Molecular Genetics Approaches To Understand The Congenital Tooth Agenesis&Cases Report

Tooth agenesis,a congenital anomaly,commonly seen in population,has divided into several categories according to different criterions.Based on whether there are other symptoms,tooth agenesis can be classified into selective tooth agenesis and syndromic tooth agenesis.According to the number of missing teeth(excluded the third molar),it is grouped into hypodontia(less than six permanent teeth missing),oligodontia(six or more than that of permanent teeth missing),and anodontia(all the missing).According to the inheritance,tooth agenesis may occur as sporadic or familial,most of which were the latter inheritance,inherited by autosomal dominant,autosomal recessive and X-linkage pattern.More than eighty genes were considered to be related with tooth agenesis,including MSX1,PAX9,AXIN2,WNT10A,EDA,EDAR,EDARADD,TP63 et al.EDA was one of the genes that related to both the selective and syndromic tooth agenesisObjectives:1.To investigate Chinese families with congenital tooth agenesis by the proband confirmation method.2.To screen the disease-causing mutations on EDA,EDAR and TP63 genes by PCR and direct sequencing in the collected families with tooth agenesis.Methods:1.After written informed consents signed,we inquired the illness history,checked their symptoms and physical conditions in detailed.Phenotypic characteristics and genetic modes were analyzed.After that,5 to 10 mL peripheral venous blood samples of some of the members in families were collected.Modified salting out procedure was used to extract the Genomic DNA.2.Direct sequencing was used to screen mutations on EDA,DAR and TP63 genes.Results:1.We ascertained six unrelated pedigrees(five syndromic and one selective),a total of eight patients,who were from Fujian,Jiangxi,Sichuan,and Shanghai.Six of the eight patients with congenital tooth agenesis were accompanied by typical or part of a typical performance of EDs.2.Four(family 1,2,3,6)of the six pedigrees were sequenced on exons of TP63,EDR and EDA genes.Two missense nucleotide variations(TP63 c.184G>C,p.62V>L and EDAR c.751 A>G,p.251 M>V)and one large fragment deletion(EDA Del Ex 3)were confirmed.Conclusions:1.We reported six tooth agenesis pedigrees,with five syndromic pedigrees and one selective tooth agenesis pedigree.2.Three identified mutations are possibly responsible for the disease phenotypes in three families with congenital tooth agenesis respectively,which expand the mutation spectrums of Chinese patients with tooth agenesis.