Molecular karyotyping of patients with unexplained mental retardation by SNP arrays: a multicenter study

Hum Mutat. 2009 Jul;30(7):1082-92. doi: 10.1002/humu.21015.


Genomic microarrays have been implemented in the diagnosis of patients with unexplained mental retardation. This method, although revolutionizing cytogenetics, is still limited to the detection of rare de novo copy number variants (CNVs). Genome-wide single nucleotide polymorphism (SNP) microarrays provide high-resolution genotype as well as CNV information in a single experiment. We hypothesize that the widespread use of these microarray platforms can be exploited to greatly improve our understanding of the genetic causes of mental retardation and many other common disorders, while already providing a robust platform for routine diagnostics. Here we report a detailed validation of Affymetrix 500k SNP microarrays for the detection of CNVs associated to mental retardation. After this validation we applied the same platform in a multicenter study to test a total of 120 patients with unexplained mental retardation and their parents. Rare de novo CNVs were identified in 15% of cases, showing the importance of this approach in daily clinical practice. In addition, much more genomic variation was observed in these patients as well as their parents. We provide all of these data for the scientific community to jointly enhance our understanding of these genomic variants and their potential role in this common disorder.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Dosage
  • Genetic Variation
  • Heterozygote
  • Humans
  • Intellectual Disability / genetics*
  • Karyotyping*
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide*
  • Reagent Kits, Diagnostic / standards
  • Uniparental Disomy


  • Reagent Kits, Diagnostic