{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:40:55Z","timestamp":1787618455510,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,23]],"date-time":"2023-12-23T00:00:00Z","timestamp":1703289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["INTER\/DFG\/21\/163"],"award-info":[{"award-number":["INTER\/DFG\/21\/163"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Epilepsy with eyelid myoclonia (EEM) spectrum is a generalized form of epilepsy characterized by eyelid myoclonia with or without absences, eye closure\u2010induced seizures with electroencephalographic paroxysms, and photosensitivity. Based on the specific clinical features, age at onset, and familial occurrence, a genetic cause has been postulated. Pathogenic variants in <jats:italic>CHD2<\/jats:italic>, <jats:italic>SYNGAP1<\/jats:italic>, <jats:italic>NEXMIF<\/jats:italic>, <jats:italic>RORB<\/jats:italic>, and <jats:italic>GABRA1<\/jats:italic> have been reported in individuals with photosensitivity and eyelid myoclonia, but whether other genes are also involved, or a single gene is uniquely linked with EEM, or its subtypes, is not yet known. We aimed to dissect the genetic etiology of EEM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied a cohort of 105 individuals by using whole exome sequencing. Individuals were divided into two groups: EEM\u2212 (isolated EEM) and EEM+ (EEM accompanied by intellectual disability [ID] or any other neurodevelopmental\/psychiatric disorder).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified nine variants classified as pathogenic\/likely pathogenic in the entire cohort (8.57%); among these, eight (five in <jats:italic>CHD2<\/jats:italic>, one in <jats:italic>NEXMIF<\/jats:italic>, one in <jats:italic>SYNGAP1<\/jats:italic>, and one in <jats:italic>TRIM8<\/jats:italic>) were found in the EEM+ subcohort (28.57%). Only one variant (<jats:italic>IFIH1<\/jats:italic>) was found in the EEM\u2212 subcohort (1.29%); however, because the phenotype of the proband did not fit with published data, additional evidence is needed before considering <jats:italic>IFIH1<\/jats:italic> variants and EEM\u2212 an established association. Burden analysis did not identify any single burdened gene or gene set.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Our results suggest that for EEM, as for many other epilepsies, the identification of a genetic cause is more likely with comorbid ID and\/or other neurodevelopmental disorders. Pathogenic variants were mostly found in <jats:italic>CHD2<\/jats:italic>, and the association of <jats:italic>CHD2<\/jats:italic> with EEM+ can now be considered a reasonable gene\u2013disease association. We provide further evidence to strengthen the association of EEM+ with <jats:italic>NEXMIF<\/jats:italic> and <jats:italic>SYNGAP1<\/jats:italic>. Possible new associations between EEM+ and <jats:italic>TRIM8<\/jats:italic>, and EEM\u2212 and <jats:italic>IFIH1<\/jats:italic>, are also reported. Although we provide robust evidence for gene variants associated with EEM+, the core genetic etiology of EEM\u2212 remains to be elucidated.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17859","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T08:44:57Z","timestamp":1702457097000},"page":"779-791","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Dissecting genetics of spectrum of epilepsies with eyelid myoclonia by exome sequencing"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4845-4293","authenticated-orcid":false,"given":"Antonietta","family":"Coppola","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Reproductive and Odontostomatological Sciences Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Krithika","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology  London UK"},{"name":"Chalfont Centre for Epilepsy  Chalfont St Peter UK"},{"name":"School of Life Sciences Anglia Ruskin University  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Iacomino","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dheeraj","family":"Bobbili","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Luxembourg Center for Systems Biomedicine  Belvaux Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5639-1969","authenticated-orcid":false,"given":"Simona","family":"Balestrini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology  London UK"},{"name":"Chalfont Centre for Epilepsy  Chalfont St Peter UK"},{"name":"Neuroscience Department Meyer Children's Hospital\u2013University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Bagnasco","sequence":"additional","affiliation":[{"name":"Division of Child Neuropsychiatry Martini Hospital  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonilda","family":"Bilo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Reproductive and Odontostomatological Sciences Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Buti","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit and Laboratories Meyer Children's Hospital\u2014University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Casellato","sequence":"additional","affiliation":[{"name":"Unit of Child Neuropsychiatry University Hospital of Sassari  Sassari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5118-5103","authenticated-orcid":false,"given":"Claudia","family":"Cuccurullo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Reproductive and Odontostomatological Sciences Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Ferlazzo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Regional Epilepsy Center Great Metropolitan Hospital, Bianchi\u2010Melacrino Morelli  Reggio Calabria Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costin","family":"Leu","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology  London UK"},{"name":"Genomic Medicine Institute, Lerner Research Institute Cleveland Clinic  Cleveland Ohio USA"},{"name":"Stanley Center of Psychiatric Research Broad Institute of Harvard and Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Giordano","sequence":"additional","affiliation":[{"name":"Unit of Child Neurology and Psychiatry ASST Spedali Civili di Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Gobbi","sequence":"additional","affiliation":[{"name":"Child Neurology Unit IRCCS Istituto delle Scienze Neurologiche  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Hernandez\u2010Hernandez","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology  London UK"},{"name":"Chalfont Centre for Epilepsy  Chalfont St Peter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Lench","sequence":"additional","affiliation":[{"name":"MRC Nucleic Acid Therapy Accelerator Research Complex at Harwell, Rutherford Appleton Laboratory  Harwell UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology  London UK"},{"name":"Chalfont Centre for Epilepsy  Chalfont St Peter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0334-539X","authenticated-orcid":false,"given":"Stefano","family":"Meletti","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic, and Neural Science University of Modena and Reggio Emilia  Modena Italy"},{"name":"Neurology Unit OCB Hospital, Azienda Ospedaliera Universitaria di Modena  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tullio","family":"Messana","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Neuropsichiatria Infantile  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Nigro","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5927-1185","authenticated-orcid":false,"given":"Michele","family":"Pinelli","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Pippucci","sequence":"additional","affiliation":[{"name":"Computational Genomics Unit IRCCS Azienda Ospedaliero\u2013Universitaria di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravishankara","family":"Bellampalli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology  London UK"},{"name":"Chalfont Centre for Epilepsy  Chalfont St Peter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Salis","sequence":"additional","affiliation":[{"name":"Unit of Child Neuropsychiatry ASST Fatebenefratelli Sacco  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito","family":"Sofia","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Advanced Technologies \u201cG.F. Ingrassia,\u201d Section of Neurosciences University of Catania  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6065-1476","authenticated-orcid":false,"given":"Pasquale","family":"Striano","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Muscular Diseases Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Striano","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Reproductive and Odontostomatological Sciences Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Tassi","sequence":"additional","affiliation":[{"name":"\u201cClaudio Munari\u201d Epilepsy Surgery Center Niguarda Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aglaia","family":"Vignoli","sequence":"additional","affiliation":[{"name":"Department of Health Sciences Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6280-7526","authenticated-orcid":false,"given":"Anna Elisabetta","family":"Vaudano","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic, and Neural Science University of Modena and Reggio Emilia  Modena Italy"},{"name":"Neurology Unit OCB Hospital, Azienda Ospedaliera Universitaria di Modena  Modena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Viri","sequence":"additional","affiliation":[{"name":"Department of Child Neurology and Psychiatry AOU Maggiore della Carit\u00e0 Novara  Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2311-2174","authenticated-orcid":false,"given":"Ingrid E.","family":"Scheffer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Austin Health, Epilepsy Research Center University of Melbourne  Heidelberg Victoria Australia"},{"name":"Florey Institute of Neuroscience and Mental Health  Heidelberg Victoria Australia"},{"name":"Murdoch Children's Research Institute and Department of Paediatrics Royal Children's Hospital, University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8698-3770","authenticated-orcid":false,"given":"Patrick","family":"May","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Luxembourg Center for Systems Biomedicine  Belvaux Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Zara","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics IRCCS Istituto Giannina Gaslini  Genoa Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1511-5893","authenticated-orcid":false,"given":"Sanjay M.","family":"Sisodiya","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology  London UK"},{"name":"Chalfont Centre for Epilepsy  Chalfont St Peter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,23]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1977.tb08014.x"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17241"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.56.12.1312"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200165"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.15157"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17683"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-200x.2005.02065.x"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.02002.x"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03692.x"},{"key":"e_1_2_15_11_1","first-page":"3","article-title":"Photosensitivity in epilepsy. Electrophysiological and clinical correlates","volume":"125","author":"Kasteleijn\u2010Nolst Trenite DG","year":"1989","journal-title":"Acta Neurol Scand Suppl"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20500"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12439"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.09.017"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001305"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2014.06.003"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv052"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103451"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006729"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-00988-9"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.80"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000003087"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2611"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035790"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0528-2"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-0337"},{"key":"e_1_2_15_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13760-018-0887-y"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17166"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.722664"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40357"},{"key":"e_1_2_15_35_1","first-page":"3440","article-title":"TRIM8 inhibits breast cancer proliferation by regulating estrogen signaling","volume":"10","author":"Tian Z","year":"2020","journal-title":"Am J Cancer Res"},{"key":"e_1_2_15_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2014.02.005"},{"key":"e_1_2_15_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-020-0610-3"},{"key":"e_1_2_15_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2020.1713101"},{"key":"e_1_2_15_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-021-01121-7"},{"key":"e_1_2_15_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2017.09.001"},{"key":"e_1_2_15_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2021.01.008"},{"key":"e_1_2_15_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/ahg.12157"},{"key":"e_1_2_15_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.09.002"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.17859","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T16:46:47Z","timestamp":1747673207000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.17859"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,23]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1111\/epi.17859"],"URL":"https:\/\/doi.org\/10.1111\/epi.17859","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,23]]},"assertion":[{"value":"2023-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}