一个单纯性先天缺牙家系的临床表现及PAX9、MSX1、AXIN2基因突变分析

Clinical Research on a Non-syndromic Hypodontia Family and Sequence Analysis of PAX9,MSX1 and AXIN2 Genes

目的对一个单纯性先天缺牙家系进行缺牙临床表型的分析及PAX9、MSX1及AXIN2基因突变检测,探讨单纯性先天缺牙的可能发病机制。方法收集一个单纯性先天缺牙家系的临床资料(包括口腔检查和影像学资料)和静脉血标本,提取DNA,采用PCR分段扩增PAX9基因的1-4号外显子,MSX1基因的1、2外显子及AXIN2基因的1-10号外显子,通过基因测序,分析该家系PAX9、MSX1及AXIN2基因是否存在突变、突变方式及位点,并进行可疑致病突变的验证分析。结果该家系中单纯性先天缺牙患者的缺失牙位数目最多为第二前磨牙和尖牙,均占该家系缺牙数目的41.2%。基因检测发现PAX9基因2个SNP位点:c.717C>T、c.718G>C;MSX1基因未检测到突变;AXIN2基因发现3个SNP:c.432.T>C、c.1365.A>G、c.2062.C>T。结论该家系的单纯性先天缺牙可能是由AXIN2基因c.2062.C>T改变和PAX9基因c.717C>T、c.718G>C改变共同作用下形成的。

Objective To investigate the clinical traits of a non-syndromic hypodontia family and to detect the genetic mutations in PAX9,MSX1 and AXIN2 genes,so as to discuss the pathogenic mechanisms of the disease.Methods The clinical data,including complete oral examination and panoramic radiographs,of a non-syndromic hypodontia family were collected.DNA was extracted from the venous blood.Gene fragments of PAX9 gene exon1-4,MSX1 gene exon1-2 and AXIN2 gene exon1-10 were amplified by PCR.Mutations in PAX9,MSX1 and AXIN2 genes were detected.The suspected pathogenic mutations were confirmed and analyzed.Results The most absent teeth in the family were the second premolar and canine,both accounting for 41.2% of the total missing teeth.Two SNPs,c.717〉CT and c.718〉GC,were detected in PAX9 gene.Three SNPs,c.432.T〉C,c.1365.A 〉G and c.2062.C〉T,were detected in AXIN2 gene.None mutation was found in MSX1 gene.Conclusions The non-syndromic hypodontia in the family may be caused by the combined action of AXIN2 gene change,c.2062.C〉T,and PAX9 gene changes,c.717C〉T and c.718G〉C,as well the effects of the environment.