CRITICAL REVIEW AND INVITED COMMENTARY
Epilepsy and the new cytogenetics
Article first published online: 26 JAN 2011
Wiley Periodicals, Inc. © 2011 International League Against Epilepsy
Volume 52, Issue 3, pages 423–432, March 2011
How to Cite
Mulley, J. C. and Mefford, H. C. (2011), Epilepsy and the new cytogenetics. Epilepsia, 52: 423–432. doi: 10.1111/j.1528-1167.2010.02932.x
- Issue published online: 11 MAR 2011
- Article first published online: 26 JAN 2011
- Accepted October 26, 2010; Early View publication January 26, 2011.
- Copy number variant (CNV);
We set out to review the extent to which molecular karyotyping has overtaken conventional cytogenetics in applications related to epilepsy. Multiplex ligase-dependent probe amplification (MLPA) targeted to predetermined regions such as SCN1A and KCNQ2 has been effectively applied over the last half a decade, and oligonucleotide array comparative genome hybridization (array CGH) is now well established for genome-wide exploration of microchromosomal variation. Array CGH is applicable to the characterization of lesions present in both sporadic and familial epilepsy, especially where clinical features of affected cases depart from established syndromes. Copy number variants (CNVs) associated with epilepsy and a range of other syndromes and conditions can be recurrent due to nonallelic homologous recombination in regions of segmental duplication. The most common of the recurrent microdeletions associated with generalized epilepsy are typically seen at a frequency of ∼1% at 15q13.3, 16p13.11, and 15q11.2, sites that also confer susceptibility for intellectual disability, autism, and schizophrenia. Incomplete penetrance and variable expressivity confound the established rules of cytogenetics for determining the pathogenicity for novel CNVs; however, as knowledge is gained for each of the recurrent CNVs, this is translated to genetic counseling. CNVs play a significant role in the susceptibility profile for epilepsies, with complex genetics and their comorbidities both from the “hotspots” defined by segmental duplication and elsewhere in the genome where their location and size are often novel.