Division of Pediatric Cardiology, Department of Pediatrics and Child Health (N.A.S., T.F.S., T.A., J.L., G.C., R.D.D., L.S., A.J., L.J.Z.).
Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, United Kingdom (J.E., B.D.K.).
Circ Genom Precis Med. 2022 Dec;15(6):e003510. doi: 10.1161/CIRCGEN.121.003510. Epub 2022 Oct 7.
Congenital heart disease (CHD) is a leading non-infectious cause of pediatric morbidity and mortality worldwide. Although the etiology of CHD is poorly understood, genetic factors including copy number variants (CNVs) contribute to the risk of CHD in individuals of European ancestry. The presence of rare CNVs in African CHD populations is unknown. This study aimed to identify pathogenic and likely pathogenic CNVs in South African patients with CHD.
Genotyping was performed on 90 patients with nonsyndromic CHD using the Affymetrix CytoScan HD platform. These data were used to identify large, rare CNVs in known CHD-associated genes and candidate genes.
We identified eight CNVs overlapping known CHD-associated genes (, , , , , ) in six patients. The analysis also revealed CNVs encompassing five candidate genes likely to play a role in the development of CHD (, , , , ) in five patients. One patient was found to have 47, XXY karyotype. We report a total discovery yield of 6.7%, with 5.6% of the cohort carrying pathogenic or likely pathogenic CNVs expected to cause the observed phenotypes.
In this study, we show that chromosomal microarray is an effective technique for identifying CNVs in African patients diagnosed with CHD and have demonstrated results similar to previous CHD genetic studies in Europeans. Novel potential CHD genes were also identified, indicating the value of genetic studies of CHD in ancestrally diverse populations.
先天性心脏病（CHD）是全球导致儿童发病和死亡的主要非传染性病因。尽管 CHD 的病因尚不清楚，但包括拷贝数变异（CNVs）在内的遗传因素会增加欧洲血统个体患 CHD 的风险。非洲 CHD 人群中罕见 CNVs 的存在情况尚不清楚。本研究旨在鉴定南非 CHD 患者中存在的致病性和可能致病性的 CNVs。
使用 Affymetrix CytoScan HD 平台对 90 名非综合征性 CHD 患者进行基因分型。这些数据用于鉴定已知 CHD 相关基因和候选基因中的大型罕见 CNVs。
我们在 6 名患者中发现了 8 个与已知 CHD 相关基因（、、、、、）重叠的 CNVs。分析还揭示了 5 名患者中包含可能在 CHD 发生中发挥作用的候选基因（、、、、）的 CNVs。1 名患者被发现存在 47, XXY 染色体核型。我们报告总的检出率为 6.7%，其中 5.6%的患者携带致病性或可能致病性的 CNVs，预计会导致观察到的表型。
在这项研究中，我们表明染色体微阵列是一种有效的技术，可以鉴定被诊断为 CHD 的非洲患者中的 CNVs，其结果与欧洲先前的 CHD 遗传研究相似。还鉴定出了新的潜在 CHD 基因，这表明对具有不同祖先背景的 CHD 进行遗传研究具有价值。
