Objective: In prenatal diagnosis, some polymalformed foetuses with suspicion of chromosomal abnormalities have normal standard karyotype. Routine chromosome analysis identifies structural rearrangements greater than 5 Mb but cannot identify abnormalities of the telomeric regions or microdeletions reliably. Molecular cytogenetic techniques were developed to overcome these limitations. BAC-based array comparative genomic hybridization array (CGH-array) were developed to increase the resolution of chromosomal studies and to provide a comprehensive assay by using large-insert clones as the target for analysis. We propose to use this technology to better understand the pathology in few foetuses with polymalformation syndrome and apparently balanced karyotype. Materials and methods: Comparative genomic hybridization has been used extensively to document gains and losses of genomic DNA in diseases such as cancer and mental retardation the development of CGH using arrays has improved the resolution of these analyses, allowing better detection. We used DNA microarrays (Genosystem®) according to their instruction. Abnormalities have been confirmed by Fish. Results: In three cases, this technology allowed us to correlate the abnormal phenotype with an imbalance chromosomal abnormality, (a tetrasomy 12p corresponding to a Pallister-Killian syndrome, a deletion of 7qter on derivative 10 of an inherited maternal reciprocal translocation t(7;10). In the third case, the prenatal caryotype of a foetus with holoprosencephaly showed a de novo apparently balanced reciprocal translocation t(7;8). By Fish, we identified an additional deletion in the region of the Sonic Hedgehog gene. Discussion and conclusion: We show the feasibility and the usefulness of CGH-array in constitutional cytogenetics. © 2007 Elsevier Masson SAS. All rights reserved.
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