Identification of non-recurrent submicroscopic genome imbalances: The advantage of genome-wide microarrays over targeted approaches

David A. Koolen, Erik A. Sistermans, Willy Nilessen, Samantha J.L. Knight, Regina Regan, Yan T. Liu, R. Frank Kooy, Liesbeth Rooms, Corrado Romano, Marco Fichera, Albert Schinzel, Alessandra Baumer, Britt Marie Anderlid, Jacqueline Schoumans, Ad Geurts van Kessel, Magnus Nordenskjold, Bert B.A. de Vries*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)395-400
Number of pages6
JournalEuropean Journal of Human Genetics
Issue number3
Publication statusPublished - 1 Mar 2008

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