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

作者：Yu An, Wenyuan Duan, Guoying Huang, Xiaoli Chen, Li Li, Chenxia Nie, Jia Hou, Yonghao Gui, Yiming Wu, Feng Zhang, Yiping Shen, Bai-Lin Wu, Hongyan Wang · 发表于：BMC Medical Genomics · 年份：2015 · DOI：10.1186/s12920-015-0163-4 · 被引用次数：27 · 研究领域：Congenital heart defects research、Genomic variations and chromosomal abnormalities、Congenital Heart Disease Studies

BACKGROUND: Ventricular 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. METHODS: We 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. RESULTS: Among 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 als...