Application of chromosomal microarray analysis in congenital heart disease

Abstract

Objective: To investigate the relationship between different types of fetal congenital heart disease (CHD) and genetic factors, and to evaluate the application value of chromosomal microarray analysis in prenatal diagnosi s of fetuses with CHD. Methods: 122 fetuses diagnosed with CHD by prenatal fetal ultrasound or echocardiography in Weihai Maternal and Child Health Hospital and that underwent prenatal diagnosis by amniocentesis from June 2016 to December 2020 were included as research subjects. Karyotype analysis, chromosomal microarray analysis technology, and sNP-array technology were used to detect karyotype and genome-wide copy number variation. Results: Of the 122 cases of fetal genetic results, 23 were abnormal results (18.85%, 23/122). 11 cases had abnormal karyotypes (9.02%, 11/122) ), 9 cases had aneuploidy (7.38%, 9/122), and 2 cases exhibited mosaicism (1.64%, 2/122). Chromosomal microarray analysis detected 12 cases (9.84%, 12/122) of CNVs. There were 6 cases of pCNV (4.92%, 6/122) and 6 cases of VOUS (4.92%, 6/122). CMA detected an additional 4.92% of pathogenic genetic abnormalities than karyotype analysis. The abnormal karyotype detection rate of the CHD group with extracardiac abnormalities was significantly higher than that of the independent CHD group (27.78% vs. 5.34%, P<0.01). The abnormal karyotype and pCNV detection rate of non-isolated ventricular septal defects were significantly higher than those of isolated ventricular septal defects, (23.53% vs. 0%, P<0.01; 14.71% vs. 0%). P < 0.05,). The detection rate of pCNV in the solitary ventricular septal defect with abnormal soft index group was significantly higher than that in the solitary ventricular septal defect group(36.4% vs. 0%, P<0.001). The detection rate of abnormal karyotype in the ventricular septal defect with extracardiac abnormality group was significantly higher than that in the isolated ventricular septal defect group (33.33% vs. 0%, P<0.05). Conclusion: Chromosomal microarray analysis technology can improve the detection rate of CHD in fetuses. CMA can detect 4.92% more pathogenic copy number variation than chromosomal karyotype analysis and the abnormal karyotype detection rate of CHD with extracardiac abnormalities was high. We observed a high detection rate of pathogenic CNV in non-isolated ventricular septal defect.