CHD2 variants are a risk factor for photosensitivity in epilepsy.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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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, EuroEPINOMICS CoGIE Consortium, 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
Аннотация
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.