Screening for Chromosomal Deletions and Duplications in Congenital Heart Disease using Multiplex Ligation-dependent Probe Amplification

  • Dr Milad El-Segaier, Department of Paediatric Cardiology, Lund University Hospital, Lund, Sweden, Sweden
  • Ms Karina Sørensen, Statens Serum Institut, Copenhagen, Denmark, Denmark
  • Dr Patrice Bouvagnet, Department of Pediatric Cardiology, Groupe Hospitalier Est, Lyon, France, France
  • Dr Jesper Stensbjerg, Department of Paediatric Cardiology, Copenhagen University Hospital, Copenhagen, Denmark, Denmark
  • Dr Ab Errami, MRC-Holland, Amsterdam, The Netherlands, The Netherlands
  • Dr Jan Schouten, MRC-Holland, Amsterdam, The Netherlands, The Netherlands
  • Dr Vibeke Hjortdal, Department of Cardiothoracic and Vascular Surgery, Skejby, Aarhus, Denmark, Denmark
  • Dr Lars Larsen, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark, Denmark

    • Objective: Recent studies have suggested that chromosomal deletions and duplications may be found in a proportion of patients with congenital heart disease (CHD).
    Methods: We have designed an assay for simultaneous analysis of deletions and duplications in 26 genomic regions which have previously been associated with CHD. The assay is based on the Multiplex Ligation-dependent Probe Amplification (MLPA) technique. The assay is performed in a single reaction and targets the following genomic regions: 1p36, 1q21, 2q37, 2p22, 3q22, 4q32, 4p16, 5q35.2, 5q35.3, 6p25.3, 7q22, 7q11.23, 8q12.2, 8p23.2, 8p23.1, 8q34.13, 8q34.11, 10q25.2, 10q25.3, 11q25, 13q14, 15q26, 17p13, 17p11, 20p12, 22q11.
    Results and conclusions: At the time of abstract submission we have screened 173 patients with CHD using the CHD-MLPA kit. The screening has revealed previously undetected chromosome abnormalities in eight patients; 22q11 duplication (4 patients), 22q11 deletion (one patient), 5q35 triplication (one patient), 2p22 duplication (one patient) and 2q37 deletion (one patient).

    Conclusion: Our data suggest that approximately 5% of patients with CHD are carriers of rare chromosomal abnormalities which can be easily detected using the current designed kit; CHD-MLPA.