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Short\u2010read whole genome sequencing was performed on 195 individuals from 105 families, 108 of whom were affected. 100\/108 of the affected individuals had prior relevant genetic testing, with no pathogenic variant being identified. The study group comprised 42 trios in which both parental samples were available for testing (42 affected individuals and 126 unaffected parents), 61 singletons (unrelated affected individuals), and two families with more than one affected individual. The results showed that 32 unrelated probands from 105 families (30.5%) had likely causative coding region\u2010disrupting variants. Four loci were identified in &gt;\u20091 proband:\n                    <jats:italic>NIPBL<\/jats:italic>\n                    (10),\n                    <jats:italic>ANKRD11<\/jats:italic>\n                    (6),\n                    <jats:italic>EP300<\/jats:italic>\n                    (3), and\n                    <jats:italic>EHMT1<\/jats:italic>\n                    (2). Single variants were detected in the remaining genes (\n                    <jats:italic>EBF3<\/jats:italic>\n                    ,\n                    <jats:italic>KMT2A<\/jats:italic>\n                    ,\n                    <jats:italic>MED13L<\/jats:italic>\n                    ,\n                    <jats:italic>NLGN3<\/jats:italic>\n                    ,\n                    <jats:italic>NR2F1<\/jats:italic>\n                    ,\n                    <jats:italic>PHIP<\/jats:italic>\n                    ,\n                    <jats:italic>PUF60<\/jats:italic>\n                    ,\n                    <jats:italic>SET<\/jats:italic>\n                    ,\n                    <jats:italic>SETD5<\/jats:italic>\n                    ,\n                    <jats:italic>SMC1A<\/jats:italic>\n                    , and\n                    <jats:italic>TBL1XR1<\/jats:italic>\n                    ). Possibly causative variants in noncoding regions of\n                    <jats:italic>NIPBL<\/jats:italic>\n                    were identified in four individuals. Single de novo variants were identified in five genes not previously reported to be associated with any developmental disorder:\n                    <jats:italic>ARID3A<\/jats:italic>\n                    ,\n                    <jats:italic>PIK3C3<\/jats:italic>\n                    ,\n                    <jats:italic>MCM7<\/jats:italic>\n                    ,\n                    <jats:italic>MIS18BP1<\/jats:italic>\n                    , and\n                    <jats:italic>WDR18<\/jats:italic>\n                    . The clustering of de novo noncoding variants implicates a single upstream open reading frame (uORF) and a small region in Intron 21 in\n                    <jats:italic>NIPBL<\/jats:italic>\n                    regulation. Causative variants in genes encoding chromatin\u2010associated proteins, with no defined influence on cohesin function, appear to result in CdLS\u2010like clinical features. This study demonstrates the clinical utility of whole genome sequencing as a diagnostic test in individuals presenting with CdLS or CdLS\u2010like phenotypes.\n                  <\/jats:p>","DOI":"10.1155\/humu\/4711663","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T08:18:51Z","timestamp":1738225131000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Whole Genome Sequencing of \u201cMutation\u2010Negative\u201d Individuals With Cornelia de Lange Syndrome"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8905-5379","authenticated-orcid":false,"given":"Morad","family":"Ansari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihail","family":"Halachev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Parry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L.","family":"Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elston N.","family":"D\u2019Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Barnett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2972-5481","authenticated-orcid":false,"given":"Andrew O. 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