High prevalence of array comparative genomic hybridization abnormalities in adults with unexplained intellectual disability

Abstract

Purpose: 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 highresolution 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. Conclusion: 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. Genet Med 2010:12(1):32-38.

Comprehensive Evaluation of the Child With Intellectual Disability or Global Developmental Delays

“…Nevertheless, the diagnostic yield for all current CMA is estimated at 12% for patients with GDD/ID. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] CMA is the single most efficient diagnostic test, after the history and examination by a specialist in GDD/ID.…”

Diagnostic yield of array comparative genomic hybridization in adults with autism spectrum disorders

“…7 There are no studies of the diagnostic yield of aCGH in adults with ASD, although one study of 45 adult patients with intellectual disability reported a diagnostic yield of 22% and suggested the yield of aCGH may be higher in an adult as compared with a pediatric population. 8 It could be hypothesized that the diagnostic yield of genetic testing in an adult ASD population would be lower than in a pediatric population because of childhood mortality from epilepsy or congenital anomalies. Alternatively, the yield could be higher in adults if chromosomal anomalies were not previously identified because of the limitations of prior testing or the lack of prior genetic evaluation.…”

High Incidence of Copy Number Variants in Adults with Intellectual Disability and Co-morbid Psychiatric Disorders

“…At present, there is little knowledge of the genetics of ID and co-morbid psychiatric disorder in adults. Nevertheless, CMA and whole exome sequencing could shed light on the genetic diagnoses in adults with idiopathic ID (Baker et al 2012 ; Posey et al 2016 ; Taylor et al 2010 ; Wolfe et al 2016 ). Here, we report the genetic analysis of 100 adult patients affected by ID and psychiatric and/or behavioural disorders.…”