{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:13:15Z","timestamp":1791349995408,"version":"4.3.1"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,5,14]],"date-time":"2014-05-14T00:00:00Z","timestamp":1400025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Childrens Fund for Health, Childrens University Hospital, Temple Street","award":["PAC 11-49"],"award-info":[{"award-number":["PAC 11-49"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To establish the genetic basis of\n                      <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>\n                      andau\u2010\n                      <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>\n                      leffner syndrome (\n                      <jats:styled-content style=\"fixed-case\">LKS<\/jats:styled-content>\n                      ) in a cohort of two discordant monozygotic (\n                      <jats:styled-content style=\"fixed-case\">MZ<\/jats:styled-content>\n                      ) twin pairs and 11 isolated cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used a multifaceted approach to identify genetic risk factors for\n                      <jats:styled-content style=\"fixed-case\">LKS<\/jats:styled-content>\n                      . Array comparative genomic hybridization (CGH) was performed using the\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      gilent 180K array. Whole genome methylation profiling was undertaken in the two discordant twin pairs, three isolated\n                      <jats:styled-content style=\"fixed-case\">LKS<\/jats:styled-content>\n                      cases, and 12 control samples using the\n                      <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>\n                      llumina 27K array. Exome sequencing was undertaken in 13 patients with\n                      <jats:styled-content style=\"fixed-case\">LKS<\/jats:styled-content>\n                      including two sets of discordant\n                      <jats:styled-content style=\"fixed-case\">MZ<\/jats:styled-content>\n                      twins. Data were analyzed with respect to novel and rare variants, overlapping genes, variants in reported epilepsy genes, and pathway enrichment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A variant (c\n                      <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>\n                      1553\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      ) was found in a single patient in the\n                      <jats:italic>GRIN2A<\/jats:italic>\n                      gene, causing an arginine to histidine change at site 518, a predicted glutamate binding site. Following copy number variation (\n                      <jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>\n                      ), methylation, and exome sequencing analysis, no single candidate gene was identified to cause\n                      <jats:styled-content style=\"fixed-case\">LKS<\/jats:styled-content>\n                      in the remaining cohort. However, a number of interesting additional candidate variants were identified including variants in\n                      <jats:italic>RELN<\/jats:italic>\n                      ,\n                      <jats:italic>BSN, EPHB2,<\/jats:italic>\n                      and\n                      <jats:italic>NID2<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      A single mutation was identified in the\n                      <jats:italic>GRIN2A<\/jats:italic>\n                      gene. This study has identified a number of additional candidate genes including\n                      <jats:italic>RELN<\/jats:italic>\n                      ,\n                      <jats:italic>BSN<\/jats:italic>\n                      ,\n                      <jats:italic>EPHB2,<\/jats:italic>\n                      and\n                      <jats:italic>NID2<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:p>\n                      A PowerPoint slide summarizing this article is available for download in the Supporting Information section\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.12645\/suppinfo\">here<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  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and Medical Science University College Dublin Dublin Ireland"},{"name":"School of Agriculture and Food Science University College Dublin Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dara","family":"McCreary","sequence":"additional","affiliation":[{"name":"Department of Neurology Children's University Hospital Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naisha","family":"Shah","sequence":"additional","affiliation":[{"name":"School of Medicine and Medical Science University College Dublin Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Collins","sequence":"additional","affiliation":[{"name":"Royal Children's Hospital Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bronwyn","family":"Parry\u2010Fielder","sequence":"additional","affiliation":[{"name":"Royal Children's Hospital Melbourne VIC 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