BioProject

Tetralogy of Fallot (TOF), the most frequent cyanotic congenital heart disease, occurs as a simplex trait of unknown etiology in the majority of cases. More...

Tetralogy of Fallot (TOF), the most frequent cyanotic congenital heart disease, occurs as a simplex trait of unknown etiology in the majority of cases. Studies of non-Asian populations suggest that approximately 10% of TOF cases carry a de novo rare copy number variant (CNV) thought to underlie the malformation. A genome-wide CNV analysis was performed in 303 TOF and 302 controls of Han Chinese as well as compared to 1,000 common Chinese database and revealed 166 rare CNVs identified in TOF patients with 119 CNVs further evaluated as potential “TOF-specific CNVs”; 98 were validated by qPCR, and 44 CNVs showed positive results on validation (positive rate 46.9%, 44/98). The genes related to the clinical phenotypes (subpulmonary VSD, bicuspid pulmonary valve, aortic valve overriding more than 75%, and right aortic arch) and the specific CNVs were included in integrating gene-gene interaction network analysis that identified the genes covering the specific CNVs directly or indirectly correlated to TOF and the signaling pathways. Thus, this study identified novel TOF-specific/associate CNVs in the Han Chinese that occurring at higher frequency in the Han Chinese (28.4% in Chr 1-20 and 42.9% in all chromosomes) is reflective of the increased prevalence of TOF in China. These novel CNVs identify new candidate genes for TOF. Our findings provide new insight into the contribution of CNVs to the genetic basis of TOF and identify new genetic loci potentially important to the pathogenesis of TOF Overall design: A total of 303 isolated TOF patients and 302 normal control subjects (Control-1) were recruited (the first batch of 466 samples is included in the current records). An informed consent form was obtained from their parents or guardians. All TOF patients were Chinese children from TEDA International Cardiovascular Hospital and associated hospitals（Guangzhou Women and Children Medical Center and Qingdao Children’s Hospital. Age-matched control subjects (between 2 month to 15 years) were assembled from healthy children or children without congenital or cardiac disease. The project was approved by the Institutional Review Board (Ethics Committee) of TEDA International Cardiovascular Hospital. Informed consent was obtained from all subjects or their guardians. A diagnosis of TOF was made with echocardiography or echocardiography plus catheterization, MRI, or CT scan and was confirmed in corrective cardiac surgery. Clinical records were reviewed before recruitment. Less...