High-resolution molecular karyotyping in patients with developmental delay and/or multiple congenital anomalies in a clinical setting
Article first published online: 8 APR 2010
© 2010 John Wiley & Sons A/S
Volume 79, Issue 2, pages 147–157, February 2011
How to Cite
Wincent, J., Anderlid, B.-M., Lagerberg, M., Nordenskjöld, M. and Schoumans, J. (2011), High-resolution molecular karyotyping in patients with developmental delay and/or multiple congenital anomalies in a clinical setting. Clinical Genetics, 79: 147–157. doi: 10.1111/j.1399-0004.2010.01442.x
- Issue published online: 8 APR 2010
- Article first published online: 8 APR 2010
- Received 22 January 2010, revised and accepted for publication 29 March 2010
- developmental delay;
- multiple congenital anomalies
Wincent J, Anderlid B-M, Lagerberg M, Nordenskjöld M, Schoumans J. High-resolution molecular karyotyping in patients with developmental delay and/or multiple congenital anomalies in a clinical setting.
Microarray-based comparative genomic hybridization (array-CGH) enables genomewide investigation of copy-number changes at high resolution and has recently been implemented as a clinical diagnostic tool. In this study we evaluate the usefulness of high-resolution arrays as a diagnostic tool in our laboratory and investigate the diagnostic yield in the first 160 patients who were clinically referred for investigation of developmental delay (DD)/multiple congenital anomalies (MCA). During this period both 38K BAC-arrays and 244K oligonucleotide-arrays were used. Copy-number variations (CNVs) not previously reported as normal variants were detected in 22.5% of cases. In 13.1% the aberrations were considered causal to the phenotype and in 9.4% the clinical significance was uncertain. There was no difference in diagnostic yield between patients with mild, moderate or severe DD. Although the effective resolution of the 244K oligonucleotide-arrays was higher than the 38K BAC-array, the diagnostic yield of both platforms was approximately equal and no causal aberrations <300 kb were detected in this patient cohort. We experienced that increasing the resolution of a whole genome screen in the diagnostic setting has its drawback of detecting an increased number of CNVs with uncertain contribution to a phenotype. Based on our experiences, array-CGH is recommended as the first-step analysis in the genetic evaluation of patients with DD and/or MCA.