Conflict of interest: none.
Customized high resolution CGH-array for clinical diagnosis reveals additional genomic imbalances in previous well-defined pathological samples
Article first published online: 24 JUN 2013
Copyright © 2013 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 8, pages 1950–1960, August 2013
How to Cite
2013. Customized high-resolution CGH-array for clinical diagnosis reveals additional genomic imbalances in previous well-defined pathological samples. Am J Med Genet Part A. 161A:1950–1960., , , , , , , , , , , , , , , , .
- Issue published online: 24 JUL 2013
- Article first published online: 24 JUN 2013
- Manuscript Accepted: 3 MAR 2013
- Manuscript Received: 27 JUN 2011
- FIBHULP (Redes/FIBHULP08.Nevado)
- chromosomal imbalances;
- customized array;
High-resolution array comparative genomic hybridization (aCGH) is a powerful molecular cytogenetic tool that is being adopted for diagnostic evaluation of genomic imbalances and study disease mechanisms and pathogenesis. We report on the design and use, of a custom whole-genome oligonucleotide-based array (called KaryoArray®v3.0; Agilent-based 8 × 60 K) for diagnostic setting, which was able to detect new and unexpected rearrangements in 11/63 (∼17.5%) of previous known pathological cases associated with known genetic disorders, and in the second step it identified at least one causal genomic imbalance responsible of the phenotype in ∼20% of patients with psychomotor development delay and/or intellectual disability. To validate the array, first; we blindly tested 120 samples; 63 genomic imbalances that had previously been detected by karyotyping, FISH and/or MLPA, and 57 sex-matched control samples from healthy individuals; secondly a prospective study of 540 patients with intellectual disabilities, autism spectrum disorder and multiple congenital anomalies were evaluated to confirm the utility of the tool. These data indicate that implementation of array technologies as the first-tier test may reveal that additional genomic imbalances could co-exist in patients with trisomies and classical del/dup syndromes, suggesting that aCGH may also be indicated in these individuals, at least when phenotype does not match completely with genotype. © 2013 Wiley Periodicals, Inc.