Abstract
BackgroundCongenital heart disease (CHD) is one of the most common birth defects. Copy number variations (CNVs) have been proved to be important genetic factors that contribute to CHD. Here we screened genome-wide CNVs in Chinese children with complete atrioventricular canal (CAVC) and single ventricle (SV), since there were scarce researches dedicated to these two types of CHD.MethodsWe screened CNVs in 262 sporadic CAVC cases and 259 sporadic SV cases respectively, using a customized SNP array. The detected CNVs were annotated and filtered using available databases.ResultsAmong 262 CAVC patients, we identified 6 potentially-causative CNVs in 43 individuals (16.41%, 43/262), including 2 syndrome-related CNVs (7q11.23 and 8q24.3 deletion). Surprisingly, 90.70% CAVC patients with detected CNVs (39/43) were found to carry duplications of 21q11.2–21q22.3, which were recognized as trisomy 21 (Down syndrome, DS). In CAVC with DS patients, the female to male ratio was 1.6:1.0 (24:15), and the rate of pulmonary hypertension (PH) was 41.03% (16/39). Additionally, 6 potentially-causative CNVs were identified in the SV patients (2.32%, 6/259), and none of them was trisomy 21. Most CNVs identified in our cohort were classified as rare (< 1%), occurring just once among CAVC or SV individuals except the 21q11.2–21q22.3 duplication (14.89%) in CAVC cohort.ConclusionsOur study identified 12 potentially-causative CNVs in 262 CAVC and 259 SV patients, representing the largest cohort of these two CHD types in Chinese population. The results provided strong correlation between CAVC and DS, which also showed sex difference and high incidence of PH. The presence of potentially-causative CNVs suggests the etiology of complex CHD is incredibly diverse, and CHD candidate genes remain to be discovered.
Highlights
Congenital heart disease (CHD) is one of the most common birth defects
Due to disrupted early-stage development, CHD consists of many structural malformations of the cardiovascular system, ranging from simple lesions such as atrial septal defects (ASD) and ventricular septal defects (VSD), to complex lesions such as tetralogy of Fallot (ToF), complete atrioventricular canal (CAVC) and single ventricle (SV)
Among the rest 521 samples (262 CAVC and 259 SV) who passed the QC tests, a total of 3465 Copy number variations (CNVs) were detected with a median size of 922.3 kb
Summary
Congenital heart disease (CHD) is one of the most common birth defects. We screened genome-wide CNVs in Chinese children with complete atrioventricular canal (CAVC) and single ventricle (SV), since there were scarce researches dedicated to these two types of CHD. Congenital heart disease (CHD) is the most common birth defect with an incidence of 1–1.2% in live births [1, 2]. Due to disrupted early-stage development, CHD consists of many structural malformations of the cardiovascular system, ranging from simple lesions such as atrial septal defects (ASD) and ventricular septal defects (VSD), to complex lesions such as tetralogy of Fallot (ToF), complete atrioventricular canal (CAVC) and single ventricle (SV). Consistent with the complexity of early heart development, the etiology of CHD is multifactorial. The evidences emphasize that genetics plays an important role in the pathogenesis of CHD [11]
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