Yu Xiafeng, Tao Yu, Liu Xu, Yu Feng, Jiang Chuan, Xiao Yingying, Zhang Haibo, He Yongrui, Ye Lincai, Wang Ying, Zhou Chunxia, Wang Jian, Jiang Zhengwen, Hong Haifa
Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Genetics, Genesky Biotechnologies Inc., Shanghai, China.
Front Cardiovasc Med. 2023 May 24;10:1164577. doi: 10.3389/fcvm.2023.1164577. eCollection 2023.
Copy 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.
CNVs 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.
We 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%; = 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%, < 0.001). Duration of cardiopulmonary bypass and aortic cross clamp procedures were significantly longer in CHD cases with ppCNVs (all < 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%, = 0.002).
CNV 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.
拷贝数变异（CNV）在先天性心脏病（CHD）患儿中表现出过高的比例。目前中国对CHD的基因评估开展不足。我们试图确定一大群中国儿科CHD患者中具有致病潜力的CNV区域内CNV的发生率，并研究这些CNV是否可能是手术干预的重要关键修饰因子。
对1762名至少接受过一次心脏手术的中国儿童进行CNV筛查。采用高通量连接依赖探针扩增（HLPA）分析法分析200多个具有致病潜力的CNV位点的CNV状态。
我们发现1762个样本中有378个（21.45%）至少有一个CNV，其中2.38%携带多个CNV。致病性和可能致病性CNV（ppCNV）的检出率为9.19%（162/1762），显著高于基因组变异数据库存档中的健康汉族个体（9.19%对3.63%；P = 0.0012）。与无ppCNV的CHD患者相比，有ppCNV的CHD病例进行复杂手术的比例显著更高（62.35%对37.63%，P < 0.001）。有ppCNV的CHD病例体外循环和主动脉阻断时间显著更长（均P < 0.05），而手术并发症和术后1个月死亡率在两组间无差异。房室间隔缺损（AVSD）亚组中ppCNV的检出率显著高于其他亚组（23.10%对9.70%，P = 0.002）。
CNV负荷是中国CHD患儿的一个重要因素。我们的研究证明了HLPA方法在CHD患者CNV基因筛查中的稳健性和诊断效率。
