![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
|
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
515kB | |
![[img]](http://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Material)
770kB |
| Item Type: | Article |
|---|---|
| Title: | CHD2 variants are a risk factor for photosensitivity in epilepsy |
| Creators Name: | Galizia, E.C. and Myers, C.T. and Leu, C. and de Kovel, C.G.F. and Afrikanova, T. and Cordero-Maldonado, M.L. and Martins, T.G. and Jacmin, M. and Drury, S. and Krishna Chinthapalli, V. and Muhle, H. and Pendziwiat, M. and Sander, T. and Ruppert, A.K. and Møller, R.S. and Thiele, H. and Krause, R. and Schubert, J. and Lehesjoki, A.E. and Nürnberg, P. and Lerche, H. and Palotie, A. and Coppola, A. and Striano, S. and Gaudio, L.D. and Boustred, C. and Schneider, A.L. and Lench, N. and Jocic-Jakubi, B. and Covanis, A. and Capovilla, G. and Veggiotti, P. and Piccioli, M. and Parisi, P. and Cantonetti, L. and Sadleir, L.G. and Mullen, S.A. and Berkovic, S.F and Stephani, U. and Helbig, I. and Crawford, A.D. and Esguerra, C.V. and Kasteleijn-Nolst Trenité, D.G.A. and Koeleman, B.P.C. and Mefford, H.C. and Scheffer, I.E. and Sisodiya, S.M. |
| Abstract: | Photosensitivity is a heritable abnormal cortical response to flickering light, manifesting as particular electroencephalographic changes, with or without seizures. Photosensitivity is prominent in a very rare epileptic encephalopathy due to de novo CHD2 mutations, but is also seen in epileptic encephalopathies due to other gene mutations. We determined whether CHD2 variation underlies photosensitivity in common epilepsies, specific photosensitive epilepsies and individuals with photosensitivity without seizures. We studied 580 individuals with epilepsy and either photosensitive seizures or abnormal photoparoxysmal response on electroencephalography, or both, and 55 individuals with photoparoxysmal response but no seizures. We compared CHD2 sequence data to publicly available data from 34 427 individuals, not enriched for epilepsy. We investigated the role of unique variants seen only once in the entire data set. We sought CHD2 variants in 238 exomes from familial genetic generalized epilepsies, and in other public exome data sets. We identified 11 unique variants in the 580 individuals with photosensitive epilepsies and 128 unique variants in the 34 427 controls: unique CHD2 variation is over-represented in cases overall (P = 2.17 × 10(-5)). Among epilepsy syndromes, there was over-representation of unique CHD2 variants (3/36 cases) in the archetypal photosensitive epilepsy syndrome, eyelid myoclonia with absences (P = 3.50 × 10(-4)). CHD2 variation was not over-represented in photoparoxysmal response without seizures. Zebrafish larvae with chd2 knockdown were tested for photosensitivity. Chd2 knockdown markedly enhanced mild innate zebrafish larval photosensitivity. CHD2 mutation is the first identified cause of the archetypal generalized photosensitive epilepsy syndrome, eyelid myoclonia with absences. Unique CHD2 variants are also associated with photosensitivity in common epilepsies. CHD2 does not encode an ion channel, opening new avenues for research into human cortical excitability. |
| Keywords: | Photosensitive, Seizure, Eyelid Myoclonia With Absences, Animals, Zebrafish |
| Source: | Brain |
| ISSN: | 0006-8950 |
| Publisher: | Oxford University Press |
| Volume: | 138 |
| Number: | 5 |
| Page Range: | 1198-1207 |
| Date: | May 2015 |
| Additional Information: | Janine Altmüller is member of the EuroEPINOMICS CoGIE Consortium. - Copyright © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Official Publication: | https://doi.org/10.1093/brain/awv052 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
Download Statistics
Download Statistics
