Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features

• Published in: Journal of medical genetics Vol. 41; no. 4; pp. 241 - 248
• Main Authors: Shaw-Smith, C, Redon, R, Rickman, L, Rio, M, Willatt, L, Fiegler, H, Firth, H, Sanlaville, D, Winter, R, Colleaux, L, Bobrow, M, Carter, N P
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01-04-2004; BMJ; BMJ Publishing Group LTD; BMJ Publishing Group; BMJ Group
• Subjects: Adolescent; Adult; array-CGH; Arrays; Biological and medical sciences; Child; Child, Preschool; Chromosome Aberrations; Chromosome Deletion; Chromosome Disorders; Chromosome Disorders - genetics; Chromosomes; Cloning; Cytogenetic Analysis; Cytogenetic Analysis - methods; Female; Genetics; Genomes; Human genetics; Humans; Intellectual Disability; Intellectual Disability - genetics; Learning disabilities; Learning Disorders; Learning Disorders - genetics; Life Sciences; Male; Medical genetics; Medical sciences; mental retardation; microdeletion; microduplication; Oligonucleotide Array Sequence Analysis; Oligonucleotide Array Sequence Analysis - methods; Original; Patients; United Kingdom > UK; United States > US; Germany; Chromosomal aberration; Human; Learning disability; Intellectual deficiency; Deletion; Abnormal chromosome; Developmental disorder; Chromosome duplication; Mental retardation
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.2003.017731

The underlying causes of learning disability and dysmorphic features in many patients remain unidentified despite extensive investigation. Routine karyotype analysis is not sensitive enough to detect subtle chromosome rearrangements (less than 5 Mb). The presence of subtle DNA copy number changes was investigated by array-CGH in 50 patients with learning disability and dysmorphism, employing a DNA microarray constructed from large insert clones spaced at approximately 1 Mb intervals across the genome. Twelve copy number abnormalities were identified in 12 patients (24% of the total): seven deletions (six apparently de novo and one inherited from a phenotypically normal parent) and five duplications (one de novo and four inherited from phenotypically normal parents). Altered segments ranged in size from those involving a single clone to regions as large as 14 Mb. No recurrent deletion or duplication was identified within this cohort of patients. On the basis of these results, we anticipate that array-CGH will become a routine method of genome-wide screening for imbalanced rearrangements in children with learning disability.