title: High prevalence of array comparative genomic hybridization abnormalities in adults with unexplained intellectual disability.
abstract: OBJECTIVE
  Array comparative genomic hybridization is now a widely used clinical tool for the evaluation of intellectual disability. The current 10% yield of positive findings is based largely on pediatric data. Adults with unexplained intellectual disability have not been systematically studied with array comparative genomic hybridization. Here, we report our initial experience with array comparative genomic hybridization testing on 45 adults with unexplained intellectual disability referred to an adult genetics clinic.
  
  
  METHODS
  Beginning in 2006, we applied clinically available array comparative genomic hybridization testing to adults referred with an intellectual disability phenotype. The initial platform used was an early generation targeted or constitutional array, which was replaced by our current platform using more than 5000 bacterial artificial chromosome clones with an average resolution of 500 Kb and targeting 114 disease loci. All patients also underwent high-resolution karyotype analysis and molecular testing for Fragile X syndrome.
  
  
  RESULTS
  Our population comprised 45 patients with unexplained intellectual disability (18 men and 27 women) with an average age of 35.1 years. Most patients had not been evaluated by genetics clinics since childhood or had never undergone a genetic evaluation; only two had documentation of prior normal karyotype studies. Three subjects had abnormal high-resolution chromosome studies, which were also confirmed by array comparative genomic hybridization. Seven of the remaining 42 patients (17%) had novel genomic losses identified only by array comparative genomic hybridization.
  
  
  CONCLUSIONS
  Abnormal genomic losses detected by array comparative genomic hybridization are prevalent in adults with unexplained intellectual disability. Our data showing abnormalities in 22% and 17% of overall patients and of cases with normal karyotypes, respectively, suggest that the yield of array comparative genomic hybridization in adults with unexplained intellectual disability may be higher than in pediatric populations.
authors.affiliation: Department of Medicine, Adult Medical Genetics Program, University of Colorado Denver, Denver, Colorado, USA. matthew.taylor@ucdenver.edu
authors.forename: Matthew R G
authors.initials: MR
authors.lastname: Taylor
authors.forename: Jean
authors.initials: J
authors.lastname: Jirikowic
authors.forename: Cara
authors.initials: C
authors.lastname: Wells
authors.forename: Michelle
authors.initials: M
authors.lastname: Springer
authors.forename: Loris
authors.initials: L
authors.lastname: McGavran
authors.forename: Brenda
authors.initials: B
authors.lastname: Lunt
authors.forename: Karen
authors.initials: K
authors.lastname: Swisshelm
mesh_terms: D000328:Adult; D055028:Comparative Genomic Hybridization / Q000706:statistics & numerical data*; D005006:Ethnicity; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000209:etiology / Q000235:genetics*; D007360:Intelligence / Q000235:genetics; D007621:Karyotyping; D008297:Male; D015995:Prevalence; D044469:Racial Groups