{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:35:23Z","timestamp":1790742923592,"version":"4.1.0"},"reference-count":7,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T00:00:00Z","timestamp":1609718400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T00:00:00Z","timestamp":1609718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pediatr"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>N-methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the central nervous system. The functional NMDA receptors are heterotetramers consisting mainly of two GluN1 and two GluN2 subunits. GluN2 is encoded by the <jats:italic>GRIN2D<\/jats:italic> gene. A few case series have shown that <jats:italic>GRIN2D<\/jats:italic> variants are linked to developmental and epileptic encephalopathy. In this article, we report a novel <jats:italic>GRIN2D<\/jats:italic> variant, namely c.2021C\u2009&gt;\u2009A (p.T674K) in a neonate with intractable epileptic encephalopathy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>A 12-day-old boy who had stiffness of the lower and upper extremities since birth was transferred from a local hospital to our department. On admission, the patient presented with head tilting backwards, staring, apnea and hypertonia of limbs. Video electroencephalogram showed continuous, generalized or multi-focal spike-wave and spike-and-slow wave discharges and hypsarrhythmia. A treatment regimen composed of phenobarbital, midazolam, levetiracetam and clonazepam was administered, which however led to only partial control of the seizure. Whole-exome sequencing identified c.2021C\u2009&gt;\u2009A (p.T674K) in <jats:italic>GRIN2D<\/jats:italic> in the patient while such a mutation was not detected in the parents. The patient was hospitalized for 1 month and died of sudden cardio-respiratory arrest 2 weeks after discharge.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>A novel variant of <jats:italic>GRIN2D<\/jats:italic> was identified in a neonate with epileptic encephalopathy. Epilepsy associated with this <jats:italic>GRIN2D<\/jats:italic> mutation is refractory to conventional anti-epileptic medications.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12887-020-02462-6","type":"journal-article","created":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T10:03:57Z","timestamp":1609754637000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Identification of a novel GRIN2D variant in a neonate with intractable epileptic encephalopathy-a case report"],"prefix":"10.1186","volume":"21","author":[{"given":"Jiancheng","family":"Jiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junchen","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingzhi","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,4]]},"reference":[{"key":"2462_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-1-4939-7321-7_1","volume":"1677","author":"KB Hansen","year":"2017","unstructured":"Hansen KB, Yi F, Perszyk RE, Menniti FS, Traynelis SF. NMDA receptors in the central nervous system. Methods Mol Biol. 2017;1677:1\u201380.","journal-title":"Methods Mol Biol"},{"issue":"6","key":"2462_CR2","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/nrn3504","volume":"14","author":"P Paoletti","year":"2013","unstructured":"Paoletti P, Bellone C, Zhou Q. NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease. Nat Rev Neurosci. 2013;14(6):383\u2013400.","journal-title":"Nat Rev Neurosci"},{"issue":"6187","key":"2462_CR3","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1126\/science.1251915","volume":"344","author":"E Karakas","year":"2014","unstructured":"Karakas E, Furukawa H. Crystal structure of a heterotetrameric NMDA receptor ion channel. Science. 2014;344(6187):992\u20137.","journal-title":"Science"},{"issue":"10","key":"2462_CR4","doi-asserted-by":"publisher","first-page":"3009","DOI":"10.1093\/brain\/awz232","volume":"142","author":"W XiangWei","year":"2019","unstructured":"XiangWei W, Kannan V, Xu Y, et al. Heterogeneous clinical and functional features of GRIN2D-related developmental and epileptic encephalopathy. Brain. 2019;142(10):3009\u201327.","journal-title":"Brain"},{"issue":"6","key":"2462_CR5","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1111\/cge.13454","volume":"94","author":"N Tsuchida","year":"2018","unstructured":"Tsuchida N, Hamada K, Shiina M, et al. GRIN2D variants in three cases of developmental and epileptic encephalopathy. Clin Genet. 2018;94(6):538\u201347.","journal-title":"Clin Genet"},{"issue":"4","key":"2462_CR6","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.ajhg.2016.07.013","volume":"99","author":"D Li","year":"2016","unstructured":"Li D, Yuan H, Ortiz-Gonzalez XR, et al. GRIN2D recurrent de novo dominant mutation causes a severe epileptic encephalopathy treatable with NMDA receptor channel blockers. Am J Hum Genet. 2016;99(4):802\u201316.","journal-title":"Am J Hum Genet"},{"issue":"5","key":"2462_CR7","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405\u201324.","journal-title":"Genet Med"}],"container-title":["BMC Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12887-020-02462-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12887-020-02462-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12887-020-02462-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T10:06:37Z","timestamp":1609754797000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcpediatr.biomedcentral.com\/articles\/10.1186\/s12887-020-02462-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,4]]},"references-count":7,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2462"],"URL":"https:\/\/doi.org\/10.1186\/s12887-020-02462-6","relation":{},"ISSN":["1471-2431"],"issn-type":[{"value":"1471-2431","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,4]]},"assertion":[{"value":"12 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"As this is a case report, ethics approval is not reruired as per our institution\u2019s policy. Informed consent was obtained from the parents of the patient.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written, informed consent was obtained from the parents of the patient for publication of this case report.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"5"}}