{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:15:44Z","timestamp":1787026544347,"version":"build-2736575974"},"reference-count":10,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pathogenic variants in glutamate receptor, ionotropic, NMDA\u20101 (<jats:italic>GRIN1<\/jats:italic>) cause an autosomal dominant or recessive neurodevelopmental disorder with global developmental delay, with or without seizures (AD or AR <jats:italic>GRIN1<\/jats:italic>\u2010NDD). Here, we describe a novel homozygous canonical splice site variant in <jats:italic>GRIN1<\/jats:italic> in a 12\u2010month\u2010old boy with early infantile epileptic encephalopathy and severe global developmental delay. This represents only the second family with a homozygous predicted\u2010null variant in <jats:italic>GRIN1<\/jats:italic> reported to date. We review the published literature on AR <jats:italic>GRIN1\u2010<\/jats:italic>NDD and find that the phenotype in our patient is much more severe than those seen with homozygous missense variants. A similarly severe phenotype of intractable epilepsy and infantile death has only been reported in one other family with a homozygous nonsense variant in <jats:italic>GRIN1<\/jats:italic>. We, therefore, propose that biallelic predicted\u2010null variants in <jats:italic>GRIN1<\/jats:italic> can cause a markedly more severe clinical phenotype than AR <jats:italic>GRIN1<\/jats:italic>\u2010NDD caused by missense variants.<\/jats:p>","DOI":"10.1002\/ajmg.a.62528","type":"journal-article","created":{"date-parts":[[2021,10,8]],"date-time":"2021-10-08T01:28:01Z","timestamp":1633656481000},"page":"595-599","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A homozygous <scp><i>GRIN1<\/i><\/scp> null variant causes a more severe phenotype of early infantile epileptic encephalopathy"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0260-7020","authenticated-orcid":false,"given":"Alexander J. M.","family":"Blakes","sequence":"first","affiliation":[{"name":"Manchester Centre for Genomic Medicine, Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"},{"name":"Royal Manchester Children's Hospital  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4887-1003","authenticated-orcid":false,"given":"Joel","family":"English","sequence":"additional","affiliation":[{"name":"Royal Manchester Children's Hospital  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8527-2210","authenticated-orcid":false,"given":"Siddharth","family":"Banka","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine, Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"},{"name":"Manchester Centre for Genomic Medicine, St Mary's Hospital Manchester University NHS Foundation Trust, Health Innovation Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Basu","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Lancashire Teaching Hospitals NHS Foundation Trust  Lancashire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.186"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90350-6"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.02.001"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.015"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002740"},{"key":"e_1_2_6_7_1","unstructured":"North East Thames Regional Genetics Service. (2021). Service Pack. Early infantile epileptic encephalopathy. Retrieved fromhttp:\/\/www.labs.gosh.nhs.uk\/laboratory-services\/genetics\/molecular-genetics-service\/molecular-genetics-tests#Panels."},{"key":"e_1_2_6_8_1","unstructured":"Platzer K.&Lemke J. R.(2019).GRIN1\u2010related neurodevelopmental disorder. In M.P. Adam H. H. Ardinger R. A. Pagon et al. (Eds.) GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington Seattle; 1993\u20132021. Retrieved fromhttps:\/\/www.ncbi.nlm.nih.gov\/books\/NBK542807\/."},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.163"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.109.002451"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62528","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62528","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62528","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T23:08:10Z","timestamp":1693004890000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,6]]},"references-count":10,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["10.1002\/ajmg.a.62528"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62528","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,6]]},"assertion":[{"value":"2021-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}