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Open Access Research article

Gene expression in cardiac tissues from infants with idiopathic conotruncal defects

Douglas C Bittel1*, Merlin G Butler2, Nataliya Kibiryeva1, Jennifer A Marshall3, Jie Chen4, Gary K Lofland3 and James E O'Brien3

Author Affiliations

1 Section of Medical Genetics and Molecular Medicine, Children's Mercy Hospitals and Clinics and University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA

2 Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas, Medical Center, Kansas City, KS, USA

3 Section of Cardiovascular and Thoracic Surgery, Children's Mercy Hospitals and Clinics and University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA

4 Department of Mathematics and Statistics, University of Missouri-Kansas City, Kansas City, MO, USA

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BMC Medical Genomics 2011, 4:1  doi:10.1186/1755-8794-4-1

Published: 5 January 2011

Abstract

Background

Tetralogy of Fallot (TOF) is the most commonly observed conotruncal congenital heart defect. Treatment of these patients has evolved dramatically in the last few decades, yet a genetic explanation is lacking for the failure of cardiac development for the majority of children with TOF. Our goal was to perform genome wide analyses and characterize expression patterns in cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery) obtained at the time of reconstructive surgery from 19 children with tetralogy of Fallot.

Methods

We employed genome wide gene expression microarrays to characterize cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery) obtained at the time of reconstructive surgery from 19 children with TOF (16 idiopathic and three with 22q11.2 deletions) and compared gene expression patterns to normally developing subjects.

Results

We detected a signal from approximately 26,000 probes reflecting expression from about half of all genes, ranging from 35% to 49% of array probes in the three tissues. More than 1,000 genes had a 2-fold change in expression in the right ventricle (RV) of children with TOF as compared to the RV from matched control infants. Most of these genes were involved in compensatory functions (e.g., hypertrophy, cardiac fibrosis and cardiac dilation). However, two canonical pathways involved in spatial and temporal cell differentiation (WNT, p = 0.017 and Notch, p = 0.003) appeared to be generally suppressed.

Conclusions

The suppression of developmental networks may represent a remnant of a broad malfunction of regulatory pathways leading to inaccurate boundary formation and improper structural development in the embryonic heart. We suggest that small tissue specific genomic and/or epigenetic fluctuations could be cumulative, leading to regulatory network disruption and failure of proper cardiac development.