{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:59:13Z","timestamp":1788973153947,"version":"build-2803163510"},"reference-count":18,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder that affects many organs. The diagnosis of this condition is primarily clinical and it can be confirmed by molecular analysis of the genes known to cause this disease, although about 30% of CdLS patients are without a genetic diagnosis. Here we report clinical and genetic findings of a patient with CdLS type 4, a syndrome of which the clinical features of only 30 patients have been previously described in the literature. The index patient presented with clinical characteristics previously associated with CdLS type 4 (short nose, thick eyebrow, global development delay, synophrys, microcephaly, weight &lt; 2DS, small hands, height &lt; 2DS). She also presented cardiac anomalies, cleft palate and laryngomalacia, which was never described before. The index patient was diagnosed with a novel de novo\u00a0RAD21 variant (c.1722_1723delTG, p.Gly575SerfsTer2): segregation analysis, bioinformatic analysis, population data and in silico structural modelling indicate the pathogenicity of the novel variant. This report summarizes previously reported clinical manifestations of CdLS type 4 but also highlights new clinical symptoms, which will aid correct counselling of future CdLS type 4 cases.<\/jats:p>","DOI":"10.3390\/genes14010119","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T02:12:48Z","timestamp":1672625568000},"page":"119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Novel Variant in RAD21 in Cornelia De Lange Syndrome Type 4: Case Report and Bioinformatic Analysis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1569-1556","authenticated-orcid":false,"given":"Alessandro","family":"De Falco","sequence":"first","affiliation":[{"name":"U.O.C. Genetica Medica, A.O.U. Federico II, 80131 Naples, Italy"},{"name":"Department of Molecular Medicine and Medical Biotechnology, University Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9111-2985","authenticated-orcid":false,"given":"Daniele","family":"De Brasi","sequence":"additional","affiliation":[{"name":"U.O.C. Pediatria, AORN Santobono Pausilipon, 80129 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Della Monica","sequence":"additional","affiliation":[{"name":"Medical and Laboratory Genetic Unit, Antonio Cardarelli Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Cesario","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Bambino Ges\u00f9 Children Hospital IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Petrocchi","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Bambino Ges\u00f9 Children Hospital IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9037-4297","authenticated-orcid":false,"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Bambino Ges\u00f9 Children Hospital IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"D\u2019Alterio","sequence":"additional","affiliation":[{"name":"European School of Molecular Medicine, Universit\u00e0 Degli Studi di Milano, 20139 Milan, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9558-0356","authenticated-orcid":false,"given":"Achille","family":"Iolascon","sequence":"additional","affiliation":[{"name":"U.O.C. Genetica Medica, A.O.U. Federico II, 80131 Naples, Italy"},{"name":"Department of Molecular Medicine and Medical Biotechnology, University Federico II, 80131 Naples, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3306-1259","authenticated-orcid":false,"given":"Mario","family":"Capasso","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University Federico II, 80131 Naples, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Piscopo","sequence":"additional","affiliation":[{"name":"Medical and Laboratory Genetic Unit, Antonio Cardarelli Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/cge.12499","article-title":"Cornelia de Lange Syndrome","volume":"88","author":"Boyle","year":"2015","journal-title":"Clin. 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