{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:32:37Z","timestamp":1780407157187,"version":"3.54.1"},"reference-count":13,"publisher":"Cold Spring Harbor Laboratory","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:p>Mosaicism in Cornelia de Lange syndrome (CdLS) has been reported in clinically diagnosed CdLS patients with negative molecular testing using blood as the specimen, particularly in the <jats:italic>NIPBL<\/jats:italic> gene. Here we report a novel mosaic variant in <jats:italic>SMC1A<\/jats:italic> identified in the buccal swab DNA of a patient with a mild CdLS phenotype. Our patient presented with global developmental delay, dysmorphic features, microcephaly, and short stature, with no limb defect. Face2Gene, a digital tool that analyzes facial morphology, demonstrated a 97% match between our patient and the CdLS gestalt. An initial next-generation sequencing (NGS)-based CdLS panel test, including <jats:italic>NIPBL<\/jats:italic>, <jats:italic>HDAC8<\/jats:italic>, <jats:italic>RAD21<\/jats:italic>, <jats:italic>SMC1A<\/jats:italic>, and <jats:italic>SMC3<\/jats:italic>, completed using DNA isolated from leukocytes, was negative, and subsequent trio exome sequencing was nondiagnostic. The exome identified biallelic variants of uncertain significance in a candidate gene, <jats:italic>NSMCE2<\/jats:italic>. In the pursuit of a molecular diagnosis, a second NGS-based CdLS panel test was ordered on a buccal swab specimen and a novel variant, c.793_795delGAG (p.Glu265del) in <jats:italic>SMC1A<\/jats:italic>, was detected at 60% mosaicism. Retrospective analysis of the former panel and exome data revealed the <jats:italic>SMC1A<\/jats:italic> variant at 4% and 2%, respectively, both far below standard reporting thresholds. Given that mosaicism has been frequently reported in CdLS, we suggest selecting a different tissue for testing in clinically suspected CdLS cases, even after negative molecular results via blood specimen.<\/jats:p>","DOI":"10.1101\/mcs.a005322","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T23:07:54Z","timestamp":1592003274000},"page":"a005322","source":"Crossref","is-referenced-by-count":8,"title":["A novel mosaic variant on <i>SMC1A<\/i> reported in buccal mucosa cells, albeit not in blood, of a patient with Cornelia de Lange\u2013like presentation"],"prefix":"10.1101","volume":"6","author":[{"given":"Aixa","family":"Gonzalez Garcia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Malone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2020,6,12]]},"reference":[{"key":"2021112406082038000_6.3.a005322.1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102573"},{"key":"2021112406082038000_6.3.a005322.2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2010.01408.x"},{"key":"2021112406082038000_6.3.a005322.3","doi-asserted-by":"publisher","DOI":"10.1086\/511888"},{"key":"2021112406082038000_6.3.a005322.4","doi-asserted-by":"publisher","DOI":"10.4274\/jcrpe.4349"},{"key":"2021112406082038000_6.3.a005322.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2012.12.009"},{"key":"2021112406082038000_6.3.a005322.6","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1105"},{"key":"2021112406082038000_6.3.a005322.7","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00203"},{"key":"2021112406082038000_6.3.a005322.8","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21031042"},{"key":"2021112406082038000_6.3.a005322.9","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"2021112406082038000_6.3.a005322.10","doi-asserted-by":"publisher","DOI":"10.1172\/JCI73264"},{"key":"2021112406082038000_6.3.a005322.11","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601218"},{"key":"2021112406082038000_6.3.a005322.12","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35381"},{"key":"2021112406082038000_6.3.a005322.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-25311-0"}],"container-title":["Molecular Case Studies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/mcs.a005322","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T14:13:39Z","timestamp":1637763219000},"score":1,"resource":{"primary":{"URL":"http:\/\/molecularcasestudies.cshlp.org\/lookup\/doi\/10.1101\/mcs.a005322"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6]]},"references-count":13,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,6,12]]},"published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1101\/mcs.a005322"],"URL":"https:\/\/doi.org\/10.1101\/mcs.a005322","relation":{},"ISSN":["2373-2865","2373-2873"],"issn-type":[{"value":"2373-2865","type":"print"},{"value":"2373-2873","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6]]}}}