The Study On The Correlation Of Mutation Sites And Clinical Phenotypes Of Primary Failure Of Eruption (PFE)

OBJECTIVE: By studying the clinical data of PFE patients and the related data collected from Pub Med/Medline/Cnki database to discusse the possible relationship between clinical phenotype and gene mutation site.METHODS: Patients who were clinically diagnosed with PFE over the past five years were enrolled in this study.Their information on clinical phenotypes,including patient's gender,age,affected sites,involved tooth position,abnormal teeth,skeletal pattern,family history,and PFE classification,was collected by clinical and imaging examinations.Gene detection was performed in patients who were clinically diagnosed with PFE.Gene DNAs were extracted from the peripheral blood.Parathyroid hormone receptor 1(PTH1R)gene was amplified by polymerase chain reaction(PCR),and PTH1 R gene was sequenced to confirm the mutation site.According to the PRISMA guideline,the following search terms were retrieved systematically from the Pub Med/Medline/Cnki databases: “primary failure of tooth eruption”,“primary failure of eruption”,“tooth eruption failure”,and “PFE”.Eligible articles were screened out,from which the data for cases of PFE were acquired.All case data acquired were analyzed statistically.According to the sequence variant nomenclature developed by HGVS,cases of PFE were divided into an exon group,an intron group and an SNP group based on where the variant site was.Statistical methods were used to investigate the relationship with clinical manifestations among different groups.RESULTS: Clinically,data were acquired from a total of six patients with PFE.Of them,there were four males and two females;one patient had mixed dentition,and five had permanent dentition.Among patients with permanent dentition,molar involvement was found in only one patient,while premolar and molar involvement was identified in four patients;one had a definite family history and four did not have;two had concomitant dental abnormalities and there did not;two had unilateral involvement and three had bilateral involvement;two had maxillary involvement merely,and three had maxillary and mandibular involvement;two had Type II PFE and three had Type III PFE;one had skeletal I,and four had skeletal III.PTH1R gene was detected in a total of four patients with PFE.Of them,one had intron mutation,two had exon mutation,and one had SNP.Twenty-one eligible PFE-related articleswere identified from the Pub Med/Medline/ Cnki databases.The total of 322 PFE cases were collected.(including six PFE cases in our hospital)Mutated PTH1 R gene was identified from 83 patients in total.Of them,clinical data were available for 57 patients(38 in the exon group,14 in the intron group,and fivein the SNP group).In the exon group: three(9.1%)had unilateral involvement,and 30(90.9%)had bilateral involvement;seven(22.5%)had maxillary involvement merely,two(6.5%)had mandibular involvement merely,and 22(71.0%)had maxillary and mandibular involvement;two(16.7%)had molar involvement merely,and 10(83.3%)had premolar and molar involvement;one(7.7%)had skeletal I,one(7.7%)had skeletal II,and 11(84.6%)had skeletal III;29(70.8%)had a family history,and seven(29.2%)did not have;two(10.5%)had Type I PFE,one(5.3%)had Type II PFE,and 16(84.2%)had Type III PFE.CONCLUSION: The exon of PTH1 R gene in PFE patients is more prone to mutation,and PFE patients with mutation in exon have a clear family history and more serious symptoms,usually involving premolars,and mostly involving bimaxillary and bilateral.The intron group and SNP group did not show obvious characteristics.