Our laboratory is accredited for this study. We regularly and successfully carry out full external validation studies (ring-trials).Due to the requirements of the KBV, Chapter 11.4 EBM, we ask you for array CGH requirements (using Laboratory referral form 10), make sure to cite the indication criteria according to EBM 11500 (additional sheet with explanation). Thank you.
For clarification of genomic imbalances in patients with unclear malformation/ retardation syndromes, we offer a high-resolution array CGH analysis.
The conventional chromosome analysis can detect structural chromosome aberrations with a size of about 5-10 million base pairs. Many disease-causing changes, microdeletions or duplications, are in their extension below the resolution limit of the chromosome analysis and are not detected by this method. The subtelomere analysis determines only about 2.5% of the malformation/ retardation syndrome cases (Ravnan et al. J Med Genet 2006).
In recent years, the genome research has enabled the production of gene chips, so-called microarrays. This technique very commonly used is the comparative genomic hybridization (CGH). The DNA of the subject is labeled with one dye and mixed with the DNA of a control person labeled with a different fluorescent dye. Mixed together there are hybridized to one microarray. On one microarray each region of the genome is represented by several probes. More probes per genome, greater resolution of the microarray and smaller changes can be visible.
Where the subject carries a deletion compared to the control (missing a piece of the DNA) then the array lights up green and when additional piece is present: red (duplication).
According to data from the Institute of Human Genetics, University of Nijmegen / Netherlands (Conference Paper Koolen DA et al., Meeting of the European Society of Human Genetics, Nice 2007) in about 30% of patients with malformation/ retardation syndromes, which clinically could not be clearly assigned, the causal changes were found using array CGH technique. In about 1/3 of the cases the changes were less than 1 million base pairs. Frequently, overlooked by chromosome analysis changes include a duplication on chromosome Xq28 including the MECP2 gene (size about 2 million base pairs) or a deletion on chromosome 17q21, including the MAPT gene (size 0.6 million base pairs).
We use the Agilent Oligo CGH array system with 180000 oligos (180k array) with a maximum resolution of about 17 kb, or about 200 times higher than the chromosome analysis. In case we find unclassified and not clearly disease-causing changes, we perform their validation by quantitative real time PCR.
In our publications, you can read about the examples (Borozdin et al. 2007) and (Unger et al. 2008).
For the investigation, we need an EDTA blood sample (3-5 ml). If you have any further questions, please contact us.
Here you will find a press report on array CGH:Bio Pro.
Here you can find more information and a list of the investigated loci: