title: Microarray-based CGH detects chromosomal mosaicism not revealed by conventional cytogenetics.
abstract: Somatic chromosomal mosaicism is a well-established cause for birth defects, mental retardation, and, in some instances, specific genetic syndromes. We have developed a clinically validated, targeted BAC clone array as a platform for comparative genomic hybridization (aCGH) to enable detection of a wide range of pathologic copy number changes in DNA. It is designed to provide high sensitivity to detect well-characterized submicroscopic micro-deletion and duplication disorders while at the same time minimizing detection of variation of uncertain clinical significance. In the course of studying 2,585 samples submitted to our clinical laboratory, chromosomal mosaicism was detected in 12 patient samples; 10 of these cases were reported to have had a normal blood chromosome analysis. This enhanced ability of aCGH to detect mosaicism missed by routine chromosome analysis may be due to some combination of testing multiple cell lineages and/or failure of cytogenetically abnormal T lymphocytes to respond to mitogens. This suggests that aCGH may detect somatic chromosomal mosaicism that would be missed by conventional cytogenetics.
authors.affiliation: Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030. scheung@bcm.tmc.edu
authors.forename: Sau W
authors.initials: SW
authors.lastname: Cheung
authors.forename: Chad A
authors.initials: CA
authors.lastname: Shaw
authors.forename: Daryl A
authors.initials: DA
authors.lastname: Scott
authors.forename: Ankita
authors.initials: A
authors.lastname: Patel
authors.forename: Trilochan
authors.initials: T
authors.lastname: Sahoo
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Bacino
authors.forename: Amber
authors.initials: A
authors.lastname: Pursley
authors.forename: Jiangzhen
authors.initials: J
authors.lastname: Li
authors.forename: Robert
authors.initials: R
authors.lastname: Erickson
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Gropman
authors.forename: David T
authors.initials: DT
authors.lastname: Miller
authors.forename: Margretta R
authors.initials: MR
authors.lastname: Seashore
authors.forename: Anne M
authors.initials: AM
authors.lastname: Summers
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: A Craig
authors.initials: AC
authors.lastname: Chinault
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Beaudet
authors.forename: V Reid
authors.initials: VR
authors.lastname: Sutton
mesh_terms: D002869:Chromosome Aberrations / Q000145:classification; D002874:Chromosome Mapping; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D009030:Mosaicism; D009693:Nucleic Acid Hybridization / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012680:Sensitivity and Specificity; D014314:Trisomy