{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:30:20Z","timestamp":1768523420821,"version":"3.49.0"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cornelia de Lange syndrome (CdLS) is a rare genetic disorder characterized by congenital multiple anomalies, developmental delay, and distinctive facial features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed chromosomal microarray analysis (CMA), whole exome sequencing (WES), linked\u2010read whole\u2010genome sequencing (WGS) and optical genome mapping (OGM) to investigate an undiagnosed case of CdLS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A male patient presented clinical features consistent with CdLS, including a short nose, synophrys, small hands, hearing impairment, refractory complex partial seizures, and developmental delay. Amniocentesis at 28 gestational weeks and karyotyping revealed a presumably balanced translocation between chromosome 5 and chromosome 6. CMA and WES failed to identify copy number variants or a molecular diagnosis. Further analysis using WGS and OGM identified two translocation events on chromosome 5, resulting in three derivative chromosomes: 46,XY, der(2)t(2;5)(q32.3;p13.2),der(5)t(5;6)(p13.1;q12),der(6)t(2;6)(q32.3;q12)ins(6;5)(q12;p13.1p13.2). These rearrangements disrupted the <jats:italic>NIPBL<\/jats:italic> gene, a key gene with CdLS, splitting it across derivative chromosomes 2 and 6. Phasing studies revealed that these translocations originated from the paternal lineage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This case highlights the intricate genetic underpinnings of CdLS in this patient and underscores the diagnostic value of high\u2010resolution genomic analyses in elucidating complex chromosomal rearrangements.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70115","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T09:34:21Z","timestamp":1750152861000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of De Novo Chromosomal Translocations Disrupting <scp><i>NIPBL<\/i><\/scp> in a Patient With Cornelia de Lange Syndrome by Full Genome Analysis"],"prefix":"10.1002","volume":"13","author":[{"given":"Hsiao\u2010Jung","family":"Kao","sequence":"first","affiliation":[{"name":"Division of Cardiovascular and Metabolic Diseases Institute of Biomedical Sciences, Academia Sinica  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elin H. F.","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular and Metabolic Diseases Institute of Biomedical Sciences, Academia Sinica  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erh\u2010Chan","family":"Yeh","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular and Metabolic Diseases Institute of Biomedical Sciences, Academia Sinica  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiao\u2010Huei","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular and Metabolic Diseases Institute of Biomedical Sciences, Academia Sinica  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng\u2010Jen","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular and Metabolic Diseases Institute of Biomedical Sciences, Academia Sinica  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsang\u2010Ming","family":"Ko","sequence":"additional","affiliation":[{"name":"Genephile Bioscience Laboratory  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wuh\u2010Liang","family":"Hwu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics National Taiwan University Hospital  Taipei Taiwan"},{"name":"Department of Pediatrics National Taiwan University Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pui\u2010Yan","family":"Kwok","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular and Metabolic Diseases Institute of Biomedical Sciences, Academia Sinica  Taipei Taiwan"},{"name":"Cardiovascular Research Institute, Institute for Human Genetics, and Department of Dermatology University of California, San Francisco  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5011-7499","authenticated-orcid":false,"given":"Ni\u2010Chung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics National Taiwan University Hospital  Taipei Taiwan"},{"name":"Department of Pediatrics National Taiwan University Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,17]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2024.1358334"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13050740"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24384"},{"key":"e_1_2_13_5_1","volume-title":"GeneReviews","author":"Deardorff M. 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