Diagnostic Genome Profiling in Mental Retardation

  • David A. Koolen
  • Joris A. Veltman
  • Bert B. A. de VriesEmail author
Part of the Advances in Neurobiology book series (NEUROBIOL, volume 2)


Mental retardation occurs in 2–3% of the general population. Chromosomal aberrations are one of the major causes of mental retardation, but despite the significant progresses in the elucidation of mental retardation, the genetic causes of mental retardation remain largely unknown. Conventional karyotyping using light microscopy has been the primary tool for diagnosing chromosomal aberrations in mental retardation for more than 30 years. Several novel methods based on fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR)-based methods have been developed over recent years to increase the detection yield of copy-number changes (CNVs) at the submicroscopic level (<5–10 Mb) in individuals with mental retardation. In the last few years, genome-wide microarray technologies have resulted in significant increases in the resolution of chromosome analysis. Microarray ­technologies allow genome-wide detection of multiple genomic submicroscopic CNVs. The implementation of these novel molecular-cytogenetic technologies not only showed that submicroscopic genomic aberrations are an important cause of mental retardation, resulting in newly recognized microdeletion/microduplication syndromes, but also allowed for the identification of novel genes causing mental retardation.


Copy-number variants Genome profiling Mental retardation Microarray Molecular karyotyping Syndrome 



This work was supported by grants from the Netherlands Organization for Health Research and Development (ZON-MW) (D.A.K., J.A.V., and B.B.A.d.V.), and the Hersenstichting Nederland (B.B.A.d.V.).


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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • David A. Koolen
  • Joris A. Veltman
  • Bert B. A. de Vries
    • 1
    Email author
  1. 1.Department of Human Genetics, Nijmegen Centre for Molecular Life SciencesRadboud University Nijmegen Medical CentreNijmegenThe Netherlands

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