|Cheung, Sau Wai|
|Chinault, A Craig|
|Van Den Veyver, Ignatia|
Submitted to: American Journal of Obstetrics and Gynecology
Publication Type: Abstract Only
Publication Acceptance Date: 12/1/2007
Publication Date: 12/1/2007
Citation: Cheung, S.W., Shaw, C., Kang, S., Simovich, M., Pursley, A., Darilek, S., Ward, P., Chinault, A.C., Patel, A., Lupski, J., Beaudet, A., Eng, C., Van Den Veyver, I. 2007. Rapid prenatal diagnosis of cytogenetic abnormalities by array CGH analysis [abstract]. American Journal of Obstetrics and Gynecology. 197(6)Supplement:S173.
Technical Abstract: Array CGH analysis has been shown to be highly accurate for rapid detection of chromosomal aneuploidies and submicroscopic deletions or duplications on fetal DNA samples in a clinical prenatal diagnostic setting. The objective of this study is to present our "post-validation phase" experience with this test. All women underwent chorionic villus sampling (CVS) or amniocentesis for standard indications, received genetic counseling, and provided informed consent. DNA was prepared directly or after whole genome amplification from CVS and amniotic fluid (AF) and tested for maternal cell contamination. Back-up cell cultures were established and standard karyotypes performed either in our lab or elsewhere for all samples. A blood sample from both parents was requested to determine the origin of copy number variants (CNVs) detected in the fetus, if needed. A total of 228 clinical cases were referred for clinical array CGH testing: 39 CVS (17%) and 189 AF (83%). The most common indications were advanced maternal age (n=73, 35%), abnormal ultrasound findings (n=52, 23%), family history of genomic disorders or specific cytogenic abnormalities (n=19, 8%), family history of other genetic disorders (n=27, 12%), and further clarification of specific cytogenetic abnormalities on karyotype (n=11, 5%). Other indications included abnormal serum screening results, parental concern, and previous pregnancy loss. Copy number changes were detected in 29 samples, for a detection rate of 12.7%. There were 21 familial CNVs (9%), inherited from a phenotypically normal parent. The combined detection rate for genomic disorders and cytogenetic abnormalities was 3.5% (8/228). Our data confirm that array CGH yields highly accurate results on CVS and AF in less than 2 weeks in most cases. Results can be obtained in as early as 4 days from direct CVS or amniotic fluid.