Winberg Johanna, Berggren Håkan, Malm Torsten, Johansson Sune, Johansson Ramgren Jens, Nilsson Boris, Liedén Agne, Nordenskjöld Agneta, Gustavsson Peter, Nordgren Ann
Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Pediatric Cardiac Surgery Unit, Queen Silvia Children's Hospital, Gothenburg, Sweden.
Eur J Med Genet. 2015 Mar;58(3):129-33. doi: 10.1016/j.ejmg.2015.01.003. Epub 2015 Jan 31.
The aim of this study was to investigate if pathogenic copy number variations (CNVs) are present in mosaic form in patients with congenital heart malformations. We have collected cardiac tissue and blood samples from 23 patients with congenital heart malformations that underwent cardiac surgery and screened for mosaic gene dose alterations restricted to cardiac tissue using array comparative genomic hybridization (array CGH). We did not find evidence of CNVs in mosaic form after array CGH analysis. Pathogenic CNVs that were present in both cardiac tissue and blood were detected in 2/23 patients (9%), and in addition we found several constitutional CNVs of unclear clinical significance. This is the first study investigating mosaicism for CNVs in heart tissue compared to peripheral blood and the results do not indicate that pathogenic mosaic copy number changes are common in patients with heart malformations. Importantly, in line with previous studies, our results show that constitutional pathogenic CNVs are important factors contributing to congenital heart malformations.
本研究的目的是调查先天性心脏畸形患者中是否存在镶嵌形式的致病性拷贝数变异（CNV）。我们收集了23例接受心脏手术的先天性心脏畸形患者的心脏组织和血液样本，并使用阵列比较基因组杂交（array CGH）筛选仅限于心脏组织的镶嵌基因剂量改变。阵列CGH分析后，我们未发现镶嵌形式的CNV证据。在2/23例患者（9%）中检测到心脏组织和血液中均存在的致病性CNV，此外，我们还发现了几个临床意义不明确的染色体组CNV。这是第一项比较心脏组织与外周血中CNV镶嵌现象的研究，结果表明致病性镶嵌拷贝数变化在心脏畸形患者中并不常见。重要的是，与先前的研究一致，我们的结果表明，染色体组致病性CNV是导致先天性心脏畸形的重要因素。
