Funding sources: This work was funded by Signature Genomic Laboratories, PerkinElmer, Inc.
Experience with microarray-based comparative genomic hybridization for prenatal diagnosis in over 5000 pregnancies
Article first published online: 2 AUG 2012
© 2012 John Wiley & Sons, Ltd.
Volume 32, Issue 10, pages 976–985, October 2012
How to Cite
Shaffer, L. G., Dabell, M. P., Fisher, A. J., Coppinger, J., Bandholz, A. M., Ellison, J. W., Ravnan, J. B., Torchia, B. S., Ballif, B. C. and Rosenfeld, J. A. (2012), Experience with microarray-based comparative genomic hybridization for prenatal diagnosis in over 5000 pregnancies. Prenat. Diagn., 32: 976–985. doi: 10.1002/pd.3945
Conflicts of interest: L.G.S., M.P.D., J.C., A.M.B., J.W.E., J.B.R., B.S.T., B.C.B., and J.A.R. are current or former employees of Signature Genomic Laboratories, PerkinElmer, Inc. J.C., J.B.R., L.G.S., and B.C.B. own stock in PerkinElmer, Inc. A.J.F. has no conflicts to disclose.
- Issue published online: 1 OCT 2012
- Article first published online: 2 AUG 2012
- Manuscript Accepted: 1 JUL 2012
- Manuscript Revised: 11 JUN 2012
- Manuscript Received: 11 APR 2012
To demonstrate the usefulness of microarray testing in prenatal diagnosis based on our laboratory experience.
Prenatal samples received from 2004 to 2011 for a variety of indications (n = 5003) were tested using comparative genomic hybridization-based microarrays targeted to known chromosomal syndromes with later versions of the microarrays providing backbone coverage of the entire genome.
The overall detection rate of clinically significant copy number alterations (CNAs) among unbiased, nondemise cases was 5.3%. Detection rates were 6.5% and 8.2% for cases referred with abnormal ultrasounds and fetal demise, respectively. The overall rate of findings with unclear clinical significance was 4.2% but would reduce to 0.39% if only de novo CNAs were considered. In cases with known chromosomal rearrangements in the fetus or parent, 41.1% showed CNAs related to the rearrangements, whereas 1.3% showed clinically significant CNAs unrelated to the karyotype. Finally, 71% of the clinically significant CNAs found by microarray were below the resolution of conventional karyotyping of fetal chromosomes.
Microarray analysis has advantages over conventional cytogenetics, including the ability to more precisely characterize CNAs associated with abnormal karyotypes. Moreover, a significant proportion of cases studied by array will show a clinically significant CNA even with apparently normal karyotypes. © 2012 John Wiley & Sons, Ltd.