{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T16:37:17Z","timestamp":1773851837850,"version":"3.50.1"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum Genome Var"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Here we report a case of a Japanese girl with Wiedemann\u2013Steiner syndrome carrying a novel heterozygous frameshift variant of\n                    <jats:italic>KMT2A<\/jats:italic>\n                    (NM_001197104.2:c.10123del, p.Thr3375ProfsTer7). Her clinical features included severe pre- and postnatal growth failure, global developmental delay, hypertrichosis and complete agenesis of the corpus callosum. The identified variant truncates the protein, abolishes the C-terminal SET domain required for histone methyltransferase activity, and is predicted to trigger nonsense-mediated mRNA decay, resulting in\n                    <jats:italic>KMT2A<\/jats:italic>\n                    haploinsufficiency\u2014the primary pathogenic mechanism of Wiedemann\u2013Steiner syndrome. This report documents a previously unreported loss-of-function variant in\n                    <jats:italic>KMT2A<\/jats:italic>\n                    with detailed molecular interpretation and phenotypic characterization, contributing to refinement of the mutational spectrum associated with Wiedemann\u2013Steiner syndrome.\n                  <\/jats:p>","DOI":"10.1038\/s41439-026-00338-2","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:05:40Z","timestamp":1773763540000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heterozygous frameshift KMT2A variant in a patient with Wiedemann\u2013Steiner syndrome"],"prefix":"10.1038","volume":"13","author":[{"given":"Sawako","family":"Hirai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Mitsubuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirou","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"338_CR1","unstructured":"Wiedemann, H. R., Kunze, J., Grosse, F. R. & Dibbern, H. In Atlas of Clinical Syndromes. A Visual Aid to Diagnosis for Clinicians and Practicing Physicians 2nd edn 198\u2013199 (Wolfe Publishing, 1989)."},{"key":"338_CR2","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1097\/00019605-200009020-00021","volume":"9","author":"CE Steiner","year":"2000","unstructured":"Steiner, C. E. & Marques, A. P. Growth deficiency, mental retardation and unusual facies. Clin. Dysmorphol. 9, 155\u2013156 (2000).","journal-title":"Clin. Dysmorphol."},{"key":"338_CR3","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.ajhg.2012.06.008","volume":"91","author":"WD Jones","year":"2012","unstructured":"Jones, W. D. et al. De novo mutations in MLL cause Wiedemann\u2013Steiner syndrome. Am. J. Hum. Genet. 91, 358\u2013364 (2012).","journal-title":"Am. J. Hum. Genet."},{"key":"338_CR4","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41525-019-0083-x","volume":"4","author":"AJS Chan","year":"2019","unstructured":"Chan, A. J. S. et al. Expanding the neurodevelopmental phenotypes of individuals with de novo KMT2A variants. npj Genom. Med. 4, 9 (2019).","journal-title":"npj Genom. Med."},{"key":"338_CR5","unstructured":"Sheppard SE, Quintero-Rivera F. Wiedemann-Steiner Syndrome. In (eds Adam MP, Feldman J, Mirzaa GM, et al.) GeneReviews\u00ae [Internet]. Seattle (WA), 1993\u20132025 (University of Washington, Seattle 2022). Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK580718\/."},{"key":"338_CR6","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1002\/ajmg.a.62124","volume":"185","author":"S E Sheppard","year":"2021","unstructured":"Sheppard, S. E. et al. Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome. Am. J. Med. Genet. A. 185, 1649\u20131665 (2021).","journal-title":"Am. J. Med. Genet. A."},{"key":"338_CR7","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1111\/cge.13254","volume":"94","author":"S Baer","year":"2018","unstructured":"Baer, S. et al. Wiedemann\u2013Steiner syndrome as a major cause of syndromic intellectual disability: a study of 33 French cases. Clin. Genet. 94, 141\u2013152 (2018).","journal-title":"Clin. Genet."},{"key":"338_CR8","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.3390\/children9101545","volume":"9","author":"H Yu","year":"2022","unstructured":"Yu, H., Zhang, G., Yu, S. & Wu, W. Wiedemann\u2013Steiner syndrome: case report and review of literature. Children 9, 1545 (2022).","journal-title":"Children"},{"key":"338_CR9","doi-asserted-by":"publisher","first-page":"e19813","DOI":"10.1097\/MD.0000000000019813","volume":"99","author":"J Liu","year":"2020","unstructured":"Liu, J., Liang, S., Xue, M., Liu, C. S. J., Liu, X. & Duan, W. Wiedemann\u2013Steiner syndrome with a de novo mutation in KMT2A: a case report. Medicine 99, e19813 (2020).","journal-title":"Medicine"},{"key":"338_CR10","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/s41431-017-0033-y","volume":"26","author":"N Lebrun","year":"2018","unstructured":"Lebrun, N. et al. Molecular and cellular issues of KMT2A variants involved in Wiedemann\u2013Steiner syndrome. Eur. J. Hum. Genet. 26, 107\u2013116 (2018).","journal-title":"Eur. J. Hum. Genet."},{"key":"338_CR11","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.2415","volume":"12","author":"J Niu","year":"2024","unstructured":"Niu, J., Teng, X. & Zhang, J. Aberrant splicing caused by a novel KMT2A variant in Wiedemann\u2013Steiner syndrome. Mol. Genet. Genomic Med. 12, e2415 (2024).","journal-title":"Mol. Genet. Genomic Med."}],"container-title":["Human Genome Variation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41439-026-00338-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41439-026-00338-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41439-026-00338-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T10:20:08Z","timestamp":1773829208000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41439-026-00338-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,17]]},"references-count":11,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["338"],"URL":"https:\/\/doi.org\/10.1038\/s41439-026-00338-2","relation":{},"ISSN":["2054-345X"],"issn-type":[{"value":"2054-345X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,17]]},"assertion":[{"value":"30 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Written informed consent for publication, including the use of identifiable photographs and clinical information, was obtained from the patient\u2019s parents.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"6"}}