Array-based comparative genomic hybridization analysis of 1176 consecutive clinical genetics investigations.
OBJECTIVE
Cytogenetic investigations are useful for etiologic determinations of mental retardation, developmental delay, multiple congenital anomalies, and pregnancy complications; however, the causes remain elusive in a majority of cases despite high-resolution cytogenetic studies and multiple fluorescence in situ hybridization examinations. Array-based comparative genomic hybridization has the ability to examine the genome at a higher resolution and may yield an increased detection of genetic abnormalities. The purpose of this study was to assess the use of array-based comparative genomic hybridization in a clinical genetics setting.


METHODS
DNA from 1176 patients was analyzed using a bacterial artificial chromosome array-based comparative genomic hybridization platform. All abnormal cases were confirmed by fluorescence in situ hybridization and parental studies were completed when possible.


RESULTS
Of the 1176 patients included in this survey, 163 showed a genomic imbalance identified by array-based comparative genomic hybridization. Of these 163 cases, 116 had a clinically relevant genetic abnormality. A total of 9.8% (116 of 1176 cases) were determined to exhibit a causative genomic imbalance. Twenty-five of the 116 abnormal cases had a previously identified cytogenetic abnormality yielding an increased detection rate of 7.9% (91 of 1146) in cases with normal or no cytogenetics.


CONCLUSIONS
Array-based comparative genomic hybridization increases the overall abnormality detection rate, thus improving the diagnostic potential of clinical cytogenetics investigations.
Pickering
Diane L
DL
Department of Pediatrics and Human Genetics Laboratory, Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Eudy
James D
JD
Olney
Ann Haskins
AH
Dave
Bhavana J
BJ
Golden
Denae
D
Stevens
Jadd
J
Sanger
Warren G
WG
D000015:Abnormalities, Multiple / Q000235:genetics*; D000465:Algorithms; D002869:Chromosome Aberrations; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D003582:Cytogenetics / Q000379:methods*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D046228:Microarray Analysis / Q000379:methods*; D009693:Nucleic Acid Hybridization / Q000379:methods*