Application Of Chromosome Karyotype Technique And High-thiroiughput Sequencing Technique In Fetal Congenital Heart Disease

Objective:This study studied the genetics of 57 families with congenital heart disease(CHD).On the one hand,the relationship between CHD and various genetic factors was studied.On the other hand,three genetic testing technologies were used in combination to make up for the deficiency of a single technology,so as to improve the detection rate,provide reliable genetic counseling for pregnant women and their families,and guide pregnancy.Method:Fetuses indicated by echocardiography as CHD were selected and induced after the informed consent was signed.After successful induction,chromosome karyotype analysis is performed first,for those with negative karyotype results,copy number variation sequencing(CNV-seq)is performed further,for those who still have negative results,and for those with high throughput whole exome sequencing(WES)is performed.Finally,in case of uncertain pathogenicity results and significance,pedigree traceability analysis was performed to provide detailed prenatal genetic counseling.Result:Of the 57 CHD fetuses,21(36.84%,21/57)showed abnormal results.Among them,4 cases(7.01%,4/57)were abnormal,3 cases were 21-trisomy,and 1 case was 18-trisomy.A total of 14 cases(26.42%,14/53)with abnormal CNV were detected by CNV-seq,among which 7 cases(13.21%,7/53)were definitely pathogenic and 7 cases(13.21%,7/53)had unclear clinical significance.The former included 3 cases of 22q11.2 microdeletion and 1 case each of 22q11.2 microdeletion,1q21.1q21.2 microdeletion,7p22.1 microdeletion and 8p23.3p23.1 microdeletion.Three cases of gene mutation were found by WES(7.69%,3/39).TSC1 and TSC2 genes were pathogenic mutations,and the significance of NOTCH1 gene was not clear.The other 36 cases(63.15%,36/57)did not find the related cause by the above detection method.In the genealogical analysis,it was found that both 15q11.2 microdeletion and NOTCH1 gene were inherited from fathers with normal phenotype.Conclusion:1)Chromosome aneuploidy,copy number variation and single gene mutation are related to the occurrence of CHD.CNV with unclear clinical significance and single gene mutation may be related to the occurrence of CHD.Increasing the sample size for study and retrospective analysis can improve people’s understanding of CHD.2)Chromosome karyotype can be used to detect chromosome number abnormality.By using CNV-seq,micro-duplication and micro-deletion can be detected.WES can be used to detect single nucleotide variation,insertion and deletion.The combination of the three techniques for prenatal genetic screening of CHD can make up for the deficiency of a single technique,improve detection rate,and realize detection from chromosome level to gene level,so as to provide sufficient theoretical basis for prenatal genetic counseling and guide pregnancy.3)In the genetic test of CHD,family entry can help to find the CHD phenotype with genetic effect,assess the risk of recurrence and confirm whether it is a new case.