{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:25:03Z","timestamp":1773278703419,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>KCNT2<\/jats:italic>\n                    variants resulting in substitutions affecting the Arg190 residue have been shown to cause epileptic encephalopathy and a recognizable facial gestalt. We report two additional individuals with intellectual disability, dysmorphic features, hypertrichosis, macrocephaly and the same de novo\n                    <jats:italic>KCNT2<\/jats:italic>\n                    missense variants affecting the Arg190 residue as previously described. Notably, neither patient has epilepsy. Homology modeling of these missense variants revealed that they are likely to disrupt the stabilization of a closed channel conformation of KCNT2 resulting in a constitutively open state. This is the first report of pathogenic variants in\n                    <jats:italic>KCNT2<\/jats:italic>\n                    causing a developmental phenotype without epilepsy.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.62370","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T21:01:18Z","timestamp":1622581278000},"page":"3083-3091","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Recurrent\n                    <scp>\n                      <i>KCNT2<\/i>\n                    <\/scp>\n                    missense variants affecting p.Arg190 result in a recognizable phenotype"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3674-3960","authenticated-orcid":false,"given":"Adam","family":"Jackson","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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1196-3000","authenticated-orcid":false,"given":"Helen","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Oxford Centre for Genomic Medicine, Oxford Radcliffe Hospitals NHS Trust, Nuffield Orthopaedic Hospital  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Genomics England Research Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Peninsula Clinical Genetics Exeter Genomics Laboratory, Royal Devon and Exeter NHS Foundation Trust  Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Lovell","sequence":"additional","affiliation":[{"name":"Division of Evolution and Genomic Sciences School of Biological Sciences, University of Manchester  Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill","family":"Clayton\u2010Smith","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":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,6,1]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.18388\/abp.2020_5364"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25248"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2013.166"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000363"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-37-11681.2003"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20462"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.262725"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12499788"},{"key":"e_1_2_9_10_1","unstructured":"CaulfieldM DaviesJ DennysM ElbahyL FowlerT HillS HubbardT JostinsL MaltbyN Mahon\u2010PearsonJ McVeanG Nevin\u2010RidleyK ParkerM ParryV RendonA RileyL TurnbullC WoodsK.2019.The National Genomics Research and Healthcare Knowledgebase."},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5978-08.2009"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.250"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200910316"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi0506s15"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2017.03.035"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.11.013"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50847"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.09.088"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057115601677"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2020.05.003"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/1074248417729880"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/354262"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.00614"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2014.10.030"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2020.00001"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu030"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.15216"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2440"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2012.04.006"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.75"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S214907"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.01.038"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.643536"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1177\/1179069517726996"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan2507"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0923-1811(90)90130-6"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz291"}],"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.62370","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62370","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62370","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:54:28Z","timestamp":1773226468000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62370"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,1]]},"references-count":38,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/ajmg.a.62370"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62370","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,1]]},"assertion":[{"value":"2021-01-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}