The authors have no conflict of interest to declare.
Pathogenic or not? Assessing the clinical relevance of copy number variants
Article first published online: 21 AUG 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Special Issue: Variant
Volume 84, Issue 5, pages 415–421, November 2013
How to Cite
Pathogenic or not? Assessing the clinical relevance of copy number variants., , , .
- Issue published online: 17 OCT 2013
- Article first published online: 21 AUG 2013
- Accepted manuscript online: 29 JUL 2013 07:20AM EST
- Manuscript Revised: 24 JUL 2013
- Manuscript Accepted: 24 JUL 2013
- Manuscript Received: 27 JUN 2013
- European Research Council. Grant Number: DENOVO 281964
- clinically relevant;
- copy number variation;
The availability of commercially produced genomic microarrays has resulted in the wide spread implementation of genomic microarrays, often as a first-tier diagnostic test for copy number variant (CNV) screening of patients who are suspected for chromosomal aberrations. Patients with intellectual disability (ID) and/or multiple congenital anomalies (MCA) were traditionally the main focus for this microarray-based CNV screening, but the application of microarrays to other (neurodevelopmental) disorders and tumor diagnostics has also been explored and implemented. The diagnostic workflow for patients with ID is now well established, relying on the identification of rare CNVs and determining their inheritance patterns. However, experience gained through screening large numbers of samples has revealed many subtleties and complexities of CNV interpretation. This has resulted in a better understanding of the contribution of CNVs to genomic disorders not only via de novo occurrence, but also via X-linked and recessive inheritance models as well as through models taking into account mosaicisms, imprinting, and digenic inheritance. In this review, we discuss CNV interpretation within the context of these different genetic disease models and common pitfalls that can occur when searching for supportive evidence that a CNV is clinically relevant.