{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T19:06:19Z","timestamp":1774638379499,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2022CFB203"],"award-info":[{"award-number":["2022CFB203"]}],"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;amp; Gen Med"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder. Although individuals with variants in the <jats:italic>SMC1A<\/jats:italic> gene are less commonly seen in CdLS, they exhibit a high incidence of epilepsy and atypical phenotypic variability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The clinical data of a patient with non\u2010classic CdLS and epilepsy caused by an <jats:italic>SMC1A<\/jats:italic> variant were summarized. A literature review was conducted to analyze the genotype\u2013phenotype correlations and epilepsy characteristics in related cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 5\u2010year\u20106\u2010month\u2010old female patient presented with facial features, double outlet right ventricle (DORV), and recurrent epilepsy. Whole exome sequencing (WES) identified a de novo heterozygous frameshift mutation, c.2890_2893del (p.Ser964Valfs*26), in the <jats:italic>SMC1A<\/jats:italic> gene. A review of the literature identified several characteristics of non\u2010classic CdLS with epilepsy caused by <jats:italic>SMC1A<\/jats:italic> variants: the majority of cases were non\u2010classic (81.5%), predominantly female (68.2%), with a median onset age of 11.5\u2009months. Common features included severe\/profound developmental delay (52.6%), hypotonia (18.2%), cardiovascular anomalies (36.4%), and intrauterine growth retardation (IUGR) (22.7%). Among the non\u2010classic cases, seizure clusters occurred in 22.7%, status epilepticus in 18.2%, and drug\u2010resistant epilepsy in 33.3%. Genotypes in non\u2010classic cases included missense mutations (40.9%), frameshift mutations (31.8%), splice site variants (9.1%), nonsense mutations (9.1%), deletions (4.5%), and truncations (4.5%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study expanded the phenotypic data and mutational spectrum of non\u2010classic CdLS with epilepsy caused by <jats:italic>SMC1A<\/jats:italic> variants. Compared to individuals with the classic form of CdLS, the non\u2010classic cases appeared more frequently in females and were associated with a higher prevalence of severe\/profound developmental delay and cardiovascular anomalies. In contrast, IUGR was significantly less common in non\u2010classic individuals. Regarding epilepsy characteristics, some individuals including seizure clusters, status epilepticus, drug resistance, and hypotonia, no significant differences were observed between classic and non\u2010classic cases. The predominant genotypes in non\u2010classic cases were missense and frameshift mutations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70058","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T11:03:36Z","timestamp":1737371016000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A De Novo Frameshift Variant in <scp><i>SMC1A<\/i><\/scp> Causes Non\u2010Classic Cornelia de Lange Syndrome With Epilepsy: A Case Report and Literature Review"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0428-0532","authenticated-orcid":false,"given":"Ying","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Women and Children's Hospital, School of Medicine Xiamen University  Xiamen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenzhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Child Development and Behavior, Women and Children's Hospital, School of Medicine Xiamen University  Xiamen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaling","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, Women and Children's Hospital, School of Medicine Xiamen University  Xiamen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/08830738221081244"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9478"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14040852"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35582"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/511888"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebr.2022.100556"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072\u2010020\u201004559\u20103"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.108069"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36252"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2015.09.007"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0b013e3283645439"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38279"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12729"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576\u2010018\u20100031\u20100"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37364"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.543528"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0578\u20101310.2020.01.016"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn101070\u201020191224\u201001287"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1779"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/ped.15031"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2013.12.008"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13669"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38030"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn101070\u201020200709\u201001152"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn101070\u201020200622\u201001042"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn511374\u201020220125\u201000067"}],"container-title":["Molecular Genetics &amp; 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