Array-based comparative genomic hybridization analysis of 1176 consecutive clinical genetics investigations.
Pickering, Diane L. MS, CLSp (CG) 1; Eudy, James D. PhD 2; Olney, Ann Haskins MD, FACMG 3; Dave, Bhavana J. PhD, FACMG 1; Golden, Denae BS, CLSp (CG) 1; Stevens, Jadd BS, CLSp (CG, MB) 1; Sanger, Warren G. PhD, FACMG 1
Genetics in Medicine.
10(4):262-266, April 2008.
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Purpose: 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.
Conclusion: Array-based comparative genomic hybridization increases the overall abnormality detection rate, thus improving the diagnostic potential of clinical cytogenetics investigations.
(C)2008The American College of Medical Genetics