Diagnostic value of CMA in different phenotypes of fetal congenital heart defects

Abstract Objective To evaluate the detection rate of fetal chromosomal abnormalities in congenital heart defects (CHD), further dig the potential diagnostic value of Chromosomal Microarray Analysis (CMA) technology for different phenotypes, and explore the possible genetic pathogenic factors of CHD. Methods We analyzed the CMA of 427 cases of CHD fetuses, and divided CHD into different groups according to two dimensions. According to whether they were combined with ECA, they were divided into isolated CHD and non-isolated CHD; According to the cardiac phenotype, they were divided into ten groups. The correlation between numerical chromosomal abnormalities (NCA), and copy number variations (CNVs, except likely benign and benign CNVs) with CHD was analyzed by Mantel test. Results In general, CHD with ECAs were more likely to have a genetic abnormality than those without ECAs (39.3% vs. 14.8%, P <0.05). The genetic abnormality rate of 427 fetuses was 21.8% (93/427), the detection rate of NCA was 12.9% (55/427), the most relevant were skeletal, Craniofacial, VSD, AVSD (P<0.05); and the detection rate of pCNVs was 8.9% (38/427), the most relevant were IAA, A, IAA, B, RAA, TAPVC, CoA, TOF and thymic abnormality. 22q11.2DS and had the highest detection, the detection rate of 22q11.2DS in the subgroups were IAA, B, RAA, PS, CoA, TOF and thymic abnormality. Overall analysis of cases, the CNV deletion fragment larger than 1 Mb may be pathogenic. In CNV, deletion was more likely to be pathogenic than duplication. In addition, we detected 12 CNV syndromes; among of them, 9 syndromes that may be related to CHD. gene LIMK1 and MYH11 have been identified as part of a common pathway between cardiovascular and neurological development; candidate genes are considered to be related to heart and/or involved in embryonic development, FLI1, NIPBL, DLL1, PTPN11, TBX5. Conclusion Increased risk of genetic abnormalities in non-isolated CHD; CHD phenotype most related to NCA, pCNV and 22q11.2DS was found; and 12 CNV syndromes and 7 meaningful candidate genes were detected.