1. ¹Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
2. ²Oxford Genetics Knowledge Park, Wellcome Trust Centre for Human Genetics, Oxford, UK
3. ³Oxford NIHR Biomedical Research Centre, Oxford Radcliffe Hospitals NHS Trust, Churchill Hospital, Oxford, UK
4. ⁴Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
5. ⁵Unit of Pediatrics and Medical Genetics, Department for Mental Retardation, IRCCS Oasi Research Institute, Troina, Italy
6. ⁶Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland
7. ⁷Department of Molecular Medicine and Surgery, Karolinska University Hospital, Stockholm, Sweden

Correspondence: Dr BBA de Vries, Department of Human Genetics 849, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen 6500 HB, The Netherlands. Tel: +31 24 36 139 46; Fax: +31 24 36 687 74; E-mail: b.devries@antrg.umcn.nl

Received 11 May 2007; Revised 30 October 2007; Accepted 14 November 2007; Published online 9 January 2008.

Abstract

Genome-wide analysis of DNA copy-number changes using microarray-based technologies has enabled the detection of de novo cryptic chromosome imbalances in approximately 10% of individuals with mental retardation. So far, the majority of these submicroscopic microdeletions/duplications appear to be unique, hampering clinical interpretation and genetic counselling. We hypothesised that the genomic regions involved in these de novo submicroscopic aberrations would be candidates for recurrent copy-number changes in individuals with mental retardation. To test this hypothesis, we used multiplex ligation-dependent probe amplification (MLPA) to screen for copy number changes at eight genomic candidate regions in a European cohort of 710 individuals with idiopathic mental retardation. By doing so, we failed to detect additional submicroscopic rearrangements, indicating that the anomalies tested are non-recurrent in this cohort of patients. The break points flanking the candidate regions did not contain low copy repeats and/or sequence similarities, thus providing an explanation for its non-recurrent nature. On the basis of these data, we propose that the use of genome-wide microarrays is indicated when testing for copy-number changes in individuals with idiopathic mental retardation.