Analysis of genomic copy number variations in 36 fetuses with heart malformations using next-generation sequencing

Abstract

To explore the implications of copy number variations (CNVs) for congenital heart diseases (CHD) in fetuses. G-banding karyotype analysis and next-generation sequencing (NGS) technology were performed on cord blood samples derived from 36 fetuses with CHD. Pathological implication of the CNVs was explored through comparison against the International Genomic Polymorphism Database (http://www.ebi.ac.uk/dgva/), Phenotype Database (http://decipher.sanger.ac.uk/), and the Human Genome Database at UCSC (http://genome.ucsc.edu/cgi-bin/hgGateway). G-banding karyotype analysis has identified 7 chromosomal abnormalities. For the remaining 28 cases, NGS has identified 4 microdeletions and microduplications, which involved chromosomes 2, 13, 14, 16 and 22. The largest involved a 6.8 Mb microdeletion, while the smallest involved a 280 kb microduplication. The chromosomal breakpoints in 1 case were delineated. One case of Noonan syndrome and one case of 22q11.2 deletion were diagnosed. NGS can accurately determine the origins of derivative chromosomes and facilitate identification of pathogenic CNVs/genes. It can serve as a useful complement for conventional G-banding and reduce the recurrence risk.