{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T11:37:17Z","timestamp":1760441837460,"version":"3.41.2"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cornelia de Lange syndrome (CdLS) is an uncommon congenital developmental disorder distinguished by intellectual disorder and distinctive facial characteristics, with a minority of cases attributed to <jats:italic>RAD21<\/jats:italic> variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A patient was admitted to the endocrinology department at Peking Union Medical College Hospital, where 2\u2009mL of peripheral venous blood was collected from the patient and his parents. DNA was extracted for whole\u2010exome sequencing (WES) analysis, and the genetic variation of the parents was confirmed through Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 13.3\u2010year\u2010old male patient with a height of 136.5\u2009cm (\u22123.5 SDS) and a weight of 28.4\u2009kg (\u22123.1 SDS) was found to have typical craniofacial features. WES revealed a pathogenic variant c.1143G&gt;A (p.Trp381*) in the <jats:italic>RAD21<\/jats:italic> gene. He was diagnosed with CdLS type 4 (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.omim.org\/entry\/614701?search=614701&amp;highlight=614701\">OMIM #614701<\/jats:ext-link>). We reviewed 36 patients with CdLS related to <jats:italic>RAD21<\/jats:italic> gene variants reported worldwide from May 2012 to March 2024. Patient's variant status, clinical characteristics, and rhGH treatment response were summarized. Frameshift variants constituted the predominant variant type, representing 36% (13\/36) of cases. Clinical features included verbal developmental delay and intellectual disorder observed in 94% of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study reported the third case of CdLS type 4 in China caused by a <jats:italic>RAD21<\/jats:italic> gene variant, enriching the genetic mutational spectrum.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70009","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T18:08:28Z","timestamp":1726596508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Characteristics, Genetic Analysis, and Literature Review of Cornelia de Lange Syndrome Type 4 Associated With a <scp><i>RAD21<\/i><\/scp> Variant"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3296-0473","authenticated-orcid":false,"given":"Xinyu","family":"Yue","sequence":"first","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1998-9915","authenticated-orcid":false,"given":"Meiping","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoan","family":"Ke","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key 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