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Detection of known and novel genomic rearrangements by array-CGH: deletion of ZNF533 and duplication of CHARGE syndrome genes
  1. Sandra Monfort (monmem{at}
  1. Hospital Universitario La Fe, Spain
    1. Monica Rosello (rosello_mpi{at}
    1. Hospital Universitario La Fe, Spain
      1. Carmen Orellana (orellana_car{at}
      1. Hospital Universitario La Fe, Spain
        1. Silvestre Oltra (jsoltra{at}
        1. Hospital Univesritario La Fe, Spain
          1. David Blesa (dblesa{at}
          1. Centro de Investigación Príncipe Felipe, CIPF, Spain
            1. Klaas Kok (k.kok{at}
            1. University Medical Centre Groningen, Netherlands
              1. Irene Ferrer (irenefbolufer{at}
              1. Hospital Universitario La Fe, Spain
                1. Juan C. Cigudosa (jccigudosa{at}
                1. Centro Nacional Investigaciones Oncológicas (CNIO), Spain
                  1. Francisco Martinez (francisco{at}
                  1. Hospital Universitario La Fe, Spain


                    PURPOSE: 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 hybridization allows to detect 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 6,465 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; while 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 were 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 most probably is the fourth zinc-finger gene implied in mental retardation. On the other hand, we propose that CHD7 gene, associated with CHARGE syndrome by haploinsufficiency, causes a different phenotype by gain-of-dosage.

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