Analysis of Chromosomal Aberrations in Patients with Mental Retardation Using the Array-CGH Technique: a Single Czech Centre Experience

Zrnová, E.; Vranová, V.; Slámová, I.; Gaillyová, R.; Kuglík, Petr

doi:10.14712/fb2011057050206

Folia Biologica > Archive > 2011, Vol. 57 > Issue 5 > Analysis of Chromosomal Aberrations in…

Fol. Biol. 2011, 57, 206-215

https://doi.org/10.14712/fb2011057050206

Analysis of Chromosomal Aberrations in Patients with Mental Retardation Using the Array-CGH Technique: a Single Czech Centre Experience

E. Zrnová^1,2, V. Vranová^1,2, I. Slámová^1,2, R. Gaillyová², Petr Kuglík^1,2

¹Masaryk University, Faculty of Science, Institute of Experimental Biology, Department of Genetics and Molecular Biology, Brno, Czech Republic
²University Hospital Brno, Department of Medical Genetics, Integrated Laboratory of Molecular Cytogenetics, Brno, Czech Republic

Received April 2011
Accepted May 2011

Submicroscopic structural chromosomal aberrations (microduplications and microdeletions) are believed to be common causes of mental retardation. These so-called copy number variations can now be routinely detected using various platforms for array-based comparative genomic hybridization (array-CGH), which allow genome-wide identification of pathogenic genomic imbalances. In this study, oligonucleotide-based array-CGH was used to investigate a panel of 23 patients with mental retardation and developmental delay, dysmorphic features or congenital anomalies. Array-CGH confirmed or revealed 16 chromosomal aberrations in a total of 12 patients. Analysis of parental samples showed that five aberrations had occurred de novo: del(1)(p36.33p36.23), del(4)(p16.3p16.2) joined with dup(8)(p23.3p23.1), del(6)(q14.1q15), del(11)(q13.1q13.4). Three aberrations appeared to be inherited from an unaffected parent: dup(3)(q29), del(6)(q12), dup(16)(p13.11). Six aberrations appeared to be inherited from a parental carrier: del(1)(p36.33) joined with dup(12)(q24.32), del(21)(q22.2q22.3) joined with dup(11)(q24.2q25), del(X)(q22.3) and del(1)(q21.1). In two cases, parents were not available for testing: del(17)(q11.2q12) and del(2)(q24.3q31.1). Our results show that the use of oligonucleotide-based array-CGH in a clinical diagnostic laboratory increases the detection rate of pathogenic submicroscopic chromosomal aberrations in patients with mental retardation and congenital abnormalities, but it also presents challenges for clinical interpretation of the results (i.e. distinguishing between pathogenic and benign variants). Difficulties with analysis notwithstanding, the array-CGH is shown to be a sensitive, fast and reliable method for genome-wide screening of chromosomal aberrations in patients with mental retardation and congenital abnormalities.

Keywords

array-CGH, DNA microarray, mental retardation, chromosomal aberrations.

Funding

This study was supported by MSM0021622415 from the Ministry of Education, Youth and Sports, Czech Republic; by Research Council of Norway, The Yggdrasil mobility programme (202752); by European Science Foundation (ESF) ‘Frontiers of Functional Genomics’ (3419).