Application of array comparative genomic hybridization in 256 patients with developmental delay or intellectual disability

Abstract

We used whole-genome exon-targeted oligonucleotide array comparative genomic hybridization (array CGH) in a cohort of 256 patients with developmental delay (DD)/intellectual disability (ID) with or without dysmorphic features, additional neurodevelopmental abnormalities, and/or congenital malformations. In 69 patients, we identified 84 non-polymorphic copy-number variants, among which 41 are known to be clinically relevant, including two recently described deletions, 4q21.21q21.22 and 17q24.2. Chromosomal microarray analysis revealed also 15 potentially pathogenic changes, including three rare deletions, 5q35.3, 10q21.3, and 13q12.11. Additionally, we found 28 copy-number variants of unknown clinical significance. Our results further support the notion that copy-number variants significantly contribute to the genetic etiology of DD/ID and emphasize the efficacy of the detection of novel candidate genes for neurodevelopmental disorders by whole-genome array CGH.

Fig. 1

Results of array CGH analyses: a patient 51, showing a de novo ∼250-kb deletion in 13q12.11; b patient 45, demonstrating a de novo ∼720-kb deletion at 5q35.3; and c patient 50, showing a rare ∼1.4-Mb deletion in 10q21.3. The red dots denote the deleted region. Gene content in the deleted region on: d chromosome 13q12.11; e chromosome 5q35.3 (compared with the critical region of the Sotos syndrome and 5q35.3 subtelomeric deletion syndrome); and f chromosome 10q21.3 (UCSC genome browser, http://genome.ucsc.edu/)