{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T06:43:41Z","timestamp":1775976221095,"version":"3.50.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T00:00:00Z","timestamp":1679356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010843","name":"Guangzhou Science, Technology and Innovation Commission","doi-asserted-by":"publisher","award":["202102080455 202102020133"],"award-info":[{"award-number":["202102080455 202102020133"]}],"id":[{"id":"10.13039\/501100010843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> Wiedemann-Steiner syndrome (WSS) is a rare autosomal dominant disorder caused by deleterious heterozygous variants of the <jats:italic>KMT2A<\/jats:italic> gene. This study aims to describe the phenotypic and genotypic features of Chinese WSS patients, and assess therapeutic effects of recombinant human growth hormone (rhGH).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Eleven Chinese children with WSS were enrolled in our cohort. Their clinical, imaging, biochemical and molecular findings were analyzed retrospectively. Moreover, the phenotypic features of 41 previously reported Chinese WSS patients were reviewed and included in our analysis.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> In our cohort, the 11 WSS patients presented with classic clinical manifestations, but with different frequencies. The most common clinical features were short stature (90.9%) and developmental delay (90.9%), followed by intellectual disability (72.7%). The most frequent imaging features were patent ductus arteriosus (57.1%) and patent foramen ovale (42.9%) in cardiovascular system, and abnormal corpus callosum (50.0%) in the brain. In the set comprising 52 Chinese WSS patients, the most common clinical and imaging manifestations were developmental delay (84.6%), intellectual disability (84.6%), short stature (80.8%) and delayed bone age (68.0%), respectively. Eleven different variants, including three known and eight novel variants, of the <jats:italic>KMT2A<\/jats:italic> gene were identified in our 11 WSS patients without a hotspot variant. Two patients were treated with rhGH and yielded satisfactory height gains, but one developed acceleration of bone age.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our study adds 11 new patients with WSS, reveals different clinical characteristics in Chinese WSS patients, and extends the mutational spectrum of the <jats:italic>KMT2A<\/jats:italic> gene. Our study also shares the therapeutic effects of rhGH in two WSS patients without GH deficiency.<\/jats:p>","DOI":"10.3389\/fgene.2023.1085210","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T05:43:37Z","timestamp":1679377417000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Novel variants and phenotypic heterogeneity in a cohort of 11 Chinese children with Wiedemann-Steiner syndrome"],"prefix":"10.3389","volume":"14","author":[{"given":"Yunting","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bobo","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihong","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuzhen","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Yi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huifen","family":"Mei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunhua","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.ejmg.2017.03.006","article-title":"Wiedemann-Steiner syndrome: Novel pathogenic variant and review of literature","volume":"60","author":"Aggarwal","year":"2017","journal-title":"Eur. J. Med. Genet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1111\/cge.13254","article-title":"Wiedemann-Steiner syndrome as a major cause of syndromic intellectual disability: A study of 33 French cases","volume":"94","author":"Baer","year":"2018","journal-title":"Clin. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1007\/s00439-015-1535-8","article-title":"Exome sequencing unravels unexpected differential diagnoses in individuals with the tentative diagnosis of Coffin-Siris and Nicolaides-Baraitser syndromes","volume":"134","author":"Bramswig","year":"2015","journal-title":"Hum. Genet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"514","DOI":"10.3390\/genes13030514","article-title":"KMT2A: Umbrella gene for multiple diseases","volume":"13","author":"Castiglioni","year":"2022","journal-title":"Genes. (Basel)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"119","DOI":"10.3760\/cma.j.cn112140-20210720-00608","article-title":"Analysis of gene variation and clinical characteristics of Wiedemann-Steiner syndrome","volume":"60","author":"Chen","year":"2022","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"B6","doi-asserted-by":"publisher","first-page":"5555","DOI":"10.1007\/s11033-019-04936-y","article-title":"A novel de novo mutation (p.Pro1310Glnfs*46) in KMT2A caused wiedemann-steiner syndrome in a Chinese boy with postnatal growth retardation: A case report","volume":"46","author":"Chen","year":"2019","journal-title":"Mol. Biol. Rep."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.3760\/cma.j.issn.2095-428X.2019.13.016","article-title":"Wiedemann-Steiner syndrome caused by KMT2A gene variation in one child","volume":"34","author":"Dai","year":"2019","journal-title":"Chin. J. Appl. Clin. Pediatr."},{"key":"B8","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1159\/000511971","article-title":"Wiedemann-Steiner syndrome as a differential diagnosis of Cornelia de Lange syndrome using targeted next-generation sequencing: A case report","volume":"12","author":"Demir","year":"2021","journal-title":"Mol. Syndromol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41431-020-0679-8","article-title":"Expanding the phenotype associated to KMT2A variants: Overlapping clinical signs between wiedemann-steiner and rubinstein-taybi syndromes","volume":"29","author":"Di Fede","year":"2021","journal-title":"Eur. J. Hum. Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1111\/cge.14190","article-title":"Neurocognitive and neurobehavioral characterization of two frequent forms of neurodevelopmental disorders: The DYRK1A and the wiedemann-steiner syndromes","volume":"102","author":"Durand","year":"2022","journal-title":"Clin. Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1186\/s13023-021-02018-6","article-title":"Phenotype, genotype and long-term prognosis of 40 Chinese patients with isobutyryl-CoA dehydrogenase deficiency and a review of variant spectra in ACAD8","volume":"16","author":"Feng","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5496\/wjmg.v9.i1.1","article-title":"Clinical and molecular spectrum of Wiedemann-Steiner syndrome, an emerging member of the chromatinopathy family","volume":"9","author":"Fontana","year":"2020","journal-title":"World J. Med. Genet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"3426","DOI":"10.3760\/cma.j.issn.0376-2491.2018.42.010","article-title":"Study of de novo point mutations in known genes among patients with unexplained intellectual disability or developmental delay","volume":"98","author":"Gao","year":"2018","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"B14","doi-asserted-by":"crossref","DOI":"10.1097\/00000441-195909000-00030","volume-title":"Radiographic atlas of skeletal development of the hand and wrist","author":"Greulich","year":"1959"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e19813","DOI":"10.1097\/MD.0000000000019813","article-title":"Wiedemann-steiner syndrome with a de novo mutation in KMT2A: A case report","volume":"99","author":"Jinxiu","year":"2020","journal-title":"Med. Baltim."},{"key":"B16","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.ajhg.2012.06.008","article-title":"De novo mutations in MLL cause Wiedemann-Steiner syndrome","volume":"91","author":"Jones","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.6065\/apem.2244052.026","article-title":"Growth hormone deficiency in a boy with wiedemann-steiner syndrome: A case report and review","author":"Jung","year":"2022","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"B18","doi-asserted-by":"publisher","first-page":"952","DOI":"10.3390\/children8110952","article-title":"Wiedemann-Steiner syndrome with a pathogenic variant in KMT2A from taiwan","volume":"8","author":"Lee","year":"2021","journal-title":"Child. (Basel)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"487","DOI":"10.3760\/cma.j.issn.0578-1310.2009.07.003","article-title":"Height and weight standardized growth charts for Chinese children and adolescents aged 0 to 18 years","volume":"47","author":"Li","year":"2009","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"B20","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/s13023-018-0909-0","article-title":"Description of the molecular and phenotypic spectrum of Wiedemann-Steiner syndrome in Chinese patients","volume":"13","author":"Li","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e001345","DOI":"10.1136\/bmjdrc-2020-001345","article-title":"Molecular and clinical characteristics of monogenic diabetes mellitus in southern Chinese children with onset before 3 years of age","volume":"8","author":"Lin","year":"2020","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e1798","DOI":"10.1002\/mgg3.1798","article-title":"Three de novo variants in KMT2A (MLL) identified by whole exome sequencing in patients with Wiedemann-Steiner syndrome","volume":"9","author":"Luo","year":"2021","journal-title":"Mol. Genet. Genomic Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.1002\/ajmg.a.36590","article-title":"Advanced bone age in a girl with Wiedemann-Steiner syndrome and an exonic deletion in KMT2A (MLL)","author":"Mendelsohn","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"B24","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1111\/cge.12586","article-title":"Delineation of clinical features in Wiedemann-Steiner syndrome caused by KMT2A mutations","volume":"89","author":"Miyake","year":"2016","journal-title":"Clin. Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1007\/s00439-019-01985-y","article-title":"Exploring by whole exome sequencing patients with initial diagnosis of rubinstein-taybi syndrome: The interconnections of epigenetic machinery disorders","volume":"138","author":"Negri","year":"2019","journal-title":"Hum. Genet."},{"key":"B26","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1038\/gim.2015.148","article-title":"Clinical application of whole-exome sequencing across clinical indications","volume":"18","author":"Retterer","year":"2016","journal-title":"Genet. Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"3083","DOI":"10.1093\/hmg\/ddac098","article-title":"Suleiman-el-hattab syndrome: A histone modification disorder caused by TASP1 deficiency","volume":"31","author":"Riedhammer","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"B29","doi-asserted-by":"publisher","first-page":"26","DOI":"10.3760\/cma.j.issn.1000-6699.2019.01.005","article-title":"Wiedemann-Steiner syndrome caused by novel mutation of KMT2A gene: One case report and literature review","volume":"35","author":"Shangguan","year":"2019","journal-title":"Chin. J. Endocrinol. Metab."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1002\/ajmg.a.62124","article-title":"Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome","volume":"185","author":"Sheppard","year":"2021","journal-title":"Am. J. Med. Genet. A"},{"key":"B31","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1530\/EDM-18-0085","article-title":"Growth hormone deficiency as a cause for short stature in Wiedemann-Steiner Syndrome","volume":"2018","author":"Stoyle","year":"2018","journal-title":"Endocrinol. Diabetes Metab. Case Rep."},{"key":"B32","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1002\/ajmg.a.38025","article-title":"Further delineation of the phenotype of truncating KMT2A mutations: The extended Wiedemann-Steiner syndrome","volume":"173","author":"Sun","year":"2017","journal-title":"Am. J. Med. Genet. A"},{"key":"B33","doi-asserted-by":"publisher","first-page":"516","DOI":"10.3760\/cma.j.cn112140-20201231-01145","article-title":"A case of Wiedemann-Steiner syndrome caused by a novel variation of the KMT2A gene","volume":"59","author":"Wang","year":"2021","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e1533","DOI":"10.1002\/mgg3.1533","article-title":"Trio-WES reveals a novel de novo missense mutation of KMT2A in a Chinese patient with wiedemann-steiner syndrome: A case report","volume":"9","author":"Wang","year":"2021","journal-title":"Mol. Genet. Genomic Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"630","DOI":"10.3760\/cma.j.cn511374-20210208-00122","article-title":"Identification of a novel frameshift variant in the KMT2A gene of a child with Wiedemann-Steiner syndrome","volume":"39","author":"Wu","year":"2022","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"B36","doi-asserted-by":"publisher","first-page":"138","DOI":"10.3760\/cma.j.cn511374-20200122-00046","article-title":"Wiedemann-Steiner syndrome due to novel nonsense variant of KMT2A gene in a case","volume":"38","author":"Xue","year":"2021","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.3390\/children9101545","article-title":"Wiedemann-Steiner syndrome: Case report and review of literature","volume":"9","author":"Yu","year":"2022","journal-title":"Child. (Basel)"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1085210\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T05:43:49Z","timestamp":1679377429000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1085210\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,21]]},"references-count":37,"alternative-id":["10.3389\/fgene.2023.1085210"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2023.1085210","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,21]]},"article-number":"1085210"}}