Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
BMC Med Genomics. 2021 Oct 9;14(1):243. doi: 10.1186/s12920-021-01090-y.
Congenital 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.
We 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.
Among 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.
Our 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.
先天性心脏病（CHD）是最常见的出生缺陷之一。已证实拷贝数变异（CNVs）是导致 CHD 的重要遗传因素。我们在此对患有完全性房室管缺损（CAVC）和单心室（SV）的中国儿童进行了全基因组 CNV 筛查，因为针对这两种 CHD 的研究很少。
我们分别使用定制的 SNP 芯片对 262 例散发性 CAVC 病例和 259 例散发性 SV 病例进行了 CNV 筛查。使用可用数据库对检测到的 CNVs 进行注释和过滤。
在 262 例 CAVC 患者中，我们在 43 名患者（16.41%，43/262）中发现了 6 个潜在致病 CNV，包括 2 个综合征相关 CNV（7q11.23 和 8q24.3 缺失）。令人惊讶的是，90.70%（39/43）携带 CNV 的 CAVC 患者存在 21q11.2-21q22.3 的重复，这被认为是 21 三体（唐氏综合征，DS）。在患有 DS 的 CAVC 患者中，女性与男性的比例为 1.6:1.0（24:15），肺动脉高压（PH）的发生率为 41.03%（16/39）。此外，我们在 SV 患者中发现了 6 个潜在致病 CNV（2.32%，6/259），其中没有一个是 21 三体。我们队列中大多数鉴定的 CNV 被归类为罕见（<1%），除了 CAVC 队列中 21q11.2-21q22.3 重复（14.89%）外，它们在 CAVC 或 SV 个体中仅发生一次。
我们在 262 例 CAVC 和 259 例 SV 患者中鉴定了 12 个潜在致病 CNV，这代表了中国人群中这两种 CHD 类型的最大队列。结果表明 CAVC 与 DS 之间存在很强的相关性，且具有性别差异和高 PH 发生率。潜在致病 CNV 的存在表明复杂 CHD 的病因极其多样化，CHD 的候选基因仍有待发现。
