How to Cite this Article: Sørensen KM, El-Segaier M, Fernlund E, Errami A, Bouvagnet P, Nehme N, Steensberg J, Hjortdal V, Soller M, Behjati M, Werge T, Kirchoff M, Schouten J, Tommerup N, Andersen PS, Larsen LA. 2012. Screening of congenital heart disease patients using multiplex ligation-dependent probe amplification: Early diagnosis of syndromic patients. Am J Med Genet Part A 158A:720–725.
Screening of congenital heart disease patients using multiplex ligation-dependent probe amplification: Early diagnosis of syndromic patients†
Article first published online: 1 MAR 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 4, pages 720–725, April 2012
How to Cite
Sørensen, K. M., El-Segaier, M., Fernlund, E., Errami, A., Bouvagnet, P., Nehme, N., Steensberg, J., Hjortdal, V., Soller, M., Behjati, M., Werge, T., Kirchoff, M., Schouten, J., Tommerup, N., Andersen, P. S. and Larsen, L. A. (2012), Screening of congenital heart disease patients using multiplex ligation-dependent probe amplification: Early diagnosis of syndromic patients. Am. J. Med. Genet., 158A: 720–725. doi: 10.1002/ajmg.a.35214
- Issue published online: 23 MAR 2012
- Article first published online: 1 MAR 2012
- Manuscript Accepted: 10 NOV 2011
- Manuscript Received: 28 APR 2011
- SAFE Network of Excellence (EC Contract No LSHB-CT-2004-5053243)
- Danish Heart Foundation
- Novo Nordisk Foundation
- congenital heart disease;
- multiplex ligation-dependent probe amplification;
- copy number variants, CNVs
Recurrent copy number variants (CNVs) are found in a significant proportion of patients with congenital heart disease (CHD) and some of these CNVs are associated with other developmental defects. In some syndromic patients, CHD may be the first presenting symptom, thus screening of patients with CHD for CNVs in specific genomic regions may lead to early diagnosis and awareness of extracardiac symptoms. We designed a multiplex ligation-dependent probe amplification (MLPA) assay specifically for screening of CHD patients. The MLPA assay allows for simultaneous analysis of CNVs in 25 genomic regions previously associated with CHD. We screened blood samples from 402 CHD patients and identified 14 rare CNVs in 13 (3.2%) patients. Five CNVs were de novo and six where inherited from a healthy parent. The MLPA screen led to early syndrome diagnosis in two of these patients. We conclude that the MLPA assay detects clinically relevant CNVs and suggest that it could be used within pediatric cardiology as a first tier screen to detect clinically relevant CNVs and identify syndromic patients at an early stage. © 2012 Wiley Periodicals, Inc.