Abnormalities in DNA copy number are frequently found in patients with multiple 
anomaly syndromes and mental retardation. Array-based comparative genomic 
hybridization (array-CGH) is a high-resolution, whole-genome technology that 
improves detection of submicroscopic aberrations underlying these syndromes. 
Eight patients with mental disability, multiple congenital anomalies, and 
dysmorphic features were screened for submicroscopic chromosomal imbalances 
using the GenoSensor Array 300 Chip. Subtelomeric aberrations previously 
detected by fluorescence in situ hybridization (FISH) analysis were confirmed in 
two patients, and accurate diagnosis was provided in two previously undiagnosed 
complex cases. Microdeletions at 15q11.2-q13 in a newborn with hypotonia, 
cryptorchidism, and hypopigmentation were detected with few discrepancies 
between the array results and FISH analysis. Contiguous microdeletion of GSCL, 
HIRA and TBX1 genes at 22q11.2 was identified in a previously undiagnosed boy 
with an unusual presentation of the VCF/DiGeorge spectrum. In a newborn with 
aniridia, a borderline false-negative WT1 deletion was observed, most probably 
because of differences between the size of the genomic deletion and the 
microarray probe. A false-positive rate of 0.2% was calculated for 
clone-by-clone analysis, whereas the per patient false-positive rate was 20%. 
Array-CGH is a powerful tool for the rapid and accurate detection of genetic 
disorders associated with copy number abnormalities and can significantly 
improve clinical genetic diagnosis and care.