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CHD2 variants are a risk factor for photosensitivity in epilepsy
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 ence...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407192/ https://www.ncbi.nlm.nih.gov/pubmed/25783594 http://dx.doi.org/10.1093/brain/awv052 |
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author | Galizia, Elizabeth C. Myers, Candace T. Leu, Costin de Kovel, Carolien G. F. Afrikanova, Tatiana Cordero-Maldonado, Maria Lorena Martins, Teresa G. Jacmin, Maxime Drury, Suzanne Krishna Chinthapalli, V. Muhle, Hiltrud Pendziwiat, Manuela Sander, Thomas Ruppert, Ann-Kathrin Møller, Rikke S. Thiele, Holger Krause, Roland Schubert, Julian Lehesjoki, Anna-Elina Nürnberg, Peter Lerche, Holger Palotie, Aarno Coppola, Antonietta Striano, Salvatore Gaudio, Luigi Del Boustred, Christopher Schneider, Amy L. Lench, Nicholas Jocic-Jakubi, Bosanka Covanis, Athanasios Capovilla, Giuseppe Veggiotti, Pierangelo Piccioli, Marta Parisi, Pasquale Cantonetti, Laura Sadleir, Lynette G. Mullen, Saul A. Berkovic, Samuel F. Stephani, Ulrich Helbig, Ingo Crawford, Alexander D. Esguerra, Camila V. Kasteleijn-Nolst Trenité, Dorothee G. A. Koeleman, Bobby P. C. Mefford, Heather C. Scheffer, Ingrid E. Sisodiya, Sanjay M. |
author_facet | Galizia, Elizabeth C. Myers, Candace T. Leu, Costin de Kovel, Carolien G. F. Afrikanova, Tatiana Cordero-Maldonado, Maria Lorena Martins, Teresa G. Jacmin, Maxime Drury, Suzanne Krishna Chinthapalli, V. Muhle, Hiltrud Pendziwiat, Manuela Sander, Thomas Ruppert, Ann-Kathrin Møller, Rikke S. Thiele, Holger Krause, Roland Schubert, Julian Lehesjoki, Anna-Elina Nürnberg, Peter Lerche, Holger Palotie, Aarno Coppola, Antonietta Striano, Salvatore Gaudio, Luigi Del Boustred, Christopher Schneider, Amy L. Lench, Nicholas Jocic-Jakubi, Bosanka Covanis, Athanasios Capovilla, Giuseppe Veggiotti, Pierangelo Piccioli, Marta Parisi, Pasquale Cantonetti, Laura Sadleir, Lynette G. Mullen, Saul A. Berkovic, Samuel F. Stephani, Ulrich Helbig, Ingo Crawford, Alexander D. Esguerra, Camila V. Kasteleijn-Nolst Trenité, Dorothee G. A. Koeleman, Bobby P. C. Mefford, Heather C. Scheffer, Ingrid E. Sisodiya, Sanjay M. |
author_sort | Galizia, Elizabeth C. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4407192 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44071922015-06-26 CHD2 variants are a risk factor for photosensitivity in epilepsy Galizia, Elizabeth C. Myers, Candace T. Leu, Costin de Kovel, Carolien G. F. Afrikanova, Tatiana Cordero-Maldonado, Maria Lorena Martins, Teresa G. Jacmin, Maxime Drury, Suzanne Krishna Chinthapalli, V. Muhle, Hiltrud Pendziwiat, Manuela Sander, Thomas Ruppert, Ann-Kathrin Møller, Rikke S. Thiele, Holger Krause, Roland Schubert, Julian Lehesjoki, Anna-Elina Nürnberg, Peter Lerche, Holger Palotie, Aarno Coppola, Antonietta Striano, Salvatore Gaudio, Luigi Del Boustred, Christopher Schneider, Amy L. Lench, Nicholas Jocic-Jakubi, Bosanka Covanis, Athanasios Capovilla, Giuseppe Veggiotti, Pierangelo Piccioli, Marta Parisi, Pasquale Cantonetti, Laura Sadleir, Lynette G. Mullen, Saul A. Berkovic, Samuel F. Stephani, Ulrich Helbig, Ingo Crawford, Alexander D. Esguerra, Camila V. Kasteleijn-Nolst Trenité, Dorothee G. A. Koeleman, Bobby P. C. Mefford, Heather C. Scheffer, Ingrid E. Sisodiya, Sanjay M. Brain Original Articles 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. Oxford University Press 2015-05 2015-03-16 /pmc/articles/PMC4407192/ /pubmed/25783594 http://dx.doi.org/10.1093/brain/awv052 Text en © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. http://creativecommons.org/licenses/by/4.0/ 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. |
spellingShingle | Original Articles Galizia, Elizabeth C. Myers, Candace T. Leu, Costin de Kovel, Carolien G. F. Afrikanova, Tatiana Cordero-Maldonado, Maria Lorena Martins, Teresa G. Jacmin, Maxime Drury, Suzanne Krishna Chinthapalli, V. Muhle, Hiltrud Pendziwiat, Manuela Sander, Thomas Ruppert, Ann-Kathrin Møller, Rikke S. Thiele, Holger Krause, Roland Schubert, Julian Lehesjoki, Anna-Elina Nürnberg, Peter Lerche, Holger Palotie, Aarno Coppola, Antonietta Striano, Salvatore Gaudio, Luigi Del Boustred, Christopher Schneider, Amy L. Lench, Nicholas Jocic-Jakubi, Bosanka Covanis, Athanasios Capovilla, Giuseppe Veggiotti, Pierangelo Piccioli, Marta Parisi, Pasquale Cantonetti, Laura Sadleir, Lynette G. Mullen, Saul A. Berkovic, Samuel F. Stephani, Ulrich Helbig, Ingo Crawford, Alexander D. Esguerra, Camila V. Kasteleijn-Nolst Trenité, Dorothee G. A. Koeleman, Bobby P. C. Mefford, Heather C. Scheffer, Ingrid E. Sisodiya, Sanjay M. CHD2 variants are a risk factor for photosensitivity in epilepsy |
title | CHD2 variants are a risk factor for photosensitivity in epilepsy |
title_full | CHD2 variants are a risk factor for photosensitivity in epilepsy |
title_fullStr | CHD2 variants are a risk factor for photosensitivity in epilepsy |
title_full_unstemmed | CHD2 variants are a risk factor for photosensitivity in epilepsy |
title_short | CHD2 variants are a risk factor for photosensitivity in epilepsy |
title_sort | chd2 variants are a risk factor for photosensitivity in epilepsy |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407192/ https://www.ncbi.nlm.nih.gov/pubmed/25783594 http://dx.doi.org/10.1093/brain/awv052 |
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