{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T12:46:09Z","timestamp":1782305169461,"version":"3.54.5"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"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":["2022YFC2705202"],"award-info":[{"award-number":["2022YFC2705202"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"publisher","award":["2024ZZ2005"],"award-info":[{"award-number":["2024ZZ2005"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Rauch\u2010Steindl syndrome (RAUST) is a rare neurodevelopmental disorder caused by pathogenic variants in\n                      <jats:italic>NSD2<\/jats:italic>\n                      , a histone methyltransferase gene at 4p16.3. Due to phenotypic overlap with Wolf\u2010Hirschhorn syndrome (WHS), RAUST is often misdiagnosed. Missense variants in\n                      <jats:italic>NSD2<\/jats:italic>\n                      are particularly challenging to interpret without functional validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Genomic DNA from the proband and her parents was extracted from peripheral blood. Trio\u2010whole\u2010exome sequencing (WES) was performed to identify candidate variants based on the clinical phenotype, followed by Sanger sequencing validation. RNA splicing impact was assessed via reverse transcription PCR and TA\u2010cloning from peripheral blood mononuclear cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A 7\u2010year\u20108\u2010month\u2010old girl mainly presented with intrauterine and postnatal growth restriction, global developmental delay, intellectual disability, epilepsy, short stature, and facial dysmorphism was documented. Trio\u2010WES identified a novel\n                      <jats:italic>de novo<\/jats:italic>\n                      missense variant in\n                      <jats:italic>NSD2<\/jats:italic>\n                      (NM_001042424.3: c.2137G&gt;C, p.Gly713Arg), which is located at the last base of exon 11 and was predicted to be highly likely to cause aberrant splicing. Functional analysis revealed this variant causes exon 11 skipping in 53% of transcripts, resulting in a frameshift (p.Leu672Glyfs*20) and premature truncation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This is the first report of an\n                      <jats:italic>NSD2<\/jats:italic>\n                      missense variant that functionally acts as a splicing mutation leading to protein truncation. Our findings highlight the necessity of RNA\u2010level functional assays for accurate variant interpretation and reinforce genotype\u2013phenotype distinctions between RAUST and WHS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70238","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T05:30:45Z","timestamp":1780119045000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and Functional Analysis of a Novel\n                    <i>NSD2<\/i>\n                    Missense Variant in a Patient With Rauch\u2010Steindl Syndrome"],"prefix":"10.1002","volume":"14","author":[{"given":"Shixuan","family":"Xu","sequence":"first","affiliation":[{"name":"The International Peace Maternity and Child Health Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases  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