CHD2 variants are a risk factor for photosensitivity in epilepsy

Elizabeth C. Galizia, Candace T. Myers, Costin Leu, Carolien G F De Kovel, Tatiana Afrikanova, Maria Lorena Cordero-Maldonado, Teresa G. Martins, Maxime Jacmin, Suzanne Drury, V. Krishna Chinthapalli, Hiltrud Muhle, Manuela Pendziwiat, Thomas Sander, Ann Kathrin Ruppert, Rikke S. Moller, Holger Thiele, Roland Krause, Julian Schubert, Anna Elina Lehesjoki, Peter Nürnberg & 27 others Holger Lerche, Aarno Palotie, Antonietta Coppola, Salvatore Striano, Luigi Del Gaudio, Christopher Boustred, Amy L. Schneider, Nicholas Lench, Bosanka Jocic-Jakubi, Athanasios Covanis, Giuseppe Capovilla, Pierangelo Veggiotti, Marta Piccioli, Pasquale Parisi, Laura Cantonetti, Lynette G. Sadleir, Saul A. Mullen, Samuel F. Berkovic, Ulrich Stephani, Ingo Helbig, Alexander D. Crawford, Camila V. Esguerra, Dorothee G A Kasteleijn Nolst Trenité, Bobby P C Koeleman, Heather C. Mefford, Ingrid E. Scheffer, Sanjay M. Sisodiya

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1198-1207
Number of pages10
JournalBrain
Volume138
Issue number5
DOIs
Publication statusPublished - May 1 2015

Fingerprint

Reflex Epilepsy
Epilepsy
Seizures
Exome
Generalized Epilepsy
Brain Diseases
Zebrafish
Eyelids
Mutation
Ion Channels
Larva
Electroencephalography
Risk Factors
Light
Research
Genes

Keywords

  • Eyelid myoclonia with absences
  • Photosensitive
  • Seizure

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Galizia, E. C., Myers, C. T., Leu, C., De Kovel, C. G. F., Afrikanova, T., Cordero-Maldonado, M. L., ... Sisodiya, S. M. (2015). CHD2 variants are a risk factor for photosensitivity in epilepsy. Brain, 138(5), 1198-1207. https://doi.org/10.1093/brain/awv028

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; Chinthapalli, V. Krishna; Muhle, Hiltrud; Pendziwiat, Manuela; Sander, Thomas; Ruppert, Ann Kathrin; Moller, Rikke S.; Thiele, Holger; Krause, Roland; Schubert, Julian; Lehesjoki, Anna Elina; Nürnberg, Peter; Lerche, Holger; Palotie, Aarno; Coppola, Antonietta; Striano, Salvatore; Del Gaudio, Luigi; 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.; Trenité, Dorothee G A Kasteleijn Nolst; Koeleman, Bobby P C; Mefford, Heather C.; Scheffer, Ingrid E.; Sisodiya, Sanjay M.

In: Brain, Vol. 138, No. 5, 01.05.2015, p. 1198-1207.

Research output: Contribution to journalArticle

Galizia, EC, Myers, CT, Leu, C, De Kovel, CGF, Afrikanova, T, Cordero-Maldonado, ML, Martins, TG, Jacmin, M, Drury, S, Chinthapalli, VK, Muhle, H, Pendziwiat, M, Sander, T, Ruppert, AK, Moller, RS, Thiele, H, Krause, R, Schubert, J, Lehesjoki, AE, Nürnberg, P, Lerche, H, Palotie, A, Coppola, A, Striano, S, Del Gaudio, L, Boustred, C, Schneider, AL, Lench, N, Jocic-Jakubi, B, Covanis, A, Capovilla, G, Veggiotti, P, Piccioli, M, Parisi, P, Cantonetti, L, Sadleir, LG, Mullen, SA, Berkovic, SF, Stephani, U, Helbig, I, Crawford, AD, Esguerra, CV, Trenité, DGAKN, Koeleman, BPC, Mefford, HC, Scheffer, IE & Sisodiya, SM 2015, 'CHD2 variants are a risk factor for photosensitivity in epilepsy', Brain, vol. 138, no. 5, pp. 1198-1207. https://doi.org/10.1093/brain/awv028
Galizia EC, Myers CT, Leu C, De Kovel CGF, Afrikanova T, Cordero-Maldonado ML et al. CHD2 variants are a risk factor for photosensitivity in epilepsy. Brain. 2015 May 1;138(5):1198-1207. https://doi.org/10.1093/brain/awv028
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 ; Chinthapalli, V. Krishna ; Muhle, Hiltrud ; Pendziwiat, Manuela ; Sander, Thomas ; Ruppert, Ann Kathrin ; Moller, Rikke S. ; Thiele, Holger ; Krause, Roland ; Schubert, Julian ; Lehesjoki, Anna Elina ; Nürnberg, Peter ; Lerche, Holger ; Palotie, Aarno ; Coppola, Antonietta ; Striano, Salvatore ; Del Gaudio, Luigi ; 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. ; Trenité, Dorothee G A Kasteleijn Nolst ; Koeleman, Bobby P C ; Mefford, Heather C. ; Scheffer, Ingrid E. ; Sisodiya, Sanjay M. / CHD2 variants are a risk factor for photosensitivity in epilepsy. In: Brain. 2015 ; Vol. 138, No. 5. pp. 1198-1207.
@article{8d9d095beb234b1c8852735ca1cd520d,
title = "CHD2 variants are a risk factor for photosensitivity in epilepsy",
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 = "Eyelid myoclonia with absences, Photosensitive, Seizure",
author = "Galizia, {Elizabeth C.} and Myers, {Candace T.} and Costin Leu and {De Kovel}, {Carolien G F} and Tatiana Afrikanova and Cordero-Maldonado, {Maria Lorena} and Martins, {Teresa G.} and Maxime Jacmin and Suzanne Drury and Chinthapalli, {V. Krishna} and Hiltrud Muhle and Manuela Pendziwiat and Thomas Sander and Ruppert, {Ann Kathrin} and Moller, {Rikke S.} and Holger Thiele and Roland Krause and Julian Schubert and Lehesjoki, {Anna Elina} and Peter N{\"u}rnberg and Holger Lerche and Aarno Palotie and Antonietta Coppola and Salvatore Striano and {Del Gaudio}, Luigi and Christopher Boustred and Schneider, {Amy L.} and Nicholas Lench and Bosanka Jocic-Jakubi and Athanasios Covanis and Giuseppe Capovilla and Pierangelo Veggiotti and Marta Piccioli and Pasquale Parisi and Laura Cantonetti and Sadleir, {Lynette G.} and Mullen, {Saul A.} and Berkovic, {Samuel F.} and Ulrich Stephani and Ingo Helbig and Crawford, {Alexander D.} and Esguerra, {Camila V.} and Trenit{\'e}, {Dorothee G A Kasteleijn Nolst} and Koeleman, {Bobby P C} and Mefford, {Heather C.} and Scheffer, {Ingrid E.} and Sisodiya, {Sanjay M.}",
year = "2015",
month = "5",
day = "1",
doi = "10.1093/brain/awv028",
language = "English",
volume = "138",
pages = "1198--1207",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - CHD2 variants are a risk factor for photosensitivity in epilepsy

AU - Galizia, Elizabeth C.

AU - Myers, Candace T.

AU - Leu, Costin

AU - De Kovel, Carolien G F

AU - Afrikanova, Tatiana

AU - Cordero-Maldonado, Maria Lorena

AU - Martins, Teresa G.

AU - Jacmin, Maxime

AU - Drury, Suzanne

AU - Chinthapalli, V. Krishna

AU - Muhle, Hiltrud

AU - Pendziwiat, Manuela

AU - Sander, Thomas

AU - Ruppert, Ann Kathrin

AU - Moller, Rikke S.

AU - Thiele, Holger

AU - Krause, Roland

AU - Schubert, Julian

AU - Lehesjoki, Anna Elina

AU - Nürnberg, Peter

AU - Lerche, Holger

AU - Palotie, Aarno

AU - Coppola, Antonietta

AU - Striano, Salvatore

AU - Del Gaudio, Luigi

AU - Boustred, Christopher

AU - Schneider, Amy L.

AU - Lench, Nicholas

AU - Jocic-Jakubi, Bosanka

AU - Covanis, Athanasios

AU - Capovilla, Giuseppe

AU - Veggiotti, Pierangelo

AU - Piccioli, Marta

AU - Parisi, Pasquale

AU - Cantonetti, Laura

AU - Sadleir, Lynette G.

AU - Mullen, Saul A.

AU - Berkovic, Samuel F.

AU - Stephani, Ulrich

AU - Helbig, Ingo

AU - Crawford, Alexander D.

AU - Esguerra, Camila V.

AU - Trenité, Dorothee G A Kasteleijn Nolst

AU - Koeleman, Bobby P C

AU - Mefford, Heather C.

AU - Scheffer, Ingrid E.

AU - Sisodiya, Sanjay M.

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

KW - Eyelid myoclonia with absences

KW - Photosensitive

KW - Seizure

UR - http://www.scopus.com/inward/record.url?scp=84929658567&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929658567&partnerID=8YFLogxK

U2 - 10.1093/brain/awv028

DO - 10.1093/brain/awv028

M3 - Article

VL - 138

SP - 1198

EP - 1207

JO - Brain

JF - Brain

SN - 0006-8950

IS - 5

ER -