J Med Genet 41:241-248 doi:10.1136/jmg.2003.017731
  • Original article

Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features

  1. C Shaw-Smith1,*,
  2. R Redon2,*,
  3. L Rickman1,*,
  4. M Rio3,
  5. L Willatt4,
  6. H Fiegler2,
  7. H Firth1,
  8. D Sanlaville3,
  9. R Winter5,
  10. L Colleaux3,
  11. M Bobrow1,
  12. N P Carter2
  1. 1University of Cambridge Department of Medical Genetics, Addenbrooke’s Hospital, Hills Road, Cambridge, UK
  2. 2The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK
  3. 3Département de Génétique and INSERM U393, Hôpital Necker-Enfants Malades, rue de Sèvres, Paris, France
  4. 4Regional Cytogenetics Laboratory, Addenbrooke’s Hospital, Cambridge
  5. 5Department of Clinical and Molecular Genetics, Institute of Child Health, London WC1, UK
  1. Correspondence to:
 Dr N P Carter
 The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK;
  • Accepted 18 January 2004
  • Revised 8 January 2004


The underlying causes of learning disability and dysmorphic features in many patients remain unidentified despite extensive investigation. Routine karyotype analysis is not sensitive enough to detect subtle chromosome rearrangements (less than 5 Mb). The presence of subtle DNA copy number changes was investigated by array-CGH in 50 patients with learning disability and dysmorphism, employing a DNA microarray constructed from large insert clones spaced at approximately 1 Mb intervals across the genome. Twelve copy number abnormalities were identified in 12 patients (24% of the total): seven deletions (six apparently de novo and one inherited from a phenotypically normal parent) and five duplications (one de novo and four inherited from phenotypically normal parents). Altered segments ranged in size from those involving a single clone to regions as large as 14 Mb. No recurrent deletion or duplication was identified within this cohort of patients. On the basis of these results, we anticipate that array-CGH will become a routine method of genome-wide screening for imbalanced rearrangements in children with learning disability.


  • * These three authors made an equal contribution to the work.

  • Conflicts of interest: none declared