failure of Eruption Patient without PTH1R Mutation

Abstract Primary failure of eruption (PFE) is observed as a defect in the tooth eruption mechanism with the heterozygous mutations of parathyroid hormone receptor gene (PTH1R). The present study reported 2 families suffered from nonsyndromic tooth eruption disorder in successive generations. Genetic analysis and standardized assessments, including clinical and radiographic examinations, of the dental condition of all patients were performed to give a clear understanding of the disease. The mutation of PTH1R was detected in patient II-1 (Family I) by PCR and sanger sequencing. Sequencing analysis reviewed heterozygous presence of c.439C>T in exon 2 of PTH1R. According to the UniprotKB database, PTH1R is highly conserved among several mammalian species. RNA-seq was performed to further analyze the role of PTH1R in tooth development and eruption. It showed that during tooth development, the expression of PTH1R decreased in the early stage of tooth development in rat and mouse. However, the mutations of PTH1R were not detected in 2 patients from family II. With extensive analysis of the radiographs and physical examination, we attempted to use orthodontic methods to create enough room for tooth eruption, which shows therapeutic result to the submerged tooth. The results suggested new orthodontic scheme for the PFE patient without PTH1R mutation. Both clinical and genetic diagnosis should be considered in the treatment planning.