Datasheet2_The implication of chromosomal abnormalities in the surgical outcomes of Chinese pediatric patients with congenital heart disease.pdf

BackgroundCopy number variations (CNVs) have been shown to be overrepresented in children with congenital heart disease (CHD). Genetic evaluation of CHD is currently underperformed in China. We sought to determine the occurrence of CNVs in CNV regions with disease-causing potential among a large cohort of Chinese pediatric CHD patients and investigate whether these CNVs could be the important critical modifiers of surgical intervention.
MethodsCNVs screenings were performed in 1,762 Chinese children who underwent at least one cardiac surgery. CNV status at over 200 CNV locus with disease-causing potential was analyzed with a high-throughput ligation-dependent probe amplification (HLPA) assay.
ResultsWe found 378 out of 1,762 samples (21.45%) to have at least one CNV and 2.38% of them were carrying multiple CNVs. The detection rates of ppCNVs (pathogenic and likely pathogenic CNVs) were 9.19% (162/1,762), significantly higher than that of the healthy Han Chinese individuals from The Database of Genomic Variants archive (9.19% vs. 3.63%; P = 0.0012). CHD cases with ppCNVs had a significantly higher proportion of complex surgeries compared to CHD patients with no ppCNVs (62.35% vs. 37.63%, P < 0.001). Duration of cardiopulmonary bypass and aortic cross clamp procedures were significantly longer in CHD cases with ppCNVs (all P < 0.05), while no group differences were identified for complications of surgery and one-month mortality after surgery. The detection rate of ppCNVs in the atrioventricular septal defect (AVSD) subgroup was significantly higher than that in other subgroups (23.10% vs. 9.70%, P = 0.002).
ConclusionsCNV burden is an important contributor to Chinese children with CHD. Our study demonstrated the robustness and diagnostic efficiency of HLPA method in the genetic screening of CNVs in CHD patients.

研究背景：已有研究证实，拷贝数变异（Copy number variations, CNVs）在先天性心脏病（congenital heart disease, CHD）儿童群体中检出率显著升高。目前我国先天性心脏病的遗传评估开展仍不足。本研究旨在明确中国大型儿童先天性心脏病队列中，具有致病潜力的拷贝数变异区域内拷贝数变异的发生情况，并探讨此类拷贝数变异是否可作为手术干预的重要关键修饰因子。
研究方法：本研究对1762名接受过至少1次心脏手术的中国儿童开展拷贝数变异筛查。采用高通量连接依赖性探针扩增（high-throughput ligation-dependent probe amplification, HLPA）技术，对200余个具有致病潜力的拷贝数变异位点进行拷贝数状态分析。
研究结果：1762例样本中，378例（21.45%）检出至少1种拷贝数变异，其中2.38%的个体携带多种拷贝数变异。致病性及可能致病性拷贝数变异（pathogenic and likely pathogenic CNVs, ppCNVs）的检出率为9.19%（162/1762），显著高于基因组变异数据库存档中健康汉族个体的检出率（9.19% vs. 3.63%；P=0.0012）。与未检出致病性及可能致病性拷贝数变异的先天性心脏病患者相比，携带此类变异的患者接受复杂心脏手术的比例显著更高（62.35% vs. 37.63%，P<0.001）。携带致病性及可能致病性拷贝数变异的先天性心脏病患者，其体外循环时长与主动脉阻断术时长均显著更长（均P<0.05）；但两组患者的手术并发症发生率与术后1个月死亡率无显著组间差异。房室间隔缺损（atrioventricular septal defect, AVSD）亚组的致病性及可能致病性拷贝数变异检出率显著高于其他亚组（23.10% vs. 9.70%，P=0.002）。
研究结论：拷贝数变异负荷是中国儿童先天性心脏病的重要致病因素。本研究证实了高通量连接依赖性探针扩增技术在先天性心脏病患者拷贝数变异遗传筛查中的稳定性与诊断效能。