{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:53:51Z","timestamp":1792803231783,"version":"4.5.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Disease-causing variants in STXBP1 are among the most common genetic causes of neurodevelopmental disorders. However, the phenotypic spectrum in STXBP1-related disorders is wide and clear correlations between variant type and clinical features have not been observed so far.<\/jats:p>\n                  <jats:p>Here, we harmonized clinical data across 534 individuals with STXBP1-related disorders and analysed 19\u200a973 derived phenotypic terms, including phenotypes of 253 individuals previously unreported in the scientific literature. The overall phenotypic landscape in STXBP1-related disorders is characterized by neurodevelopmental abnormalities in 95% and seizures in 89% of individuals, including focal-onset seizures as the most common seizure type (47%). More than 88% of individuals with STXBP1-related disorders have seizure onset in the first year of life, including neonatal seizure onset in 47%. Individuals with protein-truncating variants and deletions in STXBP1 (n = 261) were almost twice as likely to present with West syndrome and were more phenotypically similar than expected by chance. Five genetic hotspots with recurrent variants were identified in more than 10 individuals, including p.Arg406Cys\/His (n = 40), p.Arg292Cys\/His\/Leu\/Pro (n = 30), p.Arg551Cys\/Gly\/His\/Leu (n = 24), p.Pro139Leu (n = 12), and p.Arg190Trp (n = 11). None of the recurrent variants were significantly associated with distinct electroclinical syndromes, single phenotypic features, or showed overall clinical similarity, indicating that the baseline variability in STXBP1-related disorders is too high for discrete phenotypic subgroups to emerge. We then reconstructed the seizure history in 62 individuals with STXBP1-related disorders in detail, retrospectively assigning seizure type and seizure frequency monthly across 4433 time intervals, and retrieved 251 anti-seizure medication prescriptions from the electronic medical records. We demonstrate a dynamic pattern of seizure control and complex interplay with response to specific medications particularly in the first year of life when seizures in STXBP1-related disorders are the most prominent. Adrenocorticotropic hormone and phenobarbital were more likely to initially reduce seizure frequency in infantile spasms and focal seizures compared to other treatment options, while the ketogenic diet was most effective in maintaining seizure freedom.<\/jats:p>\n                  <jats:p>In summary, we demonstrate how the multidimensional spectrum of phenotypic features in STXBP1-related disorders can be assessed using a computational phenotype framework to facilitate the development of future precision-medicine approaches.<\/jats:p>","DOI":"10.1093\/brain\/awab327","type":"journal-article","created":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T23:11:39Z","timestamp":1631229099000},"page":"1668-1683","source":"Crossref","is-referenced-by-count":129,"title":["Assessing the landscape of\n                    <i>STXBP1<\/i>\n                    -related disorders in 534 individuals"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0205-0648","authenticated-orcid":false,"given":"Julie","family":"Xian","sequence":"first","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"Department of Biomedical and Health Informatics (DBHi), Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19146, USA"},{"name":"Neuroscience Program, University of Pennsylvania , Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shridhar","family":"Parthasarathy","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"Department of Biomedical and Health Informatics (DBHi), Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19146, USA"},{"name":"Department of Biology, The College of New Jersey , Ewing Township, NJ 08618, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0834-0750","authenticated-orcid":false,"given":"Sarah M","family":"Ruggiero","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia , Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0212-8318","authenticated-orcid":false,"given":"Ganna","family":"Balagura","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa , Genoa, Italy"},{"name":"Pediatric Neurology and Muscular Diseases Unit, IRCCS \u2018G. Gaslini\u2019 Institute , Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eryn","family":"Fitch","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia , Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8249-0549","authenticated-orcid":false,"given":"Katherine","family":"Helbig","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"Department of Biomedical and Health Informatics (DBHi), Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19146, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital, Sichuan University , Chengdu, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education , Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva","family":"Ganesan","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"Department of Biomedical and Health Informatics (DBHi), Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19146, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2718-296X","authenticated-orcid":false,"given":"Michael C","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"Department of Biomedical and Health Informatics (DBHi), Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19146, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin A","family":"Ellis","sequence":"additional","affiliation":[{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"Department of Biomedical and Health Informatics (DBHi), Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19146, USA"},{"name":"Department of Neurology, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1735-8178","authenticated-orcid":false,"given":"David","family":"Lewis-Smith","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University , Newcastle-upon-Tyne NE2 4HH, UK"},{"name":"Royal Victoria Infirmary , Newcastle-upon-Tyne NE1 4LP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Galer","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"Department of Biomedical and Health Informatics (DBHi), Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19146, USA"},{"name":"Center for Neuroengineering and Therapeutics, University of Pennsylvania , Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia , Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"Lewis Katz School of Medicine, Temple University , Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahgenn","family":"Cosico","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia , Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Baker","sequence":"additional","affiliation":[{"name":"MRC Cognition and Brain Sciences Unit, University of Cambridge , Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Darling","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department, Hospital Sant Joan de D\u00e9u, University of Barcelona , Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Veiga de Goes","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Pediatric Neurology Laboratory, Instituto Fernandes Figueira , Rio de Janeiro 22250-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle M","family":"El Achkar","sequence":"additional","affiliation":[{"name":"Division of Epilepsy and Clinical Neurophysiology and Epilepsy Genetics Program, Department of Neurology, Boston Children's Hospital , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Henje","family":"Doering","sequence":"additional","affiliation":[{"name":"Division of Pediatric Epileptology, Centre for Pediatric and Adolescent Medicine, University Hospital Heidelberg , 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Furia","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurophysiology, Danish Epilepsy Center Filadelfia , Dianalund 4293, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngeles","family":"Garc\u00eda-Cazorla","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department, Hospital Sant Joan de D\u00e9u, University of Barcelona , Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7138-6022","authenticated-orcid":false,"given":"Elena","family":"Gardella","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurophysiology, Danish Epilepsy Center Filadelfia , Dianalund 4293, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Geertjens","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Klein","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Neurology, Children's Hospital Colorado , Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kolesnik-Taylor","sequence":"additional","affiliation":[{"name":"MRC Cognition and Brain Sciences Unit, University of Cambridge , Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Lammertse","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam University Medical Center , de Boelelaan 1085, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeehun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, School of Medicine, Sungkyunkwan University , Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Mackie","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Neurology, Children's Hospital Colorado , Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mala","family":"Misra-Isrie","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam University Medical Center , de Boelelaan 1085, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5385-0119","authenticated-orcid":false,"given":"Heather","family":"Olson","sequence":"additional","affiliation":[{"name":"Division of Epilepsy and Clinical Neurophysiology and Epilepsy Genetics Program, Department of Neurology, Boston Children's Hospital , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Sexton","sequence":"additional","affiliation":[{"name":"Division of Epilepsy and Clinical Neurophysiology and Epilepsy Genetics Program, Department of Neurology, Boston Children's Hospital , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Sheidley","sequence":"additional","affiliation":[{"name":"Division of Epilepsy and Clinical Neurophysiology and Epilepsy Genetics Program, Department of Neurology, Boston Children's Hospital , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lacey","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Epilepsy and Clinical Neurophysiology and Epilepsy Genetics Program, Department of Neurology, Boston Children's Hospital , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza","family":"Sotero","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Pediatric Neurology Laboratory, Instituto Fernandes Figueira , Rio de Janeiro 22250-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Stamberger","sequence":"additional","affiliation":[{"name":"Division of Neurology, University Hospital Antwerp , Antwerp, Belgium"},{"name":"Applied & Translational Neurogenomics Group, VIB Center for Molecular Neurology, VIB , Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Syrbe","sequence":"additional","affiliation":[{"name":"Division of Pediatric Epileptology, Centre for Pediatric and Adolescent Medicine, University Hospital Heidelberg , 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim Marie","family":"Thalwitzer","sequence":"additional","affiliation":[{"name":"Division of Pediatric Epileptology, Centre for Pediatric and Adolescent Medicine, University Hospital Heidelberg , 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemiek","family":"van Berkel","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam , De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieke","family":"van Haelst","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam University Medical Center , de Boelelaan 1085, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Yuskaitis","sequence":"additional","affiliation":[{"name":"Division of Epilepsy and Clinical Neurophysiology and Epilepsy Genetics Program, Department of Neurology, Boston Children's Hospital , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2878-1147","authenticated-orcid":false,"given":"Sarah","family":"Weckhuysen","sequence":"additional","affiliation":[{"name":"Division of Neurology, University Hospital Antwerp , Antwerp, Belgium"},{"name":"Applied & Translational Neurogenomics Group, VIB Center for Molecular Neurology, VIB , Antwerp, Belgium"},{"name":"Translational Neurosciences, Faculty of Medicine and Health Science, University of Antwerp , Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Prosser","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlene","family":"Son Rigby","sequence":"additional","affiliation":[{"name":"STXBP1 Foundation , Apex, NC 27539, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Demarest","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Neurology, Children's Hospital Colorado , Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Pierce","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia , Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Beijing University First Hospital , Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke S","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurophysiology, Danish Epilepsy Center Filadelfia , Dianalund 4293, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilgo","family":"Bruining","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Amsterdam UMC, University of Amsterdam , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annapurna","family":"Poduri","sequence":"additional","affiliation":[{"name":"Division of Epilepsy and Clinical Neurophysiology and Epilepsy Genetics Program, Department of Neurology, Boston Children's Hospital , Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Zara","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa , Genoa, Italy"},{"name":"Unit of Medical Genetics, IRCCS Istituto Giannina Gaslini , Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5452-5000","authenticated-orcid":false,"given":"Matthijs","family":"Verhage","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Center for Neurogenomics and Cognitive Research (CNCR), Amsterdam University Medical Center , de Boelelaan 1085, 1081 HV Amsterdam, The Netherlands"},{"name":"Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam , De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Striano","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa , Genoa, Italy"},{"name":"Pediatric Neurology and Muscular Diseases Unit, IRCCS \u2018G. Gaslini\u2019 Institute , Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8486-0558","authenticated-orcid":false,"given":"Ingo","family":"Helbig","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia , Philadelphia, PA 19104, USA"},{"name":"Department of Biomedical and Health Informatics (DBHi), Children\u2019s Hospital of Philadelphia , Philadelphia, PA 19146, USA"},{"name":"Department of Neurology, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"issue":"4","key":"2022060319042227200_awab327-B1","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1093\/brain\/awaa051","article-title":"A catalogue of new incidence estimates of monogenic neurodevelopmental disorders caused by de novo variants","volume":"143","author":"Lopez-Rivera","year":"2020","journal-title":"Brain"},{"issue":"10","key":"2022060319042227200_awab327-B2","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1212\/WNL.0000000000002457","article-title":"STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy","volume":"86","author":"Stamberger","year":"2016","journal-title":"Neurology"},{"issue":"6","key":"2022060319042227200_awab327-B3","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/ng.150","article-title":"De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy","volume":"40","author":"Saitsu","year":"2008","journal-title":"Nat Genet"},{"issue":"1","key":"2022060319042227200_awab327-B4","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s11689-019-9278-9","article-title":"STXBP1-associated neurodevelopmental disorder: A comparative study of behavioural characteristics","volume":"11","author":"O'Brien","year":"2019","journal-title":"J Neurodev Disord"},{"issue":"5","key":"2022060319042227200_awab327-B5","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/mgg3.304","article-title":"Protein structure and phenotypic analysis of pathogenic and population missense variants in STXBP1","volume":"5","author":"Suri","year":"2017","journal-title":"Mol Genet Genomic Med"},{"issue":"3","key":"2022060319042227200_awab327-B6","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1038\/s41583-020-00418-4","article-title":"Sodium channelopathies in neurodevelopmental disorders","volume":"22","author":"Meisler","year":"2021","journal-title":"Nat Rev Neurosci"},{"key":"2022060319042227200_awab327-B7","doi-asserted-by":"crossref","first-page":"107970","DOI":"10.1016\/j.neuropharm.2020.107970","article-title":"Personalized medicine in genetic epilepsies\u2014Possibilities, challenges, and new frontiers","volume":"172","author":"Helbig","year":"2020","journal-title":"Neuropharmacology"},{"issue":"1","key":"2022060319042227200_awab327-B8","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.neuron.2020.05.036","article-title":"SNAREopathies: Diversity in mechanisms and symptoms","volume":"107","author":"Verhage","year":"2020","journal-title":"Neuron"},{"issue":"5913","key":"2022060319042227200_awab327-B9","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1126\/science.1161748","article-title":"Membrane fusion: Grappling with SNARE and SM proteins","volume":"323","author":"Sudhof","year":"2009","journal-title":"Science"},{"issue":"7419","key":"2022060319042227200_awab327-B10","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/nature11320","article-title":"Molecular machines governing exocytosis of synaptic vesicles","volume":"490","author":"Jahn","year":"2012","journal-title":"Nature"},{"issue":"5454","key":"2022060319042227200_awab327-B11","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1126\/science.287.5454.864","article-title":"Synaptic assembly of the brain in the absence of neurotransmitter secretion","volume":"287","author":"Verhage","year":"2000","journal-title":"Science"},{"issue":"2","key":"2022060319042227200_awab327-B12","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/jnc.15120","article-title":"STXBP1 encephalopathies: Clinical spectrum, disease mechanisms, and therapeutic strategies","volume":"157","author":"Abramov","year":"2021","journal-title":"J Neurochem"},{"issue":"3","key":"2022060319042227200_awab327-B13","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/jnc.15256","article-title":"Loss of MUNC18-1 leads to retrograde transport defects in neurons","volume":"157","author":"van Berkel","year":"2021","journal-title":"J Neurochem"},{"issue":"5","key":"2022060319042227200_awab327-B14","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1093\/brain\/awy046","article-title":"Protein instability, haploinsufficiency, and cortical hyper-excitability underlie STXBP1 encephalopathy","volume":"141","author":"Kovacevic","year":"2018","journal-title":"Brain"},{"issue":"1","key":"2022060319042227200_awab327-B15","doi-asserted-by":"crossref","first-page":"3986","DOI":"10.1038\/s41467-018-06507-4","article-title":"Mechanism-based rescue of Munc18-1 dysfunction in varied encephalopathies by chemical chaperones","volume":"9","author":"Guiberson","year":"2018","journal-title":"Nat Commun"},{"issue":"2","key":"2022060319042227200_awab327-B16","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1093\/brain\/awz391","article-title":"Homozygous STXBP1 variant causes encephalopathy and gain-of-function in synaptic transmission","volume":"143","author":"Lammertse","year":"2020","journal-title":"Brain"},{"issue":"4","key":"2022060319042227200_awab327-B17","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/s41436-020-01020-w","article-title":"De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy","volume":"23","author":"Klockner","year":"2021","journal-title":"Genet Med"},{"issue":"4","key":"2022060319042227200_awab327-B18","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.ajhg.2019.02.016","article-title":"Mutations in the neuronal vesicular SNARE VAMP2 affect synaptic membrane fusion and impair human neurodevelopment","volume":"104","author":"Salpietro","year":"2019","journal-title":"Am J Hum Genet"},{"issue":"12","key":"2022060319042227200_awab327-B19","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1038\/ng.3130","article-title":"Mutations in STX1B, encoding a presynaptic protein, cause fever-associated epilepsy syndromes","volume":"46","author":"Schubert","year":"2014","journal-title":"Nat Genet"},{"issue":"4","key":"2022060319042227200_awab327-B20","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1212\/WNL.0000000000004152","article-title":"DNM1 encephalopathy: A new disease of vesicle fission","volume":"89","author":"von Spiczak","year":"2017","journal-title":"Neurology"},{"issue":"6","key":"2022060319042227200_awab327-B21","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.ajhg.2019.04.001","article-title":"A recurrent missense variant in AP2M1 impairs clathrin-mediated endocytosis and causes developmental and epileptic encephalopathy","volume":"104","author":"Helbig","year":"2019","journal-title":"Am J Hum Genet"},{"issue":"13","key":"2022060319042227200_awab327-B22","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1212\/WNL.0b013e3181f4d7bf","article-title":"Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations","volume":"75","author":"Deprez","year":"2010","journal-title":"Neurology"},{"issue":"12","key":"2022060319042227200_awab327-B23","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1111\/j.1528-1167.2010.02767.x","article-title":"STXBP1 mutations cause not only Ohtahara syndrome but also West syndrome\u2014Result of Japanese cohort study","volume":"51","author":"Otsuka","year":"2010","journal-title":"Epilepsia"},{"issue":"10","key":"2022060319042227200_awab327-B24","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1111\/j.1528-1167.2011.03181.x","article-title":"Epileptic and nonepileptic features in patients with early onset epileptic encephalopathy and STXBP1 mutations","volume":"52","author":"Milh","year":"2011","journal-title":"Epilepsia"},{"issue":"14","key":"2022060319042227200_awab327-B25","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1212\/WNL.0000000000000291","article-title":"GABRA1 and STXBP1: Novel genetic causes of Dravet syndrome","volume":"82","author":"Carvill","year":"2014","journal-title":"Neurology"},{"issue":"3","key":"2022060319042227200_awab327-B26","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1136\/jmedgenet-2015-103568","article-title":"Identification of novel genetic causes of Rett syndrome-like phenotypes","volume":"53","author":"Lopes","year":"2016","journal-title":"J Med Genet"},{"key":"2022060319042227200_awab327-B27","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.yebeh.2018.12.018","article-title":"STXBP1 encephalopathy is associated with awake bruxism","volume":"92","author":"Rezazadeh","year":"2019","journal-title":"Epilepsy Behav"},{"issue":"15","key":"2022060319042227200_awab327-B28","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1056\/NEJMra1615014","article-title":"Classification, ontology, and precision medicine","volume":"379","author":"Haendel","year":"2018","journal-title":"N Engl J Med"},{"issue":"D1","key":"2022060319042227200_awab327-B29","doi-asserted-by":"crossref","first-page":"D1207","DOI":"10.1093\/nar\/gkaa1043","article-title":"The human phenotype ontology in 2021","volume":"49","author":"Kohler","year":"2021","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"2022060319042227200_awab327-B30","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.ajhg.2008.09.017","article-title":"The Human Phenotype Ontology: A tool for annotating and analyzing human hereditary disease","volume":"83","author":"Robinson","year":"2008","journal-title":"Am J Hum Genet"},{"issue":"4","key":"2022060319042227200_awab327-B31","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.ajhg.2020.08.003","article-title":"Semantic similarity analysis reveals robust gene\u2013disease relationships in developmental and epileptic encephalopathies","volume":"107","author":"Galer","year":"2020","journal-title":"Am J Hum Genet"},{"issue":"7","key":"2022060319042227200_awab327-B32","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1038\/s41436-021-01120-1","article-title":"Computational analysis of 10,860 phenotypic annotations in individuals with SCN2A-related disorders","volume":"23","author":"Crawford","year":"2021","journal-title":"Genet Med"},{"issue":"4","key":"2022060319042227200_awab327-B33","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.ajhg.2018.02.014","article-title":"Mutations in PMPCB encoding the catalytic subunit of the mitochondrial presequence protease cause neurodegeneration in early childhood","volume":"102","author":"Vogtle","year":"2018","journal-title":"Am J Hum Genet"},{"issue":"12","key":"2022060319042227200_awab327-B34","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1038\/s41436-020-0923-1","article-title":"A longitudinal footprint of genetic epilepsies using automated electronic medical record interpretation","volume":"22","author":"Ganesan","year":"2020","journal-title":"Genet Med"},{"key":"2022060319042227200_awab327-B35","author":"Epilepsy Foundation","year":"2021"},{"issue":"1","key":"2022060319042227200_awab327-B36","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/epi.16733","article-title":"Design and implementation of electronic health record common data elements for pediatric epilepsy: Foundations for a learning health care system","volume":"62","author":"Grinspan","year":"2021","journal-title":"Epilepsia"},{"issue":"11","key":"2022060319042227200_awab327-B37","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/S1474-4422(05)70199-X","article-title":"The United Kingdom Infantile Spasms Study (UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months: A multicentre randomised trial","volume":"4","author":"Lux","year":"2005","journal-title":"Lancet Neurol"},{"issue":"3","key":"2022060319042227200_awab327-B38","doi-asserted-by":"crossref","first-page":"193","DOI":"10.2310\/7010.2006.00044","article-title":"Efficacy of the ketogenic diet as a treatment option for epilepsy: Eta-analysis","volume":"21","author":"Henderson","year":"2006","journal-title":"J Child Neurol"},{"key":"2022060319042227200_awab327-B39","author":"R Core Team","year":"2017"},{"issue":"1","key":"2022060319042227200_awab327-B40","doi-asserted-by":"crossref","first-page":"e12354","DOI":"10.15252\/emmm.202012354","article-title":"Targeted stabilization of Munc18-1 function via pharmacological chaperones","volume":"13","author":"Abramov","year":"2021","journal-title":"EMBO Mol Med"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awab327\/42574927\/awab327.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awab327\/43948400\/awab327.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awab327\/43948400\/awab327.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T15:05:26Z","timestamp":1654268726000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/145\/5\/1668\/6433675"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,23]]},"references-count":40,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,11,23]]},"published-print":{"date-parts":[[2022,6,3]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awab327","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,5,1]]},"published":{"date-parts":[[2021,11,23]]}}}