Application of a comprehensive subtelomere array in clinical diagnosis of mental retardation

K Kok*, T Dijkhuizen, YE Swart, H Zorgdrager, P van der Vlies, R Fehrmann, GJ te Meerman, KBJ Gerssen-Schoorl, T van Essen, B Sikkema-Raddatz, CHCM Buys

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

29 Citations (Scopus)

Abstract

In 2-8% of patients with mental retardation, small copy number changes in the subtelomeric region are thought to be the underlying cause. As detection of these genomic rearrangements is labour intensive using FISH, we constructed and validated a high-density BAC/PAC array covering the first 5 Mb of all subtelomeric regions and applied it in our routine screening of patients with idiopathic mental retardation for submicroscopic telomeric rearrangements. The present study shows the efficiency of this comprehensive subtelomere array in detecting terminal deletions and duplications but also small interstitial subtelomeric rearrangements, starting from small amounts of DNA. With our array, the size of the affected segments, at least those smaller than 5 Mb, can be determined simultaneously in the same experiment. In the first 100 patient samples analysed in our diagnostic practice by the use of this comprehensive telomere array, we found three patients with deletions in 3p, 10q and 15q, respectively, four patients with duplications in 9p, 12p, 21q and Xp, respectively, and one patient with a del 6q/dup 16q. The patients with del 3p and 10q and dup 12p had interstitial rearrangements that would have been missed with techniques using one probe per subtelomeric region chosen close to the telomere. (c) 2005 Elsevier SAS. All rights reserved.

Original languageEnglish
Pages (from-to)250-262
Number of pages13
JournalEuropean journal of medical genetics
Volume48
Issue number3
DOIs
Publication statusPublished - 2005

Keywords

  • array comparative genomic hybridisation
  • subtelomere array
  • subtelomeric rearrangements
  • mental retardation
  • multiple congenital anomalies
  • COMPARATIVE GENOMIC HYBRIDIZATION
  • PROBE AMPLIFICATION MLPA
  • REARRANGEMENTS
  • MICROARRAYS
  • DNA
  • IMBALANCES
  • DELETIONS
  • CHILDREN
  • CLONES

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