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Chromosomal copy number changes in patients with non-syndromic X linked mental retardation detected by array CGH
  1. D Lugtenberg1,
  2. A P M de Brouwer1,
  3. T Kleefstra1,
  4. A R Oudakker1,
  5. S G M Frints2,
  6. C T R M Schrander-Stumpel2,
  7. J P Fryns3,
  8. L R Jensen4,
  9. J Chelly5,
  10. C Moraine6,
  11. G Turner7,
  12. J A Veltman1,
  13. B C J Hamel1,
  14. B B A de Vries1,
  15. H van Bokhoven1,
  16. H G Yntema1
  1. 1Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  2. 2Department of Clinical Genetics, University Hospital Maastricht, Maastricht, The Netherlands
  3. 3Center for Human Genetics, University of Leuven, Leuven, Belgium
  4. 4Max Planck Institute for Molecular Genetics, Berlin, Germany
  5. 5INSERM 129-ICGM, Faculté de Médecine Cochin, Paris, France
  6. 6Service de Génétique et INSERM U316, Hôpital Bretonneau, Tours, France
  7. 7GOLD Program, Hunter Genetics, University of Newcastle, Callaghan, NSW, Australia
  1. Correspondence to:
 Helger G Yntema
 PhD, Department of Human Genetics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; h.yntema{at}


Several studies have shown that array based comparative genomic hybridisation (CGH) is a powerful tool for the detection of copy number changes in the genome of individuals with a congenital disorder. In this study, 40 patients with non-specific X linked mental retardation were analysed with full coverage, X chromosomal, bacterial artificial chromosome arrays. Copy number changes were validated by multiplex ligation dependent probe amplification as a fast method to detect duplications and deletions in patient and control DNA. This approach has the capacity to detect copy number changes as small as 100 kb. We identified three causative duplications: one family with a 7 Mb duplication in Xp22.2 and two families with a 500 kb duplication in Xq28 encompassing the MECP2 gene. In addition, we detected four regions with copy number changes that were frequently identified in our group of patients and therefore most likely represent genomic polymorphisms. These results confirm the power of array CGH as a diagnostic tool, but also emphasise the necessity to perform proper validation experiments by an independent technique.

  • BAC, bacterial artificial chromosome
  • CGH, comparative genomic hybridisation
  • CNP, copy number polymorphism
  • FISH, fluorescent in situ hybridisation
  • FSIQ, full scale intelligence quotient
  • MLPA, multiplex ligated probe amplification
  • MR, mental retardation
  • MRX, non-syndromic X linked mental retardation
  • MRXS, syndromic X linked mental retardation
  • STS, sequence tagged site
  • T/R, test over reference
  • XLMR, X linked mental retardation
  • Array CGH
  • XLMR
  • duplications
  • copy number polymorphisms (CNPs)
  • MLPA

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  • Published Online First 16 September 2005

  • Competing interests: there are no competing interests.

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