A Novel Mutation Of Gene Runx2 In Chinese Patients With Delayed Tooth Eruption

Delayed tooth eruption (DTE) may occur in both primary and permanent dentition. In clinic, DTE in permanent teeth was more common. The number of teeth affected by DTE varies over a large range. Often, DTE can have a significant impact on a patient's daily life.The process of normal eruption is still a controversial topic. Mechanisms that could lead to DTE have been reported to have a relationship with some local and systemic conditions and genetic disorders, of which the last two factors, systemic conditions and genetic disorders, occurred more frequently. And CCD was the most frequently encountered disorder in genetic factors that could cause DTE.CCD is an autosomal dominant skeletal dysplasia characterised by patent sutures and fontanelles, abnormal clavicles, short stature, DTE, supernumerary teeth and a variety of other skeletal changes. Mutations of gene Runx2 have been identified as being responsible for CCD.Few studies have been published regarding the mechanisms causing DTE in Chinese patients. The aim of this study was to present two Chinese DTE patients with a clinical diagnose of CCD at our department and discusss its potential mechanism that whether it is due to mutations of Runx2 gene.PartⅠ: Clinical research of patients with DTE1. Main methods We collected two DTE patients in clinic. All patients were examined in a dental chair. Informations regarding age, gender, medical history, family history, conditions of teeth eruption, as well as other abnormalities were recorded. Based on this, radiological examinations and serologic examinations were carried out.2. Main resultsCase 1: This is a familial case. The proband showed typical CCD phenotypes, with hypoplastic clavicles, open fontanelles, failure of eruption of multiple permanent teeth, supernumerary teeth, cross bite and short stature.Case 2: The proband showed unusual clinical features, with delayed eruption of primary teeth, failure of eruption of all permanent teeth, symmetrical non-specific change of buccal mucosa and bony spur of mandible, congenital arthrogryposis of both hands, but no family history. Serologic examinations showed ALP was a little higher (140U/L, reference value 15-121 U/L).3. Main conclusionsCase 1 showed typical CCD phenotypes, and we made the diagnose of CCD.Case 2 showed unique clinical festures, which helped us to rule out most local and systemic conditions that could lead to DTE and suggested it might be because of a genetic disorder. And the diagnose of CCD was made at last. PartⅡ: Mutations of Runx2 in Chinese CCD patients1. Main methods Genomic DNA was extracted from the peripheral blood using a Whole Blood Genomic DNA lsolation Kit (Dingguo, Beijing, China). Exons 0-7 of Runx2 was amplified by PCR. PCR products were purified, cloned into pMD18-T vector and transformed into DH5α. The positive clone was then sequenced.2. Main resultsA novel mutation (c.73C>T,R25W) was identified within exon1 of Runx2 in case 1.3. Main conclusionsThe diagnose of CCD in case 1 was proved by the finding of a novel mutation of Runx2 gene. In case 2, the proband showed unusual clinical features, with delayed eruption of primary teeth and all permanent teeth. However, mutations of Runx2 did not found in case 2. This suggested it might be in relationship with other genetic disorders or local conditions, such as Gardner syndrome or mucosal barrier, which still needs further study.