{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T08:46:06Z","timestamp":1783068366380,"version":"3.54.6"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010849","name":"Health and Family Planning Commission of Wuhan Municipality","doi-asserted-by":"publisher","award":["WX14A06"],"award-info":[{"award-number":["WX14A06"]}],"id":[{"id":"10.13039\/501100010849","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010849","name":"Health and Family Planning Commission of Wuhan Municipality","doi-asserted-by":"publisher","award":["WX16C17"],"award-info":[{"award-number":["WX16C17"]}],"id":[{"id":"10.13039\/501100010849","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010849","name":"Health and Family Planning Commission of Wuhan Municipality","doi-asserted-by":"publisher","award":["WX17Z12"],"award-info":[{"award-number":["WX17Z12"]}],"id":[{"id":"10.13039\/501100010849","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2017CFB322"],"award-info":[{"award-number":["2017CFB322"]}],"id":[{"id":"10.13039\/501100003819","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":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Wiedemann\u2013Steiner syndrome (WSS) is an autosomal dominant disorder characterized by short stature, hypertrichosis, intellectual disability, developmental delay, along with facial dysmorphism. WSS patients exhibit great phenotypic heterogeneities. Some variants in <jats:italic>KMT2A<\/jats:italic> (<jats:italic>MLL<\/jats:italic>) gene have been identified as the cause of WSS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole exome sequencing on the probands followed by Sanger sequencing validations in the family were applied to determine genetic variants. In silico analyses were used for predicting potential effects of the variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified three novel <jats:italic>de novo<\/jats:italic> heterozygous variants: c.883A&gt;T (p.Lys295*), c.4171C&gt;T (p.Gln1391*), and c.3499T&gt;C (p.Cys1167Arg), in <jats:italic>KMT2A<\/jats:italic> gene from three unrelated Chinese WSS patients. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, these three variants were classified as pathogenic, pathogenic and likely pathogenic variant, respectively. By reviewing all the available cases with same mutated KMT2A regions as the three patients had, we found that in addition to the representative symptoms, our patients exhibited some sporadically observed symptoms, such as severe ophthalmological symptoms, endocardial fibroelastosis, cytomegalovirus infection, and feet eversion. We also revealed that variants in different KMT2A regions contribute to the phenotypic heterogeneity of WSS, highlighting challenges in the diagnosis of syndromic disorders spanning a broad phenotypic spectrum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study would aid in further broadening our knowledge about the genotype\u2013phenotype correlation of WSS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1798","type":"journal-article","created":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T14:38:45Z","timestamp":1630507125000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Three <i>de novo<\/i> variants in <i>KMT2A<\/i> (<i>MLL<\/i>) identified by whole exome sequencing in patients with Wiedemann\u2013Steiner syndrome"],"prefix":"10.1002","volume":"9","author":[{"given":"Sukun","family":"Luo","sequence":"first","affiliation":[{"name":"Precision Medical Laboratory Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital) Tongji Medical College Huazhong University of Science &amp; Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Bi","sequence":"additional","affiliation":[{"name":"Rehabilitation Department Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital) Tongji Medical College Huazhong University of Science &amp; Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqian","family":"Zhang","sequence":"additional","affiliation":[{"name":"BGI Genomics BGI\u2010Shenzhen Shenzhen China"},{"name":"BGI\u2010Wuhan Clinical Laboratories BGI\u2010Shenzhen Wuhan China"},{"name":"Department of Biology University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhou","sequence":"additional","affiliation":[{"name":"BGI Genomics BGI\u2010Shenzhen Shenzhen China"},{"name":"BGI\u2010Wuhan Clinical Laboratories BGI\u2010Shenzhen Wuhan China"},{"name":"State Key Laboratory of Agricultural Microbiology College of Life Science and Technology Huazhong Agricultural University Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"BGI Genomics BGI\u2010Shenzhen Shenzhen China"},{"name":"BGI\u2010Wuhan Clinical Laboratories BGI\u2010Shenzhen Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiwei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Precision Medical Laboratory Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital) Tongji Medical College Huazhong University of Science &amp; Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Precision Medical Laboratory Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital) Tongji Medical College Huazhong University of Science &amp; Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yuan","sequence":"additional","affiliation":[{"name":"Ultrasonography Department Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital) Tongji Medical College Huazhong University of Science &amp; Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6275-1219","authenticated-orcid":false,"given":"Xuelian","family":"He","sequence":"additional","affiliation":[{"name":"Precision Medical Laboratory Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital) Tongji Medical College Huazhong University of Science &amp; Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-015-0522-5"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13254"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02434-4"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.1438"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41525-019-0083-x"},{"issue":"6","key":"e_1_2_10_7_1","first-page":"301","article-title":"Measurements of echocardiography in 1344 healthy children","volume":"17","author":"Deng H. Y.","year":"2006","journal-title":"Journal of China Clinic Medical Imaging"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38405"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61407"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1978.03910050554013"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.06.008"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-017-0033-y"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-018-0909-0"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.09.025"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1047951110000181"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404150"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00741-4"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073816674095"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12586"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22666"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3413"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37681"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-15-49"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.423855"},{"key":"e_1_2_10_25_1","first-page":"198","volume-title":"A syndrome of abnormal facies, short stature, and psychomotor retardation Atlas of Clinical Syndromes: A Visual Aid to Diagnosis for Clinicians and Practicing Physicians","author":"Wiedemann H. R.","year":"1989"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2017.11.022"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.14.7286"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.22.10610"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1798","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.1798","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1798","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T12:38:14Z","timestamp":1693226294000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.1798"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":27,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/mgg3.1798"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.1798","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9]]},"assertion":[{"value":"2021-03-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1798"}}