{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:47:12Z","timestamp":1791978432170,"version":"4.4.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T00:00:00Z","timestamp":1633305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"U.S. National Human Genome Research Institute (NHGRI) and National Heart Lung and Blood Institute (NHBLI) to the Baylor-Hopkins Center for Mendelian Genomics","award":["UM1 HG006542, J.R.L"],"award-info":[{"award-number":["UM1 HG006542, J.R.L"]}]},{"name":"Baylor College of Medicine Human Genome Sequencing Center","award":["U54HG003273 to R.A.G."],"award-info":[{"award-number":["U54HG003273 to R.A.G."]}]},{"name":"U.S. National Institute of Neurological Disorders and Stroke","award":["R35NS105078 to J.R.L."],"award-info":[{"award-number":["R35NS105078 to J.R.L."]}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"crossref","award":["512848 to J.R.L."],"award-info":[{"award-number":["512848 to J.R.L."]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008982","name":"Qatar National Research Fund","doi-asserted-by":"crossref","award":["NPRP11S-0110\u2013180250 to K.F."],"award-info":[{"award-number":["NPRP11S-0110\u2013180250 to K.F."]}],"id":[{"id":"10.13039\/100008982","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"The Wellcome Trust","doi-asserted-by":"publisher","award":["WT093205 MA and WT104033AIA"],"award-info":[{"award-number":["WT093205 MA and WT104033AIA"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute for Health Research University College London Hospitals Biomedical Research Centre","award":["MR\/S01165X\/1, MR\/S005021\/1, G0601943"],"award-info":[{"award-number":["MR\/S01165X\/1, MR\/S005021\/1, G0601943"]}]},{"name":"Rosetree Trust, Ataxia UK, MSA Trust, Brain Research UK, Sparks GOSH Charity, Muscular Dystrophy UK (MDUK), and Muscular Dystrophy Association"},{"name":"Medical Genetics Research Fellowship Program through the United States National Institute of Health","award":["T32 GM007526-42"],"award-info":[{"award-number":["T32 GM007526-42"]}]},{"name":"National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Programme and a Wellcome Trust Core Award","award":["203141\/Z\/16\/Z"],"award-info":[{"award-number":["203141\/Z\/16\/Z"]}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001819","name":"International Rett Syndrome Foundation","doi-asserted-by":"crossref","award":["#3701\u20131."],"award-info":[{"award-number":["#3701\u20131."]}],"id":[{"id":"10.13039\/100001819","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000051","name":"NHGRI","doi-asserted-by":"publisher","award":["K08 HG008986"],"award-info":[{"award-number":["K08 HG008986"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Isabelle Rapin Scholar Recipient for clinical research in autoimmune encephalitis"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The solute carrier (SLC) superfamily encompasses &amp;gt;400 transmembrane transporters involved in the exchange of amino acids, nutrients, ions, metals, neurotransmitters and metabolites across biological membranes. SLCs are highly expressed in the mammalian brain; defects in nearly 100 unique SLC-encoding genes (OMIM: https:\/\/www.omim.org) are associated with rare Mendelian disorders including developmental and epileptic encephalopathy and severe neurodevelopmental disorders.<\/jats:p>\n               <jats:p>Exome sequencing and family-based rare variant analyses on a cohort with neurodevelopmental disorders identified two siblings with developmental and epileptic encephalopathy and a shared deleterious homozygous splicing variant in SLC38A3. The gene encodes SNAT3, a sodium-coupled neutral amino acid transporter and a principal transporter of the amino acids asparagine, histidine, and glutamine, the latter being the precursor for the neurotransmitters GABA and glutamate. Additional subjects with a similar developmental and epileptic encephalopathy phenotype and biallelic predicted-damaging SLC38A3 variants were ascertained through GeneMatcher and collaborations with research and clinical molecular diagnostic laboratories. Untargeted metabolomic analysis was performed to identify novel metabolic biomarkers.<\/jats:p>\n               <jats:p>Ten individuals from seven unrelated families from six different countries with deleterious biallelic variants in SLC38A3 were identified. Global developmental delay, intellectual disability, hypotonia, and absent speech were common features while microcephaly, epilepsy, and visual impairment were present in the majority. Epilepsy was drug-resistant in half. Metabolomic analysis revealed perturbations of glutamate, histidine, and nitrogen metabolism in plasma, urine, and CSF of selected subjects, potentially representing biomarkers of disease.<\/jats:p>\n               <jats:p>Our data support the contention that SLC38A3 is a novel disease gene for developmental and epileptic encephalopathy and illuminate the likely pathophysiology of the disease as perturbations in glutamine homeostasis.<\/jats:p>","DOI":"10.1093\/brain\/awab369","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T20:31:38Z","timestamp":1633033898000},"page":"909-924","source":"Crossref","is-referenced-by-count":28,"title":["Biallelic variants in <i>SLC38A3<\/i> encoding a glutamine transporter cause epileptic encephalopathy"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2233-3423","authenticated-orcid":false,"given":"Dana","family":"Marafi","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Department of Pediatrics, Faculty of Medicine, Kuwait University, P.O. Box 24923, 13110 Safat, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawid M","family":"Fatih","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-4010","authenticated-orcid":false,"given":"Rauan","family":"Kaiyrzhanov","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disorders Institute of Neurology, University College London, Queen Square, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5508-4673","authenticated-orcid":false,"given":"Matteo P","family":"Ferla","sequence":"additional","affiliation":[{"name":"NIHR Oxford Biomedical Research Centre, Oxford OX4 2PG, UK"},{"name":"Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charul","family":"Gijavanekar","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Baylor Genetics Laboratory, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aljazi","family":"Al-Maraghi","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Sidra Medicine, Doha 26999, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Baylor Genetics Laboratory, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Sites","sequence":"additional","affiliation":[{"name":"Division of Molecular and Human Genetics, Nationwide Children's Hospital, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hessa S","family":"Alsaif","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Al-Owain","sequence":"additional","affiliation":[{"name":"Department of Medical Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"},{"name":"Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University 11533, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Zakkariah","sequence":"additional","affiliation":[{"name":"Section of Child Neurology, Department of Pediatrics, Al-adan Hospital, Riqqa, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehab","family":"El-Anany","sequence":"additional","affiliation":[{"name":"Section of Child Neurology, Department of Pediatrics, Al-adan Hospital, Riqqa, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulviyya","family":"Guliyeva","sequence":"additional","affiliation":[{"name":"MediClub Hospital, Baku, AZ 1010 Azerbaijan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sughra","family":"Guliyeva","sequence":"additional","affiliation":[{"name":"MediClub Hospital, Baku, AZ 1010 Azerbaijan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colette","family":"Gaba","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Bon Secours Mercy Health, Toledo, OH 43608, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ateeq","family":"Haseeb","sequence":"additional","affiliation":[{"name":"Mercy Children\u2019s Hospital, Toledo, OH 43608, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal M","family":"Alhashem","sequence":"additional","affiliation":[{"name":"Division of Medical Genetic and Metabolic Medicine, Department of Pediatrics, Prince Sultan Medical Military City, Riyadh, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enam","family":"Danish","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliki","family":"Karageorgou","sequence":"additional","affiliation":[{"name":"Centogene GmbH, Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Beetz","sequence":"additional","affiliation":[{"name":"Centogene GmbH, Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa A","family":"Subhi","sequence":"additional","affiliation":[{"name":"Neurosciences Department, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sureni V","family":"Mullegama","sequence":"additional","affiliation":[{"name":"GeneDx, Gaithersburg, MD 20877, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Torti","sequence":"additional","affiliation":[{"name":"GeneDx, Gaithersburg, MD 20877, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monisha","family":"Sebastin","sequence":"additional","affiliation":[{"name":"Albert Einstein College of Medicine and the Children's Hospital at Montefiore, Bronx, New York 10467, USA"},{"name":"Division of Genetics, Department of Pediatrics, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York, 10467, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margo Sheck","family":"Breilyn","sequence":"additional","affiliation":[{"name":"Albert Einstein College of Medicine and the Children's Hospital at Montefiore, Bronx, New York 10467, USA"},{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Duberstein","sequence":"additional","affiliation":[{"name":"Isabelle Rapin Division of Child Neurology in the Saul R Korey Department of Neurology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed S","family":"Abdel-Hamid","sequence":"additional","affiliation":[{"name":"Department of Medical Molecular Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadahiro","family":"Mitani","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haowei","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5664-7987","authenticated-orcid":false,"given":"Jill A","family":"Rosenfeld","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Baylor Genetics Laboratory, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini N","family":"Jhangiani","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep","family":"Coban Akdemir","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny C","family":"Taylor","sequence":"additional","affiliation":[{"name":"NIHR Oxford Biomedical Research Centre, Oxford OX4 2PG, UK"},{"name":"Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid A","family":"Fakhro","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Sidra Medicine, Doha 26999, Qatar"},{"name":"Department of Genetic Medicine, Weill Cornell Medical College, Doha, Qatar"},{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University, Doha 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill V","family":"Hunter","sequence":"additional","affiliation":[{"name":"E.B. Singleton Department of Pediatric Radiology, Texas Children\u2019s Hospital, Houston, TX 77030, USA"},{"name":"Department of Radiology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davut","family":"Pehlivan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Texas Children's Hospital, Houston, TX 77030, USA"},{"name":"Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha S","family":"Zaki","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph G","family":"Gleeson","sequence":"additional","affiliation":[{"name":"Rady Children's Institute for Genomic Medicine, Howard Hughes Medical Institute, University of California, San Diego, CA 92123, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Maroofian","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disorders Institute of Neurology, University College London, Queen Square, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2866-7777","authenticated-orcid":false,"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disorders Institute of Neurology, University College London, Queen Square, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4814-6765","authenticated-orcid":false,"given":"Jennifer E","family":"Posey","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V Reid","family":"Sutton","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Baylor Genetics Laboratory, Houston, TX 77030, USA"},{"name":"Texas Children's Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4158-341X","authenticated-orcid":false,"given":"Fowzan S","family":"Alkuraya","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics, Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah H","family":"Elsea","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Baylor Genetics Laboratory, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R","family":"Lupski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA"},{"name":"Texas Children's Hospital, Houston, TX 77030, USA"},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,4]]},"reference":[{"issue":"7","key":"2022042902223588100_awab369-B1","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.cell.2011.05.025","article-title":"Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy","volume":"145","author":"Klassen","year":"2011","journal-title":"Cell."},{"issue":"3","key":"2022042902223588100_awab369-B2","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/S1474-4422(15)00250-1","article-title":"The genetic landscape of the epileptic encephalopathies of infancy and childhood","volume":"15","author":"McTague","year":"2016","journal-title":"Lancet Neurol."},{"issue":"2","key":"2022042902223588100_awab369-B3","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ajps.2019.09.002","article-title":"The solute carrier transporters and the brain: Physiological and pharmacological implications","volume":"15","author":"Hu","year":"2020","journal-title":"Asian J Pharm Sci."},{"issue":"1","key":"2022042902223588100_awab369-B4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jmcb\/mjy052","article-title":"The SLC transporter in nutrient and metabolic sensing, regulation, and drug development","volume":"11","author":"Zhang","year":"2019","journal-title":"J Mol Cell Biol."},{"issue":"Database issue","key":"2022042902223588100_awab369-B5","doi-asserted-by":"crossref","first-page":"D789","DOI":"10.1093\/nar\/gku1205","article-title":"OMIM.org: Online Mendelian Inheritance in Man (OMIM\u00ae), an online catalog of human genes and genetic disorders","volume":"43","author":"Amberger","year":"2015","journal-title":"Nucleic Acids Res."},{"issue":"2","key":"2022042902223588100_awab369-B6","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.ajhg.2017.07.004","article-title":"De Novo mutations in YWHAG cause early-onset epilepsy","volume":"101","author":"Guella","year":"2017","journal-title":"Am J Hum Genet."},{"key":"2022042902223588100_awab369-B7","doi-asserted-by":"crossref","first-page":"988","DOI":"10.3389\/fneur.2019.00988","article-title":"Diagnostic yield of epilepsy panel testing in patients with seizure onset within the first year of life","volume":"10","author":"Jang","year":"2019","journal-title":"Front Neurol."},{"issue":"12","key":"2022042902223588100_awab369-B8","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1586\/14737159.2015.1113132","article-title":"The contribution of next generation sequencing to epilepsy genetics","volume":"15","author":"M\u00f8ller","year":"2015","journal-title":"Expert Rev Mol Diagn."},{"issue":"3","key":"2022042902223588100_awab369-B9","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.ymgme.2018.08.005","article-title":"Identification of a pathogenic PMP2 variant in a multi-generational family with CMT type 1: Clinical gene panels versus genome-wide approaches to molecular diagnosis","volume":"125","author":"Punetha","year":"2018","journal-title":"Mol Genet Metab."},{"issue":"13","key":"2022042902223588100_awab369-B10","doi-asserted-by":"crossref","first-page":"e1770","DOI":"10.1212\/WNL.0000000000011655","article-title":"Diagnostic yield of whole genome sequencing after nondiagnostic exome sequencing or gene panel in developmental and epileptic encephalopathies","volume":"96","author":"Palmer","year":"2021","journal-title":"Neurology."},{"issue":"11","key":"2022042902223588100_awab369-B11","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1002\/humu.23609","article-title":"Quantifying the potential of functional evidence to reclassify variants of uncertain significance in the categorical and Bayesian interpretation frameworks","volume":"39","author":"Brnich","year":"2018","journal-title":"Hum Mutat."},{"issue":"6","key":"2022042902223588100_awab369-B12","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1080\/19336950.2016.1207024","article-title":"Regulation and function of the SLC38A3\/SNAT3 glutamine transporter","volume":"10","author":"Rubio-Aliaga","year":"2016","journal-title":"Channels (Austin)."},{"issue":"3","key":"2022042902223588100_awab369-B13","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.neuron.2015.09.048","article-title":"Genes that affect brain structure and function identified by rare variant analyses of Mendelian neurologic disease","volume":"88","author":"Karaca","year":"2015","journal-title":"Neuron."},{"issue":"7809","key":"2022042902223588100_awab369-B14","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature."},{"issue":"10","key":"2022042902223588100_awab369-B15","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/humu.22844","article-title":"GeneMatcher: A matching tool for connecting investigators with an interest in the same gene","volume":"36","author":"Sobreira","year":"2015","journal-title":"Hum Mutat."},{"issue":"6","key":"2022042902223588100_awab369-B16","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/j.ajhg.2019.04.011","article-title":"Lessons learned from large-scale, first-tier clinical exome sequencing in a highly consanguineous population","volume":"104","author":"Monies","year":"2019","journal-title":"Am J Hum Genet."},{"issue":"12","key":"2022042902223588100_awab369-B17","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1038\/gim.2018.33","article-title":"Phenotypic expansion illuminates multilocus pathogenic variation","volume":"20","author":"Karaca","year":"2018","journal-title":"Genet Med."},{"issue":"2","key":"2022042902223588100_awab369-B18","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/gim.2012.169","article-title":"American College of Medical Genetics and Genomics: Standards and guidelines for documenting suspected consanguinity as an incidental finding of genomic testing","volume":"15","author":"Rehder","year":"2013","journal-title":"Genet Med."},{"issue":"7","key":"2022042902223588100_awab369-B19","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1002\/ajmg.a.62192","article-title":"A novel homozygous SLC13A5 whole-gene deletion generated by Alu\/Alu-mediated rearrangement in an Iraqi family with epileptic encephalopathy","volume":"185","author":"Duan","year":"2021","journal-title":"Am J Med Genet A."},{"issue":"6","key":"2022042902223588100_awab369-B20","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nprot.2015.053","article-title":"The Phyre2 web portal for protein modeling, prediction and analysis","volume":"10","author":"Kelley","year":"2015","journal-title":"Nat Protoc."},{"key":"2022042902223588100_awab369-B21","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1471-2105-9-40","article-title":"I-TASSER server for protein 3D structure prediction","volume":"9","author":"Zhang","year":"2008","journal-title":"BMC Bioinformatics."},{"issue":"5","key":"2022042902223588100_awab369-B22","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1093\/bioinformatics\/btq007","article-title":"PyRosetta: A script-based interface for implementing molecular modeling algorithms using Rosetta","volume":"26","author":"Chaudhury","year":"2010","journal-title":"Bioinformatics."},{"issue":"1","key":"2022042902223588100_awab369-B23","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/pro.2389","article-title":"Relaxation of backbone bond geometry improves protein energy landscape modeling","volume":"23","author":"Conway","year":"2014","journal-title":"Protein Sci."},{"issue":"6","key":"2022042902223588100_awab369-B24","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/s41594-018-0072-2","article-title":"Crystal structure of arginine-bound lysosomal transporter SLC38A9 in the cytosol-open state","volume":"25","author":"Lei","year":"2018","journal-title":"Nat Struct Mol Biol."},{"issue":"Pt 17","key":"2022042902223588100_awab369-B25","doi-asserted-by":"crossref","first-page":"3179","DOI":"10.1113\/jphysiol.2010.192153","article-title":"Phosphoinositides: Lipid regulators of membrane proteins","volume":"588","author":"Falkenburger","year":"2010","journal-title":"J Physiol."},{"issue":"7714","key":"2022042902223588100_awab369-B26","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/s41586-018-0325-6","article-title":"PtdIns(4,5)P2 stabilizes active states of GPCRs and enhances selectivity of G-protein coupling","volume":"559","author":"Yen","year":"2018","journal-title":"Nature."},{"issue":"5","key":"2022042902223588100_awab369-B27","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1093\/bioinformatics\/btk023","article-title":"OPM: Orientations of Proteins in Membranes database","volume":"22","author":"Lomize","year":"2006","journal-title":"Bioinformatics."},{"issue":"8","key":"2022042902223588100_awab369-B28","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1016\/j.bpj.2020.03.006","article-title":"Protein Structure Prediction and Design in a Biologically Realistic Implicit Membrane","volume":"118","author":"Alford","year":"2020","journal-title":"Biophys J."},{"issue":"10","key":"2022042902223588100_awab369-B29","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.1093\/bioinformatics\/btaa104","article-title":"MichelaNglo: Sculpting protein views on web pages without coding","volume":"36","author":"Ferla","year":"2020","journal-title":"Bioinformatics."},{"issue":"2","key":"2022042902223588100_awab369-B30","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ymgme.2017.04.005","article-title":"Elucidation of the complex metabolic profile of cerebrospinal fluid using an untargeted biochemical profiling assay","volume":"121","author":"Kennedy","year":"2017","journal-title":"Mol Genet Metab."},{"issue":"6","key":"2022042902223588100_awab369-B31","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1007\/s10545-015-9843-7","article-title":"Untargeted metabolomic analysis for the clinical screening of inborn errors of metabolism","volume":"38","author":"Miller","year":"2015","journal-title":"J Inherit Metab Dis."},{"issue":"2","key":"2022042902223588100_awab369-B32","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1093\/jalm\/jfz026","article-title":"Precision of a Clinical Metabolomics Profiling Platform for Use in the Identification of Inborn Errors of Metabolism","volume":"5","author":"Ford","year":"2020","journal-title":"J Appl Lab Med."},{"issue":"9","key":"2022042902223588100_awab369-B33","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1038\/s41436-020-0827-0","article-title":"Integrated analysis of metabolomic profiling and exome data supplements sequence variant interpretation, classification, and diagnosis","volume":"22","author":"Alaimo","year":"2020","journal-title":"Genet Med."},{"issue":"8","key":"2022042902223588100_awab369-B34","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1111\/bdi.12982","article-title":"Cerebrospinal fluid metabolomics uniquely identifies pathways suggesting risk for anesthesia reactions during electroconvulsive therapy for bipolar disorder","volume":"22","author":"Berner","year":"2020","journal-title":"Bipolar Disord."},{"issue":"9","key":"2022042902223588100_awab369-B35","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1089\/gtmb.2015.0291","article-title":"Metabolomic profiling of human urine as a screen for multiple inborn errors of metabolism","volume":"20","author":"Kennedy","year":"2016","journal-title":"Genet Test Mol Biomarkers."},{"issue":"2","key":"2022042902223588100_awab369-B36","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s00424-015-1742-0","article-title":"Loss of function mutation of the Slc38a3 glutamine transporter reveals its critical role for amino acid metabolism in the liver, brain, and kidney","volume":"468","author":"Chan","year":"2016","journal-title":"Pflugers Arch."},{"issue":"8","key":"2022042902223588100_awab369-B37","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1111\/dmcn.14152","article-title":"Gene mutations in paediatric epilepsies cause NMDA-pathy, and phasic and tonic GABA-pathy","volume":"61","author":"Gataullina","year":"2019","journal-title":"Dev Med Child Neurol."},{"issue":"8","key":"2022042902223588100_awab369-B38","doi-asserted-by":"crossref","first-page":"a022863","DOI":"10.1101\/cshperspect.a022863","article-title":"Glutamatergic mechanisms associated with seizures and epilepsy","volume":"5","author":"Barker-Haliski","year":"2015","journal-title":"Cold Spring Harb Perspect Med."},{"issue":"5","key":"2022042902223588100_awab369-B39","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1093\/brain\/awaa085","article-title":"Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy","volume":"143","author":"Chatron","year":"2020","journal-title":"Brain."},{"issue":"8","key":"2022042902223588100_awab369-B40","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.1093\/brain\/awaa178","article-title":"Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants","volume":"143","author":"Neuray","year":"2020","journal-title":"Brain."},{"issue":"3","key":"2022042902223588100_awab369-B41","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1001\/jamaneurol.2018.2941","article-title":"Identification of a loss-of-function mutation in the context of glutaminase deficiency and neonatal epileptic encephalopathy","volume":"76","author":"Rumping","year":"2019","journal-title":"JAMA Neurol."},{"issue":"1","key":"2022042902223588100_awab369-B42","doi-asserted-by":"crossref","first-page":"5629","DOI":"10.1038\/s41598-018-24000-2","article-title":"NRF2 regulates the glutamine transporter Slc38a3 (SNAT3) in kidney in response to metabolic acidosis","volume":"8","author":"Lister","year":"2018","journal-title":"Sci Rep."},{"issue":"11","key":"2022042902223588100_awab369-B43","doi-asserted-by":"crossref","first-page":"5151","DOI":"10.1167\/iovs.08-2245","article-title":"Expression and function of system N glutamine transporters (SN1\/SN2 or SNAT3\/SNAT5) in retinal ganglion cells","volume":"49","author":"Umapathy","year":"2008","journal-title":"Invest Ophthalmol Vis Sci."},{"issue":"4","key":"2022042902223588100_awab369-B44","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1097\/WNO.0000000000000609","article-title":"Vigabatrin: Lessons learned from the United States experience","volume":"38","author":"Foroozan","year":"2018","journal-title":"J Neuroophthalmol."},{"issue":"1","key":"2022042902223588100_awab369-B45","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12987-020-0178-x","article-title":"Choroid plexus LAT2 and SNAT3 as partners in CSF amino acid homeostasis maintenance","volume":"17","author":"Dolgodilina","year":"2020","journal-title":"Fluids Barriers CNS."},{"issue":"9","key":"2022042902223588100_awab369-B46","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1038\/s12276-020-00504-8","article-title":"Glutamine reliance in cell metabolism","volume":"52","author":"Yoo","year":"2020","journal-title":"Exp Mol Med."},{"issue":"1","key":"2022042902223588100_awab369-B47","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1152\/physrev.00062.2017","article-title":"Brain glucose metabolism: Integration of energetics with function","volume":"99","author":"Dienel","year":"2019","journal-title":"Physiol Rev."},{"issue":"10","key":"2022042902223588100_awab369-B48","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1038\/gim.2017.262","article-title":"A metabolomic map of Zellweger spectrum disorders reveals novel disease biomarkers","volume":"20","author":"Wangler","year":"2018","journal-title":"Genet Med."},{"issue":"647","key":"2022042902223588100_awab369-B49","doi-asserted-by":"crossref","first-page":"647","DOI":"10.3389\/fpsyt.2019.00647","article-title":"Untargeted metabolomics for autism spectrum disorders: Current status and future directions","volume":"10","author":"Glinton","year":"2019","journal-title":"Front Psychiatry."},{"issue":"9","key":"2022042902223588100_awab369-B50","doi-asserted-by":"crossref","first-page":"e0184022","DOI":"10.1371\/journal.pone.0184022","article-title":"Biochemical phenotyping unravels novel metabolic abnormalities and potential biomarkers associated with treatment of GLUT1 deficiency with ketogenic diet","volume":"12","author":"Cappuccio","year":"2017","journal-title":"PLoS One."},{"issue":"4","key":"2022042902223588100_awab369-B51","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.ymgme.2017.06.009","article-title":"Analyses of SLC13A5-epilepsy patients reveal perturbations of TCA cycle","volume":"121","author":"Bainbridge","year":"2017","journal-title":"Mol Genet Metab."},{"issue":"1","key":"2022042902223588100_awab369-B52","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0378-4347(94)80064-2","article-title":"Liquid chromatographic-mass spectrometric analysis of N-acetylamino acids in human urine","volume":"657","author":"Sugahara","year":"1994","journal-title":"J Chromatogr B Biomed Appl."},{"issue":"12","key":"2022042902223588100_awab369-B53","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1002\/nbm.3045","article-title":"Glutamate and glutamine: A review of in vivo MRS in the human brain","volume":"26","author":"Ramadan","year":"2013","journal-title":"NMR Biomed."},{"issue":"4","key":"2022042902223588100_awab369-B54","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.biopsych.2006.07.022","article-title":"Evidence for cortical dysfunction in autism: A proton magnetic resonance spectroscopic imaging study","volume":"61","author":"DeVito","year":"2007","journal-title":"Biol Psychiatry."},{"key":"2022042902223588100_awab369-B55","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1528-1167.2008.01508.x","article-title":"Neurometabolism in human epilepsy","volume":"49 (Suppl 3(0 3)","author":"Pan","year":"2008","journal-title":"Epilepsia."},{"key":"2022042902223588100_awab369-B56","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/j.1600-0404.2011.01596.x","article-title":"Mechanism of action of vigabatrin: Correcting misperceptions","volume":"124","author":"Ben-Menachem","year":"2011","journal-title":"Acta Neurol Scand Suppl."},{"issue":"4","key":"2022042902223588100_awab369-B57","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s11940-016-0401-x","article-title":"The role of benzodiazepines in the treatment of epilepsy","volume":"18","author":"Ochoa","year":"2016","journal-title":"Curr Treat Options Neurol."},{"key":"2022042902223588100_awab369-B58","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3389\/fnins.2019.00394","article-title":"2-Pyrrolidinone and succinimide as clinical screening biomarkers for GABA-transaminase deficiency: Anti-seizure medications impact accurate diagnosis","volume":"13","author":"Kennedy","year":"2019","journal-title":"Front Neurosci."}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awab369\/42901793\/awab369.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/145\/3\/909\/43499938\/awab369.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/145\/3\/909\/43499938\/awab369.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T02:36:54Z","timestamp":1651199814000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/145\/3\/909\/6380942"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,4]]},"references-count":58,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,10,4]]},"published-print":{"date-parts":[[2022,4,29]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awab369","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,3,1]]},"published":{"date-parts":[[2021,10,4]]}}}