Genome-wide copy number variant analysis for congenital ventricular septal defects in Chinese Han population

Abstract

BackgroundVentricular septal defects (VSDs) constitute the most prevalent congenital heart disease (CHD), occurs either in isolation (isolated VSD) or in combination with other cardiac defects (complex VSD). Copy number variation (CNV) has been highlighted as a possible contributing factor to the etiology of many congenital diseases. However, little is known concerning the involvement of CNVs in either isolated or complex VSDs.MethodsWe analyzed 154 unrelated Chinese individuals with VSD by chromosomal microarray analysis. The subjects were recruited from four hospitals across China. Each case underwent clinical assessment to define the type of VSD, either isolated or complex VSD. CNVs detected were categorized into syndrom related CNVs, recurrent CNVs and rare CNVs. Genes encompassed by the CNVs were analyzed using enrichment and pathway analysis.ResultsAmong 154 probands, we identified 29 rare CNVs in 26 VSD patients (16.9 %, 26/154) and 8 syndrome-related CNVs in 8 VSD patients (5.2 %, 8/154). 12 of the detected 29 rare CNVs (41.3 %) were recurrently reported in DECIPHER or ISCA database as associated with either VSD or general heart disease. Fifteen genes (5 %, 15/285) within CNVs were associated with a broad spectrum of complicated CHD. Among these15 genes, 7 genes were in “abnormal interventricular septum morphology” derived from the MGI (mouse genome informatics) database, and nine genes were associated with cardiovascular system development (GO:0072538).We also found that these VSD-related candidate genes are enriched in chromatin binding and transcription regulation, which are the biological processes underlying heart development.ConclusionsOur study demonstrates the potential clinical diagnostic utility of genomic imbalance profiling in VSD patients. Additionally, gene enrichment and pathway analysis helped us to implicate VSD related candidate genes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-015-0163-4) contains supplementary material, which is available to authorized users.

Prematurity, ventricular septal defect and dysmorphisms are independent predictors of pathogenic copy number variants: a retrospective study on array-CGH results and phenotypical features of 293 children with neurodevelopmental disorders and/or multiple congenital anomalies

“…In our study, VSD assumed an independent predictive value for pathogenic CNVs. This data appears to be supported by recent literature, which reports significant CNVs in 16.9% of patients with VSD [ 28 ].…”

Comparison of a teratogenic transcriptome-based predictive test based on human embryonic versus inducible pluripotent stem cells

“…Gain of function studies in chicken demonstrate that CLDN10 is crucial for normal heart tube looping [32]. The Protein Kinase C Beta ( PRKCB ) is also upregulated by VPA, and recently, significant copy number variation has been found in human patients with ventricular septal defects [33]. In accordance with our findings, it has been established that VPA stimulates PRKCB in several cell types [34, 35].…”

What have we learned from 691 prenatal chromosomal microarrays for ventricular septal defects?

“…Of these, seven full‐paper articles were retrieved as potentially suitable. We excluded papers that did not report the rates of microarray anomalies in isolated VSD but rather described CMA results in isolated vs non‐isolated VSD, a study that included one VSD pregnancy and manuscript that examined postnatal VSD cases . Thus, we found only four papers describing microarray testing results in isolated fetal VSD (Table ).…”