title: No evidence for mosaic pathogenic copy number variations in cardiac tissue from patients with congenital heart malformations.
abstract: 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.
authors: Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: johanna.winberg@ki.se.
authors: Johanna
authors: J
authors: Winberg
authors: Pediatric Cardiac Surgery Unit, Queen Silvia Children's Hospital, Gothenburg, Sweden.
authors: Håkan
authors: H
authors: Berggren
authors: Pediatric Cardiac Surgery Unit, Children's Hospital, University Hospital, Lund, Sweden.
authors: Torsten
authors: T
authors: Malm
authors: Pediatric Cardiac Surgery Unit, Children's Hospital, University Hospital, Lund, Sweden.
authors: Sune
authors: S
authors: Johansson
authors: Pediatric Cardiac Surgery Unit, Children's Hospital, University Hospital, Lund, Sweden.
authors: Jens
authors: J
authors: Johansson Ramgren
authors: Pediatric Cardiac Surgery Unit, Queen Silvia Children's Hospital, Gothenburg, Sweden.
authors: Boris
authors: B
authors: Nilsson
authors: Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Agne
authors: A
authors: Liedén
authors: Department of Woman and Child Health and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Pediatric Surgery, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
authors: Agneta
authors: A
authors: Nordenskjöld
authors: Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Peter
authors: P
authors: Gustavsson
authors: Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Ann
authors: A
authors: Nordgren
mesh_terms: D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009030:Mosaicism
keywords: Array CGH; Congenital heart malformations; Copy number variation; Mosaicism