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Detection of known and novel genomic rearrangements by array based comparative genomic hybridisation: deletion of ZNF533 and duplication of CHARGE syndrome genes
  1. S Monfort1,
  2. M Roselló1,
  3. C Orellana1,
  4. S Oltra1,
  5. D Blesa2,
  6. K Kok3,
  7. I Ferrer1,
  8. J C Cigudosa4,
  9. F Martínez1
  1. 1
    Unidad de Genética y Diagnóstico Prenatal, Hospital Universitario La Fe, Valencia, Spain
  2. 2
    Servicio de Análisis de Microarrays, Centro de Investigación Príncipe Felipe, CIPF, Valencia, Spain
  3. 3
    Department of Medical Genetics, University Medical Centre Groningen and University of Groningen, Groningen, The Netherlands
  4. 4
    Molecular Cytogenetics Group, Centro Nacional de Investigaciones Oncológicas (CNIO), and CIBER on Rare Diseases (CIBERER), Madrid, Spain
  1. Dr F Martínez, Unidad de Genética y Diagnóstico Prenatal, Hospital Universitario La Fe. Avenida Campanar, 21. 46009 Valencia, Spain; francisco{at}


Background: Mental retardation can be caused by copy number variations (deletions, insertions, duplications), ranging in size from 1 kb to several megabases. Array based comparative genomic hybridisation (array-CGH) allows detection of an increasing number of genomic alterations.

Methods: A series of 46 patients with mental retardation and congenital abnormalities (previously screened for subtelomeric rearrangements) were evaluated for cryptic chromosomal imbalances by array-CGH. This array contains 6465 large-insert BAC/PAC clones, representing sequences uniformly distributed throughout the human genome. The results were confirmed by alternative techniques.

Results: Four pathogenic rearrangements were detected: two of them were novel, a deletion at 2q31.2 and a duplication at 8q12 band; the other two have been previously reported—a duplication of the Williams–Beuren region and a deletion of 3q29. By adding the subtelomeric alterations previously identified, a total rate of 18% of pathogenic rearrangements was found in the series.

Conclusion: Based on our results, ZNF533 is the only gene contained in the overlapping region with other deletions at 2q31.2, and it is most probably the fourth zinc-finger gene implied in mental retardation. On the other hand, we propose that the CHD7 gene, associated with CHARGE syndrome by haploinsufficiency, causes a different phenotype by gain-of-dosage.

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  • Competing interests: None declared.

  • Patient consent: Informed consent was obtained for publication of the details of all the patients described in this article.