How to cite this article: Bruno DL, Burgess T, Ren H, Nouri S, Pertile MD, Francis DI, Norris F, Kenney BK, Schouten J, Choo KHA, Slater HR. 2006. High-throughput analysis of chromosome abnormality in spontaneous miscarriage using an MLPA subtelomere assay with an ancillary FISH test for polyploidy. Am J Med Genet Part A 140A:2786–2793.
High-throughput analysis of chromosome abnormality in spontaneous miscarriage using an MLPA subtelomere assay with an ancillary FISH test for polyploidy†
Article first published online: 14 NOV 2006
Copyright © 2006 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 140A, Issue 24, pages 2786–2793, 15 December 2006
How to Cite
Bruno, D. L., Burgess, T., Ren, H., Nouri, S., Pertile, M. D., Francis, D. I., Norris, F., Kenney, B. K., Schouten, J., Andy Choo, K.H. and Slater, H. R. (2006), High-throughput analysis of chromosome abnormality in spontaneous miscarriage using an MLPA subtelomere assay with an ancillary FISH test for polyploidy. Am. J. Med. Genet., 140A: 2786–2793. doi: 10.1002/ajmg.a.31552
- Issue published online: 21 NOV 2006
- Article first published online: 14 NOV 2006
- Manuscript Accepted: 29 SEP 2006
- Manuscript Received: 10 JUN 2006
- prenatal diagnosis;
- spontaneous miscarriage;
Chromosome analysis of spontaneous miscarriages is clinically important but is hampered by frequent tissue culture failure and relatively low-resolution analysis. We have investigated replacement of conventional karyotype analysis with a quantitative subtelomere assay performed on uncultured tissue samples, which is based on Multiplex Ligation-Dependent Probe Amplification. This assay is suitable for this purpose as approximately 98% of all observed karyotype abnormalities in spontaneous miscarriages involve copy-number change to one or more subtelomere regions. A pilot study has compared karyotyping and subtelomere analysis on 78 samples. Extensive tissue necrosis accounted for failure of both karyotyping and subtelomere testing in four (5.1%) samples. Excluding these, there were no (0/74) subtelomere test failures compared to 9.5% (7/74) karyotype failures. Twenty-two (30%) whole chromosome aneuploidies and five (6.8%) structural abnormalities were detected using the subtelomere assay. With the exception of three cases of triploidy, all karyotype abnormalities were detected by the subtelomere assay. Following on from this study, a further 100 samples were tested using the subtelomere assay in conjunction with a simple ancillary FISH test using uncultured cells to exclude polyploidy in the event of a normal subtelomere assay result. Except for three necrotic samples, tests results were obtained for all cases revealing 18 abnormalities including one case of triploidy. Taking into consideration the high success rate for the combined MLPA and FISH test results, and the very significant additional advantages of cost-effective, high-throughput batching, and automated, objective analysis, this approach greatly facilitates routine investigation of chromosome abnormalities in spontaneous miscarriage. © 2006 Wiley-Liss, Inc.