Genetic Etiology Analysis Of Fetal Congenital Heart Disease

Objective:To discuss the genetic etiology of congenital heart disease by karyotyping,Copy number variation sequencing and whole-exome sequencing of amniocytes of prenatally fetuses with congenital heart disease.Methods:1.There are 104 pregnant women in total who underwent prenatal diagnosis due to"fetal congenital heart disease"in Shanxi Maternal and Child Health Hospital from March 2019 to November 2021 were selected as the research objects.2.Amniotic fluid was extracted from 104 pregnant women with abnormal fetal heart structure by ultrasound,and karyotype analysis and CNV-seq detection were performed on each specimen to compare and analyze the fetal chromosomal abnormalities detected by the two techniques.Results CHD fetuses with normal karyotype and CNV-seq were tested by WES after informed choice by pregnant women and their families,and their pregnancy outcomes were followed up.3.SPSS 23.0 Software was used to analyze statistical data,and the measurement data was expressed as(mean±standard deviation).Comparison of rates between groups was performed byχ~2test,and P<0.05 was considered statistically significant.4.Obtain the approval of the Ethics Committee of Shanxi Maternal and Child Health Hospital,and all research subjects signed informed consent.Results:1.The karyotype analysis and CNV-seq detection of the 104 samples were successful,with a success rate of 100%.2.The chromosome karyotype analysis detected 88 cases(84.62%)of normal fetal chromosomes and 16 cases(15.38%)of abnormal chromosomes.Among them,chromosome structure abnormality in 2 cases(1.92%);14 cases(13.46%)had abnormal chromosome number,including 6 cases(42.86%)of trisomy 21,4 cases(28.57%)of trisomy 18,1 case(7.14%)of trisomy 13,and 1 case of 45,X(7.14%),47,XYY in 2 cases(14.29%);.3.CNV-seq detected 74 cases(71.15%)of normal chromosomes(normal,benign copy number variation and possibly benign copy number variation)and 30 cases(28.85%)of chromosomal abnormalities,including 7 cases(6.73%)of copy number variation of unknown clinical significance,23 cases(22.12%)of chromosomal abnormality were identified as pathogenic.Among the 88 samples with normal karyotype analysis,CNV-seq detected 7 cases with definite pathogenic copy number variation,accounting for 7.95%(7/88).4.Compared with karyotype analysis,the detection rate of chromosomal abnormalities by CNV-seq is higher than that of karyotype analysis,and the difference is statistically significant(P<0.05);CNV-seq combined with karyotype analysis has a higher detection rate of chromosomal abnormalities In the analysis of chromosome karyotype alone,the difference was statistically significant(P<0.05).5.Among the 104 CHD fetuses,there were 75(72.12%)single cardiac malformations and 29(27.88%)multiple cardiac malformations;the detection rate of chromosomal abnormalities in multiple cardiac malformations was higher than that of single cardiac malformation(48.28%vs 21.33%),the difference between the two groups was statistically significant(P<0.05).6.Among the 104 CHD fetuses,there were 65 cases(62.5%)of pure cardiac malformation and 39 cases(37.5%)of combined extracardiac malformation;the detection rate of chromosomal abnormality combined with extracardiac malformation was higher than that of pure cardiac malformation(41.03%vs 21.54%),the difference between the two groups was statistically significant(P<0.05).7.Among the 104 CHD fetuses,a total of 23 fetuses with pathogenic chromosomal abnormalities were detected,including:6 cases of trisomy 21,6 cases of 22q11.2microdeletion and microduplication,4 cases of trisomy 18,47,XYY in 2 cases,1 case of trisomy 13,1 case of 45,X and 3 cases of other chromosome deletion or duplication.8.Among 74 fetuses with cardiac malformation with no chromosomal abnormalities detected,After informed selection,3 cases of CHD fetuses with normal chromosomal karyotype analysis and copy number variation were tested by WES,of which 1 case was detected FLNA gene(filamin A)mutation was found,and no related mutation was found in the remaining 2 cases.Conclusion:1.In CHD fetuses,CNV-seq has a higher rate of chromosomal abnormalities than karyotype analysis.2.In some CHD fetuses with no abnormality in karyotype analysis and copy number variation,WES can detect pathogenic genes related to CHD.3.The rational combination of karyotype analysis,CNV-seq and WES can effectively improve the detection rate of chromosomal and gene abnormalities in CHD fetuses and reduce the birth of CHD children caused by genetic factors.4.Compared with single heart malformation,CHD fetuses with multiple heart malformations have a higher rate of chromosomal abnormalities.5.Compared with pure cardiac malformation,CHD fetuses with extracardiac malformation or abnormal ultrasound soft index have a higher chromosomal abnormality rate.