{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T15:47:05Z","timestamp":1793029625429,"version":"4.5.0"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Rauch\u2013Steindl syndrome (RAUST) is a very rare genetic syndrome caused by a pathogenic variant in <jats:italic>NSD2<\/jats:italic> on chromosome 4p16.3. Although <jats:italic>NSD2<\/jats:italic> was previously thought to be the major gene in Wolf\u2013Hirschhorn syndrome (WHS), a contiguous gene syndrome of chromosome 4p16.3 deletion, RAUST has been found to present different facial and clinical features from WHS. In this study, we report the details of two newly diagnosed individuals with RAUST in order to better understand the molecular and clinical features of RAUST.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010genome sequencing was performed on two individuals with psychomotor delay and growth failure. Detailed clinical evaluation of growth parameters, craniofacial features, electroencephalogram (EEG), magnetic resonance imaging of the brain, and developmental assessment were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both individuals had de novo truncating variants in <jats:italic>NSD2<\/jats:italic>. One had a novel variant (c.2470C&gt;T, p.Arg824*), and the other had a recurrent variant (c.4028del, p.Pro1343Glnfs*49). Both exhibited characteristic RAUST facial features, growth failure, and mild psychomotor delay. A novel finding of RAUST was seen in individual 2, a Chiari malformation type 1, and both showed delayed bone age. They lacked common WHS features such as congenital heart defects, cleft lip\/palate, and seizures (EEG with abnormal findings).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We present a novel variant and clinical presentations of RAUST, expand the molecular and clinical diversity of RAUST, and improve our understanding of this rare syndrome, which is distinct from WHS. Further researches are needed on more RAUST cases and on functional analysis of <jats:italic>NSD2<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2396","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T09:40:02Z","timestamp":1707903602000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Clinical details of individuals with Rauch\u2013Steindl syndrome due to <scp><i>NSD2<\/i><\/scp> truncating variants"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7993-1964","authenticated-orcid":false,"given":"Eriko","family":"Nishi","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Osaka Women's and Children's Hospital  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumiko","family":"Yanagi","sequence":"additional","affiliation":[{"name":"Department of Genome Medicine National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0281-9610","authenticated-orcid":false,"given":"Tadashi","family":"Kaname","sequence":"additional","affiliation":[{"name":"Department of Genome Medicine National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Osaka Women's and Children's Hospital  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,14]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a004044"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30187"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31449"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40498"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010018\u20100014\u20108"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920\u2010020\u201000831\u20109"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881\u2010019\u20100863\u20102"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440\u20101819.2009.01931.x"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038\u2010018\u20100464\u20105"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1022683"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35910"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13173"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1064783"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010021\u201001158\u20101"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2396","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T06:56:35Z","timestamp":1717138595000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2396"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2]]},"references-count":15,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/mgg3.2396"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2396","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2]]},"assertion":[{"value":"2023-10-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2396"}}