title: Detection of pathogenic copy number variants in children with idiopathic intellectual disability using 500 K SNP array genomic hybridization.
abstract: BACKGROUND
  Array genomic hybridization is being used clinically to detect pathogenic copy number variants in children with intellectual disability and other birth defects. However, there is no agreement regarding the kind of array, the distribution of probes across the genome, or the resolution that is most appropriate for clinical use.
  
  
  RESULTS
  We performed 500 K Affymetrix GeneChip array genomic hybridization in 100 idiopathic intellectual disability trios, each comprised of a child with intellectual disability of unknown cause and both unaffected parents. We found pathogenic genomic imbalance in 16 of these 100 individuals with idiopathic intellectual disability. In comparison, we had found pathogenic genomic imbalance in 11 of 100 children with idiopathic intellectual disability in a previous cohort who had been studied by 100 K GeneChip array genomic hybridization. Among 54 intellectual disability trios selected from the previous cohort who were re-tested with 500 K GeneChip array genomic hybridization, we identified all 10 previously-detected pathogenic genomic alterations and at least one additional pathogenic copy number variant that had not been detected with 100 K GeneChip array genomic hybridization. Many benign copy number variants, including one that was de novo, were also detected with 500 K array genomic hybridization, but it was possible to distinguish the benign and pathogenic copy number variants with confidence in all but 3 (1.9%) of the 154 intellectual disability trios studied.
  
  
  CONCLUSIONS
  Affymetrix GeneChip 500 K array genomic hybridization detected pathogenic genomic imbalance in 10 of 10 patients with idiopathic developmental disability in whom 100 K GeneChip array genomic hybridization had found genomic imbalance, 1 of 44 patients in whom 100 K GeneChip array genomic hybridization had found no abnormality, and 16 of 100 patients who had not previously been tested. Effective clinical interpretation of these studies requires considerable skill and experience.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada. frid@interchange.ubc.ca
authors.forename: Jm
authors.initials: J
authors.lastname: Friedman
authors.forename: Shelin
authors.initials: S
authors.lastname: Adam
authors.forename: Laura
authors.initials: L
authors.lastname: Arbour
authors.forename: Linlea
authors.initials: L
authors.lastname: Armstrong
authors.forename: Agnes
authors.initials: A
authors.lastname: Baross
authors.forename: Patricia
authors.initials: P
authors.lastname: Birch
authors.forename: Cornelius
authors.initials: C
authors.lastname: Boerkoel
authors.forename: Susanna
authors.initials: S
authors.lastname: Chan
authors.forename: David
authors.initials: D
authors.lastname: Chai
authors.forename: Allen D
authors.initials: AD
authors.lastname: Delaney
authors.forename: Stephane
authors.initials: S
authors.lastname: Flibotte
authors.forename: William T
authors.initials: WT
authors.lastname: Gibson
authors.forename: Sylvie
authors.initials: S
authors.lastname: Langlois
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Lemyre
authors.forename: H Irene
authors.initials: HI
authors.lastname: Li
authors.forename: Patrick
authors.initials: P
authors.lastname: MacLeod
authors.forename: Joan
authors.initials: J
authors.lastname: Mathers
authors.forename: Jacques L
authors.initials: JL
authors.lastname: Michaud
authors.forename: Barbara C
authors.initials: BC
authors.lastname: McGillivray
authors.forename: Millan S
authors.initials: MS
authors.lastname: Patel
authors.forename: Hong
authors.initials: H
authors.lastname: Qian
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: Margot I
authors.initials: MI
authors.lastname: Van Allen
authors.forename: Siu-Li
authors.initials: SL
authors.lastname: Yong
authors.forename: Farah R
authors.initials: FR
authors.lastname: Zahir
authors.forename: Patrice
authors.initials: P
authors.lastname: Eydoux
authors.forename: Marco A
authors.initials: MA
authors.lastname: Marra
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult