Detection Of Mutation In ZFPM2/FOG2Gene Coding Region In Patients With Tetralogy Of Fallot

ObjectiveTetralogy of Fallot (TOF) is a polygenic inherited congenital heart disease.The patients’ susceptibility to the disease has relationship with some specialgenes or genetic group of the chromosomes. Studies have shown thatZFPM2/FOG2genetic changes can lead to the occurrence of TOF. This studydetected the ZFPM2/FOG2gene coding region by polymerase chain reaction(PCR reaction) and DNA sequencing and explore its relationship with TOF.MethodsWe selected106patients of congenital heart disease from January2007toApril2009in Department of Congenital Heart Disease，the General Hospital ofShenyang Military Region who were diagnosed as tetralogy of Fallot. Age,gender between the control group and patient group had no significantdifference.110patients of normal volunteers were as control group. Peripheralvenous blood specimens from patient and control groups were extracted andgot the whole blood genomic DNA. Through polymerase chain reaction andDNA sequencing analysis, we detected the distribution of the mutation or singlenucleotide normality sites of ZFPM2/FOG2gene coding region of106TOFpatients. And verify the abnormal sites in110normal volunteers.ResultsBy DNA sequencing analysis of ZFPM2/FOG2exon8, we found23point mutations:two missense changes in exon2and the nature of the amino acidchanged; five new changes in intron6;15new changes in the coding regionof exon8in which1have been reported was related with the mutation sites ofdouble outlet right ventricle. These new discoveried point changes were notfound in the normal population of110cases. Two mutations were in theN-terminal transcriptional expression domain, a mutation was in the3zincfinger domain, a mutation located in the seven zinc finger domains. Inaddition, four known single nucleotide polymorphisms were also found in exon8.ConclusionIn our study, we found22mutant sites of ZFPM2/FOG2gene which had notbeen reported, including5non-coding regions,17coding regions. Among them,there was a synonymous mutation, the locus located in exon8;16mutant siteswere missense mutations, two in exon2and14in exon8. In addition, in thisstudy, we confirmed that five mutant sites which have been reported, of whichthere was4SNP sites and one mutant site. The results of our study confirmedthat ZFPM2/FOG2gene exon2,8is closely related to the occurrence of TOF.ZFPM2/FOG2gene mutation may lead to the occurrence of TOF.The specificity and sensitivity analysis of ZFPM2/FOG2to TOF showed thatalthough the sensitivity is not high, but the specificity is satisfactory, whereby,ZFPM2/FOG2gene may be useful in prenatal diagnosis and gene therapy ofTOF.