Koolen David A, Sistermans Erik A, Nilessen Willy, Knight Samantha J L, Regan Regina, Liu Yan T, Kooy R Frank, Rooms Liesbeth, Romano Corrado, Fichera Marco, Schinzel Albert, Baumer Alessandra, Anderlid Britt-Marie, Schoumans Jacqueline, van Kessel Ad Geurts, Nordenskjold Magnus, de Vries Bert B A
Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Eur J Hum Genet. 2008 Mar;16(3):395-400. doi: 10.1038/sj.ejhg.5201975. Epub 2008 Jan 9.
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.
