{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:52:33Z","timestamp":1791273153600,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T00:00:00Z","timestamp":1515369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["We4896\/3\u20101"],"award-info":[{"award-number":["We4896\/3\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["He5415\/6\u20101"],"award-info":[{"award-number":["He5415\/6\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Pathogenic <jats:italic>SLC6A1<\/jats:italic> variants were recently described in patients with myoclonic atonic epilepsy (MAE) and intellectual disability (ID). We set out to define the phenotypic spectrum in a larger cohort of <jats:italic>SCL6A1<\/jats:italic>\u2010mutated patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We collected 24 <jats:italic>SLC6A1<\/jats:italic> probands and 6 affected family members. Four previously published cases were included for further electroclinical description. In total, we reviewed the electroclinical data of 34 subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Cognitive development was impaired in 33\/34 (97%) subjects; 28\/34 had mild to moderate ID, with language impairment being the most common feature. Epilepsy was diagnosed in 31\/34 cases with mean onset at 3.7\u00a0years. Cognitive assessment before epilepsy onset was available in 24\/31 subjects and was normal in 25% (6\/24), and consistent with mild ID in 46% (11\/24) or moderate ID in 17% (4\/24). Two patients had speech delay only, and 1 had severe ID. After epilepsy onset, cognition deteriorated in 46% (11\/24) of cases. The most common seizure types were absence, myoclonic, and atonic seizures. Sixteen cases fulfilled the diagnostic criteria for MAE. Seven further patients had different forms of generalized epilepsy and 2 had focal epilepsy. Twenty of 31 patients became seizure\u2010free, with valproic acid being the most effective drug. There was no clear\u2010cut correlation between seizure control and cognitive outcome. Electroencephalography (EEG) findings were available in 27\/31 patients showing irregular bursts of diffuse 2.5\u20103.5\u00a0Hz spikes\/polyspikes\u2010and\u2010slow waves in 25\/31. Two patients developed an EEG pattern resembling electrical status epilepticus during sleep. Ataxia was observed in 7\/34 cases. We describe 7 truncating and 18 missense variants, including 4 recurrent variants (Gly232Val, Ala288Val, Val342Met, and Gly362Arg).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Most patients carrying pathogenic <jats:italic>SLC6A1<\/jats:italic> variants have an MAE phenotype with language delay and mild\/moderate ID before epilepsy onset. However, ID alone or associated with focal epilepsy can also be observed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.13986","type":"journal-article","created":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T05:54:07Z","timestamp":1515563647000},"page":"389-402","source":"Crossref","is-referenced-by-count":150,"title":["Defining the phenotypic spectrum of <i>SLC6A1<\/i> mutations"],"prefix":"10.1111","volume":"59","author":[{"given":"Katrine M.","family":"Johannesen","sequence":"first","affiliation":[{"name":"The Danish Epilepsy Center Filadelfia Dianalund Denmark"},{"name":"Institute for Regional Health Services Research University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Gardella","sequence":"additional","affiliation":[{"name":"The Danish Epilepsy Center Filadelfia Dianalund Denmark"},{"name":"Institute for Regional Health Services Research University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarja","family":"Linnankivi","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Children's Hospital Helsinki University Hospital Helsinki University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Courage","sequence":"additional","affiliation":[{"name":"The Folkh\u00e4lsan Institute of Genetics University of Helsinki Helsinki Finland"},{"name":"Research Programs Unit Molecular Neurology and Neuroscience Center Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"de Saint Martin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Pediatric Neurology University Hospital of Strasbourg Strasbourg France"},{"name":"Reference Center for Rare Epilepsies Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna\u2010Elina","family":"Lehesjoki","sequence":"additional","affiliation":[{"name":"The Folkh\u00e4lsan Institute of Genetics University of Helsinki Helsinki Finland"},{"name":"Research Programs Unit Molecular Neurology and Neuroscience Center Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyril","family":"Mignot","sequence":"additional","affiliation":[{"name":"Department of Genetics Center for Rare causes of Intellectual Disabilities and UPMC Research Group \u201cIntellectual Disabilities and Autism\u201d Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Afenjar","sequence":"additional","affiliation":[{"name":"APHP, Genetic Services Hospital Trousseau Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetan","family":"Lesca","sequence":"additional","affiliation":[{"name":"Departments of Genetics Lyon University Hospitals Lyon France"},{"name":"Claude Bernard Lyon I University Lyon France"},{"name":"Lyon Neuroscience Research Center CNRS UMRS5292 INSERM U1028 Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Th\u00e9r\u00e8se","family":"Abi\u2010Warde","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Pediatric Neurology University Hospital of Strasbourg Strasbourg France"},{"name":"Reference Center for Rare Epilepsies Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamel","family":"Chelly","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Neurogenetics Institut G\u00e9n\u00e9tique Biologie Mol\u00e9culaire Cellulaire (IGBMC) Illkirch France"},{"name":"Laboratory of Genetic Diagnosis H\u00f4pitaux Universitaires de Strasbourg Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lie","family":"Piton","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Neurogenetics Institut G\u00e9n\u00e9tique Biologie Mol\u00e9culaire Cellulaire (IGBMC) Illkirch France"},{"name":"Laboratory of Genetic Diagnosis H\u00f4pitaux Universitaires de Strasbourg Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"II","given":"J. 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