Mate pair sequencing for the detection of chromosomal aberrations in patients with intellectual disability and congenital malformations

Sarah Vergult, Ellen Van Binsbergen, Tom Sante, Silke Nowak, Olivier Vanakker, Kathleen Claes, Bruce Poppe, Nathalie Van der Aa, Markus J van Roosmalen, Karen Duran, Masoumeh Tavakoli-Yaraki, Marielle Swinkels, Marie-José van den Boogaard, Mieke van Haelst, Filip Roelens, Frank Speleman, Edwin Cuppen, Geert Mortier, Wigard P Kloosterman, Björn Menten

Research output: Contribution to journalArticleAcademicpeer-review

26 Citations (Scopus)


Recently, microarrays have replaced karyotyping as a first tier test in patients with idiopathic intellectual disability and/or multiple congenital abnormalities (ID/MCA) in many laboratories. Although in about 14-18% of such patients, DNA copy-number variants (CNVs) with clinical significance can be detected, microarrays have the disadvantage of missing balanced rearrangements, as well as providing no information about the genomic architecture of structural variants (SVs) like duplications and complex rearrangements. Such information could possibly lead to a better interpretation of the clinical significance of the SV. In this study, the clinical use of mate pair next-generation sequencing was evaluated for the detection and further characterization of structural variants within the genomes of 50 ID/MCA patients. Thirty of these patients carried a chromosomal aberration that was previously detected by array CGH or karyotyping and suspected to be pathogenic. In the remaining 20 patients no causal SVs were found and only benign aberrations were detected by conventional techniques. Combined cluster and coverage analysis of the mate pair data allowed precise breakpoint detection and further refinement of previously identified balanced and (complex) unbalanced aberrations, pinpointing the causal gene for some patients. We conclude that mate pair sequencing is a powerful technology that can provide rapid and unequivocal characterization of unbalanced and balanced SVs in patient genomes and can be essential for the clinical interpretation of some SVs.

Original languageEnglish
Pages (from-to)652-9
Number of pages8
JournalEuropean journal of human genetics
Issue number5
Publication statusPublished - May 2014


  • Abnormalities, Multiple/diagnosis
  • Chromosome Aberrations
  • Chromosome Banding
  • Chromosome Duplication
  • Chromosomes, Human, Pair 18
  • Chromosomes, Human, Pair 21
  • Comparative Genomic Hybridization
  • Computational Biology
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Intellectual Disability/diagnosis
  • Karyotype
  • Male
  • Recombination, Genetic

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