{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T19:39:40Z","timestamp":1780515580893,"version":"3.54.1"},"reference-count":17,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["PO2366\/2\u20101"],"award-info":[{"award-number":["PO2366\/2\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    NSD2 dimethylates histone H3 at lysine 36 (H3K36me2) and is located in the Wolf\u2010Hirschhorn syndrome (WHS) critical region. Recent descriptions have delineated loss\u2010of\u2010function (LoF) variants in\n                    <jats:italic>NSD2<\/jats:italic>\n                    with a distinct disorder. The oncogenic missense variant p.Glu1099Lys occurs somatically in leukemia and has a gain\u2010of\u2010function (GoF) effect. We describe two individuals carrying p.Glu1099Lys as heterozygous de novo germline variant identified by exome sequencing (ES) of blood DNA and subsequently confirmed in two ectodermal tissues. Clinically, these individuals are characterized by intellectual disability, coarse\/ square facial gestalt, abnormalities of the hands, and organomegaly. Public cell lines with NSD2 GoF variants had increased K36me2, DNA promoter methylation, and dysregulated RNA expression. NSD2 GoF caused by p.Glu1099Lys is associated with a novel phenotype different from WHS and Rauch\u2013Steindl syndrome (RAUST).\n                  <\/jats:p>","DOI":"10.1111\/cge.14241","type":"journal-article","created":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T04:20:52Z","timestamp":1664770852000},"page":"226-230","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The constitutional gain\u2010of\u2010function variant p.\n                    <scp>Glu1099Lys<\/scp>\n                    in\n                    <i>NSD2<\/i>\n                    is associated with a novel syndrome"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3679-1081","authenticated-orcid":false,"given":"Bernt","family":"Popp","sequence":"first","affiliation":[{"name":"Institute of Human Genetics University of Leipzig Medical Center  Leipzig Germany"},{"name":"Berlin Institute of Health at Charit\u00e9 Universit\u00e4tsmedizin Berlin, Center of Functional Genomics  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6920-8550","authenticated-orcid":false,"given":"Melanie","family":"Brugger","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibylle","family":"Poschmann","sequence":"additional","affiliation":[{"name":"Division of Neuropediatrics Clinic for Children and Adolescents Dritter Orden  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5406-0776","authenticated-orcid":false,"given":"Tobias","family":"Bartolomaeus","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Leipzig Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0150-9709","authenticated-orcid":false,"given":"Maximilian","family":"Radtke","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Leipzig Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5706-1424","authenticated-orcid":false,"given":"Julia","family":"Hentschel","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Leipzig Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9439-4677","authenticated-orcid":false,"given":"Nataliya","family":"Di Donato","sequence":"additional","affiliation":[{"name":"Institute for Clinical Genetics, University Hospital TU Dresden  Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7116-6364","authenticated-orcid":false,"given":"Andreas","family":"Rump","sequence":"additional","affiliation":[{"name":"Institute for Clinical Genetics, University Hospital TU Dresden  Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janina","family":"Gburek\u2010Augustat","sequence":"additional","affiliation":[{"name":"Division of Neuropaediatrics, Hospital for Children and Adolescents University of Leipzig Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1119-2285","authenticated-orcid":false,"given":"Elisabeth","family":"Graf","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4454-8823","authenticated-orcid":false,"given":"Matias","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine Technical University of Munich  Munich Germany"},{"name":"Institute of Neurogenomics Helmholtz Zentrum M\u00fcnchen  Neuherberg Germany"},{"name":"Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics, Department of Pediatrics, Dr. von Hauner Children's Hospital Munich University Hospital (Ludwig Maximilians University)  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8992-5637","authenticated-orcid":false,"given":"Ina","family":"Sorge","sequence":"additional","affiliation":[{"name":"Department of Pediatric Radiology University of Leipzig  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4435-6610","authenticated-orcid":false,"given":"Johannes R","family":"Lemke","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Leipzig Medical Center  Leipzig Germany"},{"name":"Center of Rare Diseases University of Leipzig Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8838-8403","authenticated-orcid":false,"given":"Thomas","family":"Meitinger","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1542-1399","authenticated-orcid":false,"given":"Rami","family":"Abou Jamra","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Leipzig Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1361-7766","authenticated-orcid":false,"given":"Vincent","family":"Strehlow","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Leipzig Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5183-780X","authenticated-orcid":false,"given":"Theresa","family":"Brunet","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine Technical University of Munich  Munich Germany"},{"name":"Institute of Neurogenomics Helmholtz Zentrum M\u00fcnchen  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz174"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-07-298349"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.7.1071"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30190"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01158-1"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.9.3025"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.204"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11003"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.08.042"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03069-8"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26913-5"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.04.015"},{"key":"e_1_2_9_14_1","volume-title":"GeneReviews\u00ae","author":"Pappas J","year":"1993"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2017-104574"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37995"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-141054"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-20-0092"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14241","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.14241","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14241","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T09:27:45Z","timestamp":1692523665000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,20]]},"references-count":17,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["10.1111\/cge.14241"],"URL":"https:\/\/doi.org\/10.1111\/cge.14241","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.02.23.22271353","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14241\/v3\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14241\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14241\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14241\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14241\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14241\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14241\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14241\/v1\/review3","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,20]]},"assertion":[{"value":"2022-07-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}