{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:14:39Z","timestamp":1790723679102,"version":"4.1.0"},"reference-count":21,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI22\/01127"],"award-info":[{"award-number":["PI22\/01127"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI22\/00272"],"award-info":[{"award-number":["PI22\/00272"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rare diseases (RDs) often have a genetic basis, yet conventional diagnostic techniques fail to identify causative genetic variations in up to 50% of cases. Structural variants (SVs), including balanced rearrangements, frequently evade detection by karyotyping, microarray, and exome sequencing. The present study utilized optical genome mapping (OGM) to investigate two patients with RDs whose genetic etiology remained unresolved despite prior genomic analyses. Patient 1 exhibited a balanced reciprocal translocation disrupting the BCL11A gene, associated with Dias-Logan syndrome. Patient 2 had a mosaic 682 kb deletion near the IHH gene, causing ectopic enhancer\u2013promoter interactions and polydactyly, mirroring phenotypes observed in mouse models and similar human cases. These findings highlight OGM\u2019s efficacy in identifying complex SVs and underline novel pathogenic mechanisms in rare genetic disorders. Consequently, the incorporation of OGM into routine diagnostic procedures will enhance genetic diagnosis, discover new syndromes of currently unknown cause, and eventually improve the clinical management of numerous patients with rare diseases.<\/jats:p>","DOI":"10.3390\/ijms26031244","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T05:08:26Z","timestamp":1738300106000},"page":"1244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Utility of Optical Genome Mapping for Accurate Detection and Fine-Mapping of Structural Variants in Elusive Rare Diseases"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4271-5859","authenticated-orcid":false,"given":"Carmen","family":"Orellana","sequence":"first","affiliation":[{"name":"Genetics Unit, Hospital Universitario y Polit\u00e9cnico La Fe, 46026 Valencia, Spain"},{"name":"Traslational Genetics Research Group, Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9234-2953","authenticated-orcid":false,"given":"Monica","family":"Rosello","sequence":"additional","affiliation":[{"name":"Genetics Unit, Hospital Universitario y Polit\u00e9cnico La Fe, 46026 Valencia, Spain"},{"name":"Traslational Genetics Research Group, Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amparo","family":"Sanchis","sequence":"additional","affiliation":[{"name":"Pediatrics Service, Hospital Universitario Doctor Peset, 46017 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3031-6124","authenticated-orcid":false,"given":"Laia","family":"Pedrola","sequence":"additional","affiliation":[{"name":"Genetics Unit, Hospital 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Leonor","family":"Senent","sequence":"additional","affiliation":[{"name":"Hematology and Hemotherapy Service, Hospital Universitario y Polit\u00e9cnico La Fe, 46026 Valencia, Spain"},{"name":"Hematology Research Group, Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en C\u00e1ncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esperanza","family":"Such","sequence":"additional","affiliation":[{"name":"Hematology and Hemotherapy Service, Hospital Universitario y Polit\u00e9cnico La Fe, 46026 Valencia, Spain"},{"name":"Hematology Research Group, Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en C\u00e1ncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, 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