{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T22:27:29Z","timestamp":1773872849185,"version":"3.50.1"},"reference-count":16,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:00:00Z","timestamp":1710460800000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["19ZR1462300"],"award-info":[{"award-number":["19ZR1462300"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Wiedemann\u2013Steiner syndrome (WSS) is a rare autosomal\u2010dominant disorder caused by <jats:italic>KMT2A<\/jats:italic> variants. The aim of this study was to characterize a novel <jats:italic>KMT2A<\/jats:italic> variant in a child with WSS and demonstrate integrated diagnostic approaches.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A 3\u2010year\u2010old female with developmental delay, distinctive facial features, and anal fistula underwent whole exome sequencing (WES). RNA analysis was performed to assess splicing effects caused by a novel variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>WES identified novel heterozygous <jats:italic>KMT2A<\/jats:italic> c.5664+6T&gt;C variant initially classified as a variant of uncertain significance. RNA analysis provided evidence of aberrant splicing (exon 20 skipping), allowing reclassification to likely pathogenic. The patient exhibited typical WSS features along with a potential novel finding of anal fistula.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This report describes a novel non\u2010canonical splice site variant in <jats:italic>KMT2A<\/jats:italic> associated with WSS. RNA analysis was critical for variant reclassification. Detailed phenotypic evaluation revealed common and expanded WSS manifestations. This case highlights the importance of combining clinical assessment, DNA testing, and RNA functional assays for the diagnosis of rare genetic disorders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2415","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T06:41:48Z","timestamp":1710571308000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Aberrant splicing caused by a novel <i>KMT2A<\/i> variant in <scp>Wiedemann\u2013Steiner<\/scp> syndrome"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9244-0184","authenticated-orcid":false,"given":"Jianing","family":"Niu","sequence":"first","affiliation":[{"name":"Reproductive Medicine Center, Shanghai First Maternity and Infant Hospital, School of Medicine Tongji University  Shanghai China"},{"name":"Department of Obstetrics and Gynecology, Jiaxing Maternity and Child Health Care Hospital, College of Medicine Jiaxing University  Jiaxing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoming","family":"Teng","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Shanghai First Maternity and Infant Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0239-6670","authenticated-orcid":false,"given":"Junyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, Shanghai First Maternity and Infant Hospital, School of Medicine Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30400"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1877"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.5496\/wjmg.v9.i1.1"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.06.008"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrdd.20140"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12586"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.1.1.461"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62124"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019605\u2010200009020\u201000021"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010020\u20100766\u20109"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.06.002"},{"key":"e_1_2_11_14_1","unstructured":"Wiedemann H.\u2010R. Kunze J. Grosse F. &Dibbern H.(1989).A\u00a0syndrome of abnormal facies short stature and psychomotor retardation. Atlas of clinical syndromes: A visual aid to diagnosis for clinicians and practicing physicians (2nd ed.) London: Wolfe Publishing Ltd. (pub.) 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