Oligonucleotide Microarray Analysis of Genomic Imbalance in Children with Mental Retardation

• Published in: American journal of human genetics Vol. 79; no. 3; pp. 500 - 513
• Main Authors: Friedman, J.M., Baross, Ágnes, Delaney, Allen D., Ally, Adrian, Arbour, Laura, Asano, Jennifer, Bailey, Dione K., Barber, Sarah, Birch, Patricia, Brown-John, Mabel, Cao, Manqiu, Chan, Susanna, Charest, David L., Farnoud, Noushin, Fernandes, Nicole, Flibotte, Stephane, Go, Anne, Gibson, William T., Holt, Robert A., Jones, Steven J.M., Kennedy, Giulia C., Krzywinski, Martin, Langlois, Sylvie, Li, Haiyan I., McGillivray, Barbara C., Nayar, Tarun, Pugh, Trevor J., Rajcan-Separovic, Evica, Schein, Jacqueline E., Schnerch, Angelique, Siddiqui, Asim, Van Allen, Margot I., Wilson, Gary, Yong, Siu-Li, Zahir, Farah, Eydoux, Patrice, Marra, Marco A.
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.09.2006; University of Chicago Press; Cell Press; The American Society of Human Genetics
• Subjects: Adult and adolescent clinical studies; Biological and medical sciences; Child; Children & youth; Chromosome Aberrations; Chromosomes; Gene Dosage; General aspects. Genetic counseling; Genome, Human; Genomics; Humans; Intellectual deficiency; Intellectual disabilities; Intellectual Disability - diagnosis; Medical genetics; Medical sciences; Oligonucleotide Array Sequence Analysis; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Sequence Deletion; Human; Genomics; Intellectual deficiency; Genetics; Developmental disorder; Oligonucleotide; Mental retardation; Child
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/507471

The cause of mental retardation in one-third to one-half of all affected individuals is unknown. Microscopically detectable chromosomal abnormalities are the most frequently recognized cause, but gain or loss of chromosomal segments that are too small to be seen by conventional cytogenetic analysis has been found to be another important cause. Array-based methods offer a practical means of performing a high-resolution survey of the entire genome for submicroscopic copy-number variants. We studied 100 children with idiopathic mental retardation and normal results of standard chromosomal analysis, by use of whole-genome sampling analysis with Affymetrix GeneChip Human Mapping 100K arrays. We found de novo deletions as small as 178 kb in eight cases, de novo duplications as small as 1.1 Mb in two cases, and unsuspected mosaic trisomy 9 in another case. This technology can detect at least twice as many potentially pathogenic de novo copy-number variants as conventional cytogenetic analysis can in people with mental retardation.