{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:30:07Z","timestamp":1790476207936,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,7,11]],"date-time":"2021-07-11T00:00:00Z","timestamp":1625961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005440","name":"Center for Scientific Review","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Develop Med Child Neuro"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>To determine whether genes that cause developmental and epileptic encephalopathies (DEEs) are more commonly implicated in intellectual disability with epilepsy as a comorbid feature than in intellectual disability only.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We performed targeted resequencing of 18 genes commonly implicated in DEEs in a cohort of 830 patients with intellectual disability (59% male) and 393 patients with DEEs (52% male).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed a significant enrichment of pathogenic\/likely pathogenic variants in patients with epilepsy and intellectual disability (16 out of 159 in seven genes) compared with intellectual disability only (2 out of 671) (<jats:italic>p<\/jats:italic>&lt;1.86\u00d710<jats:sup>\u221210<\/jats:sup>, odds ratio 37.22, 95% confidence interval 8.60\u2013337.0).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We identified seven genes that are more likely to cause epilepsy and intellectual disability than intellectual disability only. Conversely, two genes, <jats:italic>GRIN2B<\/jats:italic> and <jats:italic>SCN2A<\/jats:italic>, can be implicated in intellectual disability without epilepsy; in these instances intellectual disability is not a secondary consequence of ongoing seizures but rather a primary cause.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"box\" position=\"anchor\"><jats:caption><jats:title>What this paper adds<\/jats:title><\/jats:caption><jats:p>\n<jats:list list-type=\"bullet\">\n\n<jats:list-item><jats:p>A subset of genes are more commonly implicated in epilepsy than other neurodevelopmental disorders.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p><jats:italic>GRIN2B<\/jats:italic> and <jats:italic>SCN2A<\/jats:italic> are implicated in intellectual disability and epilepsy independently.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/dmcn.14989","type":"journal-article","created":{"date-parts":[[2021,7,11]],"date-time":"2021-07-11T17:49:45Z","timestamp":1626025785000},"page":"1441-1447","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic convergence of developmental and epileptic encephalopathies and intellectual disability"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4945-3628","authenticated-orcid":false,"given":"Gemma L","family":"Carvill","sequence":"first","affiliation":[{"name":"Department of Neurology Northwestern University Feinberg School of Medicine Chicago IL USA"},{"name":"Department of Pharmacology Northwestern University Feinberg School of Medicine Chicago IL USA"},{"name":"Department of Pediatrics Northwestern University Feinberg School of Medicine Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Lacroix","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Department of Pediatrics University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Zemel","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Department of Pediatrics University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Mehaffey","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Department of Pediatrics University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"De Vries","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han G","family":"Brunner","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center Nijmegen the Netherlands"},{"name":"Department of Clinical Genetics and GROW\u2010School for Oncology and Developmental Biology Maastricht University Medical Center Maastricht the Netherlands"}],"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":"Murdoch Children\u2019s Research and Florey Institutes Austin and Royal Children\u2019s Hospital University of Melbourne Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert B A","family":"De Vries","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisenka E L M","family":"Vissers","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7188-522X","authenticated-orcid":false,"given":"Heather C","family":"Mefford","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Department of Pediatrics University of Washington Seattle WA USA"},{"name":"Center for Pediatric Neurological Disease Research St. Jude Children\u2019s Research Hospital Memphis TN 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