{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:12:37Z","timestamp":1788423157673,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":245,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFC2707001"],"award-info":[{"award-number":["2024YFC2707001"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFC2707000"],"award-info":[{"award-number":["2024YFC2707000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Prenatal phenotypic manifestations of genetic disorders associated with\n                      <jats:italic>NSD2<\/jats:italic>\n                      variants remain poorly characterized. This study presents our institutional experience with the prenatal diagnosis of\n                      <jats:italic>NSD2<\/jats:italic>\n                      \u2010associated genetic disorders, specifically Rauch\u2013Steindl syndrome (RAUST), aiming to improve understanding of both the molecular and clinical features of RAUST.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed a retrospective analysis of six fetuses and one adult diagnosed with RAUST at our institution and thoroughly reviewed the prenatal ultrasound reports of six fetuses. Prenatal and postnatal phenotypes of RAUST cases were summarized alongside findings from previously published literature. Correlations between NSD2 variant locations, variant types, and phenotypes were analyzed. Additionally, protein modeling was used to visualize structural changes in NSD2 protein before and after C\u2010terminal variants. We integrated single\u2010cell transcriptomic and gene expression data from multiple public databases to investigate spatiotemporal expression patterns of\n                      <jats:italic>NSD2<\/jats:italic>\n                      during human fetal development.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fetal growth restriction (FGR) was the most prevalent prenatal manifestation in RAUST fetuses, followed by microcephaly. Bilateral renal hypoplasia emerged as a novel prenatal ultrasonographic feature. Postnatally, speech and motor developmental delays were the most commonly reported phenotypes, followed by physical developmental delays and intellectual disability. Genotype\u2010phenotype correlation analysis revealed an association between N\u2010terminal truncating variants in NSD2 and impaired fetal growth parameters. Notably, C\u2010terminal truncating variants\u2014predicted not to directly impact NSD2 functional domains\u2014also exerted disease\u2010causing effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study provides a comprehensive analysis of prenatal phenotypes in RAUST cases, enriching the prenatal phenotypic spectrum of the disease and facilitating early diagnosis and clinical management of RAUST. Furthermore, our genotype\u2010phenotype correlation findings lay a foundational basis for future research into the complex molecular mechanisms underlying\n                      <jats:italic>NSD2<\/jats:italic>\n                      \u2010associated genetic disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/humu\/1637135","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:18:13Z","timestamp":1788419893000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenotypes of Hereditary Diseases Associated With Rauch\u2013Steindl Syndrome"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9816-8869","authenticated-orcid":false,"given":"Yi","family":"Kong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4029-032X","authenticated-orcid":false,"given":"Yousheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0953-0764","authenticated-orcid":false,"given":"Xingwang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9501-5031","authenticated-orcid":false,"given":"Jianhong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaolan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8062-2780","authenticated-orcid":false,"given":"Wanfang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiling","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3628-9382","authenticated-orcid":false,"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-018-0464-5"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1064783"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01158-1"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2011.08.042"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40498"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.2396"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/uog.5192"},{"key":"e_1_2_11_8_2","first-page":"384","article-title":"A Validation Study of Ultrasonic Foetal Weight Estimation Models for Hong Kong Chinese Singleton Pregnancies","volume":"10","author":"Pang M. W.","year":"2004","journal-title":"Hong Kong Medical Journal"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1132"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu457"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz828"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1008667"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt473"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky427"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0690-5"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000004252"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/uog.22134"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2021.1926450"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2014.03.047"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2017.05.001"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c00948"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S259873"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-1000"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2009.05.038"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13072-022-00446-7"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03069-8"},{"key":"e_1_2_11_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-019-0863-2"},{"key":"e_1_2_11_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/wdev.89"},{"key":"e_1_2_11_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.11.016"},{"key":"e_1_2_11_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/database\/bau092"},{"key":"e_1_2_11_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2024.100767"},{"key":"e_1_2_11_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02807-z"},{"key":"e_1_2_11_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.04.069"},{"key":"e_1_2_11_34_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190832"}],"container-title":["Human Mutation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/humu\/1637135","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/humu\/1637135","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/humu\/1637135","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:18:15Z","timestamp":1788419895000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/humu\/1637135"}},"subtitle":[],"editor":[{"given":"Baisakhi","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/humu\/1637135"],"URL":"https:\/\/doi.org\/10.1155\/humu\/1637135","archive":["Portico"],"relation":{},"ISSN":["1059-7794","1098-1004"],"issn-type":[{"value":"1059-7794","type":"print"},{"value":"1098-1004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-08-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1637135"}}