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This Article Full Text Full Text (PDF) web only appendices All Versions of this Article: jmg.2008.057596v1 45/7/432    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Google Scholar Articles by Monfort, S Articles by Martínez, F PubMed PubMed Citation Articles by Monfort, S Articles by Martínez, F

Detection of known and novel genomic rearrangements by array based comparative genomic hybridisation: deletion of ZNF533 and duplication of CHARGE syndrome genes

¹ Unidad de Genética y Diagnóstico Prenatal, Hospital Universitario La Fe, Valencia, Spain
² Servicio de Análisis de Microarrays, Centro de Investigación Príncipe Felipe, CIPF, Valencia, Spain
³ Department of Medical Genetics, University Medical Centre Groningen and University of Groningen, Groningen, The Netherlands
⁴ Molecular Cytogenetics Group, Centro Nacional de Investigaciones Oncológicas (CNIO), and CIBER on Rare Diseases (CIBERER), Madrid, Spain

Correspondence to:
Dr F Martínez, Unidad de Genética y Diagnóstico Prenatal, Hospital Universitario La Fe. Avenida Campanar, 21. 46009 Valencia, Spain; francisco{at}gva.es]

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.