{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T14:08:26Z","timestamp":1774793306900,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T00:00:00Z","timestamp":1715385600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["232300421289"],"award-info":[{"award-number":["232300421289"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81701125"],"award-info":[{"award-number":["81701125"]}],"id":[{"id":"10.13039\/501100001809","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":[[2024,5]]},"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, and cases caused by variants in the structural maintenance of chromosomes protein 3 (<jats:italic>SMC3<\/jats:italic>) gene are uncommon. Here, we report two cases of CdLS associated with novel pathogenic variants in <jats:italic>SMC3<\/jats:italic> from two Chinese families.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical presentations of two patients with CdLS were evaluated, and specimens from the patients and other family members were collected for Trio\u2010based whole\u2010exome sequencing. Pyrosequencing, chip\u2010based digital PCR, minigene splicing assay, and in silico analysis were carried out to elucidate the impact of novel variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Novel heterozygous variants in <jats:italic>SMC3<\/jats:italic> were identified in each proband. One harbored a novel splicing and mosaic variant (c.2535+1G&gt;A) in <jats:italic>SMC3<\/jats:italic>. The mutated allele G&gt;A conversion was approximately 23.1% by digital PCR, which indicated that 46.2% of peripheral blood cells had this variant. Additionally, in\u00a0vitro minigene splicing analysis validated that the c.2535+1G&gt;A variant led to an exon skipping in messenger RNA splicing. The other carried a heterozygous variant (c.435C&gt;A), which was predicted to be pathogenic as well as significantly altered in local electrical potential. The former showed multiple abnormalities and marked clinical severity, and the latter mainly exhibited a speech developmental disorder and slightly facial anomalies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Both patients were clinically diagnosed with Cornelia de Lange syndrome 3 (CdLS3). The newly identified <jats:italic>SMC3<\/jats:italic> gene variants can expand the understanding of CdLS3 and provide reliable evidence for genetic counseling to the affected family.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2447","type":"journal-article","created":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T07:58:53Z","timestamp":1715414333000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of two novel heterozygous variants of <i>SMC3<\/i> with Cornelia de Lange syndrome"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4224-7023","authenticated-orcid":false,"given":"Zhi","family":"Lei","sequence":"first","affiliation":[{"name":"Henan Key Laboratory of Children's Genetics and Metabolic Diseases Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital Zhengzhou Children's Hospital  Zhengzhou Henan 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