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.
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.
Authors: Bixia Xiang; Hongbo Zhu; Yiping Shen; David T Miller; Kangmo Lu; Xiaofeng Hu; Hans C Andersson; Tarachandra M Narumanchi; Yueying Wang; Jose E Martinez; Bai-Lin Wu; Peining Li; Marilyn M Li; Tian-Jian Chen; Yao-Shan Fan Journal: J Mol Diagn Date: 2010-01-21 Impact factor: 5.568
Authors: David T Miller; Margaret P Adam; Swaroop Aradhya; Leslie G Biesecker; Arthur R Brothman; Nigel P Carter; Deanna M Church; John A Crolla; Evan E Eichler; Charles J Epstein; W Andrew Faucett; Lars Feuk; Jan M Friedman; Ada Hamosh; Laird Jackson; Erin B Kaminsky; Klaas Kok; Ian D Krantz; Robert M Kuhn; Charles Lee; James M Ostell; Carla Rosenberg; Stephen W Scherer; Nancy B Spinner; Dimitri J Stavropoulos; James H Tepperberg; Erik C Thorland; Joris R Vermeesch; Darrel J Waggoner; Michael S Watson; Christa Lese Martin; David H Ledbetter Journal: Am J Hum Genet Date: 2010-05-14 Impact factor: 11.025