{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:49:44Z","timestamp":1789069784296,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["U01HG007672"],"award-info":[{"award-number":["U01HG007672"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Currently available structural variant (SV) detection methods do not span the complete spectrum of disease\u2010causing SVs. Optical genome mapping (OGM), an emerging technology with the potential to resolve diagnostic dilemmas, was performed to investigate clinically\u2010relevant SVs in a 4\u2010year\u2010old male with an epileptic encephalopathy of undiagnosed molecular origin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>OGM was utilized to image long, megabase\u2010size DNA molecules, fluorescently labeled at specific sequence motifs throughout the genome with high sensitivity for detection of SVs greater than 500\u00a0bp in size. OGM results were confirmed in a CLIA\u2010certified laboratory via mate\u2010pair sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>OGM identified a mosaic, <jats:italic>de novo<\/jats:italic> 90\u00a0kb deletion and inversion on the X chromosome disrupting the <jats:italic>CDKL5<\/jats:italic> gene. Detection of the mosaic deletion, which had been previously undetected by chromosomal microarray, an infantile epilepsy panel including exon\u2010level microarray for <jats:italic>CDKL5<\/jats:italic>, exome sequencing as well as genome sequencing, resulted in a diagnosis of X\u2010linked dominant early infantile epileptic encephalopathy\u20102.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>OGM affords an effective technology for the detection of SVs, especially those that are mosaic, since these remain difficult to detect with current NGS technologies and with conventional chromosomal microarrays. Further research in undiagnosed populations with OGM is warranted.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1665","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T05:15:22Z","timestamp":1620364522000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Detection of a mosaic <i>CDKL5<\/i> deletion and inversion by optical genome mapping ends an exhaustive diagnostic odyssey"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0586-9277","authenticated-orcid":false,"given":"Heidi","family":"Cope","sequence":"first","affiliation":[{"name":"Division of Medical Genetics Department of Pediatrics Duke University Medical Center Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayk","family":"Barseghyan","sequence":"additional","affiliation":[{"name":"Center for Genetic Medicine Research Children\u2019s National Hospital 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