{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:14:55Z","timestamp":1790313295688,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,12,8]],"date-time":"2014-12-08T00:00:00Z","timestamp":1417996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ns27941"],"award-info":[{"award-number":["ns27941"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ns70323"],"award-info":[{"award-number":["ns70323"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ns61829"],"award-info":[{"award-number":["ns61829"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2015,2]]},"abstract":"Summary<\/jats:title>\n \n Objective<\/jats:title>\n \n Screening for specific coding mutations in the\n \n EFHC<\/jats:styled-content>\n 1\n <\/jats:italic>\n gene has been proposed as a means of assessing susceptibility to juvenile myoclonic epilepsy (\n JME<\/jats:styled-content>\n ). To clarify the role of these mutations, especially those reported to be highly penetrant, we sought to measure the frequency of exonic\n \n EFHC<\/jats:styled-content>\n 1\n <\/jats:italic>\n mutations across multiple population samples.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n To find and test variants of large effect, we sequenced all\n \n EFHC<\/jats:styled-content>\n 1\n <\/jats:italic>\n exons in 23\n JME<\/jats:styled-content>\n and 23 non\u2010\n JME<\/jats:styled-content>\n idiopathic generalized epilepsy (\n IGE<\/jats:styled-content>\n ) Hispanic patients, and 60 matched controls. We also genotyped specific\n \n EFHC<\/jats:styled-content>\n 1\n <\/jats:italic>\n variants in\n IGE<\/jats:styled-content>\n cases and controls from multiple ethnic backgrounds, including 17 African American\n IGE<\/jats:styled-content>\n patients, with 24 matched controls, and 92 Caucasian\n JME<\/jats:styled-content>\n patients with 103 matched controls. These variants are reported to be pathogenic, but are also found among unphenotyped individuals in public databases. All subjects were from the New York City metro area and all controls were required to have no family history of seizures.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We found the reportedly pathogenic\n \n EFHC<\/jats:styled-content>\n 1\n P<\/jats:styled-content>\n 77\n T<\/jats:styled-content>\n \u2010\n R<\/jats:styled-content>\n 221\n H<\/jats:styled-content>\n <\/jats:italic>\n (rs149055334\u2010rs79761183)\n JME<\/jats:styled-content>\n haplotype in one Hispanic control and in two African American controls. Public databases also show that the\n \n EFHC<\/jats:styled-content>\n 1\n P<\/jats:styled-content>\n 77\n T<\/jats:styled-content>\n \u2010\n R<\/jats:styled-content>\n 221\n H<\/jats:styled-content>\n <\/jats:italic>\n JME<\/jats:styled-content>\n haplotype is present in unphenotyped West African ancestry populations, and we show that it can be found at appreciable frequency in healthy individuals with no family history of epilepsy. We also found a novel splice\u2010site mutation in a single Hispanic\n JME<\/jats:styled-content>\n patient, the effect of which is unknown.\n <\/jats:p>\n <\/jats:sec>\n \n Significance<\/jats:title>\n \n Our findings raise questions about the effect of reportedly pathogenic\n \n EFHC<\/jats:styled-content>\n 1\n <\/jats:italic>\n mutations on\n JME<\/jats:styled-content>\n . One intriguing possibility is that some\n \n EFHC<\/jats:styled-content>\n 1\n <\/jats:italic>\n mutations may be pathogenic only when introduced into specific genetic backgrounds. By focusing on data from multiple populations, including the understudied Hispanic and Black\/African American populations, our study highlights that for complex traits like\n JME<\/jats:styled-content>\n , the body of evidence necessary to infer causality is high.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/epi.12864","type":"journal-article","created":{"date-parts":[[2014,12,9]],"date-time":"2014-12-09T06:07:17Z","timestamp":1418105237000},"page":"188-194","source":"Crossref","is-referenced-by-count":22,"title":["Pathogenic\n \n EFHC<\/scp>\n 1\n <\/i>\n mutations are tolerated in healthy individuals dependent on reported ancestry"],"prefix":"10.1111","volume":"56","author":[{"given":"Ryan L.","family":"Subaran","sequence":"first","affiliation":[{"name":"Nationwide Children's Hospital Research Institute The Ohio State University Columbus Ohio U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette M.","family":"Conte","sequence":"additional","affiliation":[{"name":"Mailman School of Public Health Columbia University New York New York U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C. L.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Nationwide Children's Hospital Research Institute The Ohio State University Columbus Ohio U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Nationwide Children's Hospital Research Institute The Ohio State University Columbus Ohio U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2012.06.034"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10724"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19960614)63:3<438::AID-AJMG5>3.0.CO;2-N"},{"key":"e_1_2_7_5_1","first-page":"368","article-title":"Juvenile myoclonic epilepsy locus in chromosome 6p21.2\u2010p11: linkage to convulsions and electroencephalography trait","volume":"57","author":"Liu AW","year":"1995","journal-title":"Am J Hum Genet"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2004.36003.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410390208"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1393"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000313149.73035.99"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp006"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2390"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds356"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2006.00676.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1994.0012"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000250254.67042.1b"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0198-53"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0198-25"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01762.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2006.06.038"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3109\/01677063.2013.772176"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2009.02429.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20178"},{"key":"e_1_2_7_23_1","volume-title":"Jasper's basic mechanisms of the epilepsies","author":"Grisar T"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2009.11.009"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02734.x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1086\/518564"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1086\/302763"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000481"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1086\/519795"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001111"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002410"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1251688"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1975.tb04721.x"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-010-0831-6"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199910)46:4<671::AID-ANA20>3.0.CO;2-5"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000649"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl019"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm248"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.11.016"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03536.x"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.12864","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.12864","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.12864","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.12864","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T05:28:36Z","timestamp":1696224516000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.12864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,8]]},"references-count":40,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,2]]}},"alternative-id":["10.1111\/epi.12864"],"URL":"https:\/\/doi.org\/10.1111\/epi.12864","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,8]]}}}