{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:19:42Z","timestamp":1792804782228,"version":"4.5.0"},"reference-count":19,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T00:00:00Z","timestamp":1709769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MGZ\u2014Medizinisch Genetisches Zentrum, Munich, Germany","id":[{"id":"https:\/\/ror.org\/027nwsc63","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Chromosome analysis (CA) and chromosomal microarray analysis (CMA) have been successfully used to diagnose genetic disorders. However, many conditions remain undiagnosed due to limitations in resolution (CA) and detection of only unbalanced events (CMA). Optical genome mapping (OGM) has the potential to address these limitations by capturing both structural variants (SVs) resulting in copy number changes and balanced rearrangements with high resolution. In this study, we investigated OGM\u2019s concordance using 87 SVs previously identified by CA, CMA, or Southern blot. Overall, OGM was 98% concordant with only three discordant cases: (1) uncalled translocation with one breakpoint in a centromere; (2) uncalled duplication with breakpoints in the pseudoautosomal region 1; and (3) uncalled mosaic triplication originating from a marker chromosome. OGM provided diagnosis for three previously unsolved cases: (1) disruption of the SON gene due to a balanced reciprocal translocation; (2) disruption of the NBEA gene due to an inverted insertion; (3) disruption of the TSC2 gene due to a mosaic deletion. We show that OGM is a valid method for the detection of many types of SVs in a single assay and is highly concordant with legacy cytogenomic methods; however, it has limited SV detection capabilities in centromeric and pseudoautosomal regions.<\/jats:p>","DOI":"10.3390\/genes15030342","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T04:19:02Z","timestamp":1709785142000},"page":"342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Optical Genome Mapping as a Potential Routine Clinical Diagnostic Method"],"prefix":"10.3390","volume":"15","author":[{"given":"Hayk","family":"Barseghyan","sequence":"first","affiliation":[{"name":"Medical Genetics Center (MGZ), 80335 Munich, Germany"},{"name":"Center for Genetic Medicine Research, Children\u2019s National Research Institute, Children\u2019s National Hospital, Washington, DC 20012, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Eisenreich","sequence":"additional","affiliation":[{"name":"Medical Genetics Center (MGZ), 80335 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgenia","family":"Lindt","sequence":"additional","affiliation":[{"name":"Medical Genetics Center (MGZ), 80335 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Wendlandt","sequence":"additional","affiliation":[{"name":"Institute of Medical Biochemistry and Molecular Biology, University Medicine of Greifswald, 17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florentine","family":"Scharf","sequence":"additional","affiliation":[{"name":"Medical Genetics Center (MGZ), 80335 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Benet-Pages","sequence":"additional","affiliation":[{"name":"Medical Genetics Center (MGZ), 80335 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Sendelbach","sequence":"additional","affiliation":[{"name":"Medical Genetics Center (MGZ), 80335 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Neuhann","sequence":"additional","affiliation":[{"name":"Medical Genetics Center (MGZ), 80335 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Abicht","sequence":"additional","affiliation":[{"name":"Medical Genetics Center (MGZ), 80335 Munich, Germany"},{"name":"Friedrich-Baur-Institute, Department of Neurology, Klinikum der Universit\u00e4t, Ludwig-Maximilians-Universit\u00e4t, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5172-2818","authenticated-orcid":false,"given":"Elke","family":"Holinski-Feder","sequence":"additional","affiliation":[{"name":"Medical Genetics Center (MGZ), 80335 Munich, Germany"},{"name":"Department of Medicine IV, Klinikum der Universit\u00e4t, Ludwig-Maximilians-Universit\u00e4t, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo","family":"Koehler","sequence":"additional","affiliation":[{"name":"Medical Genetics Center (MGZ), 80335 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"D789","DOI":"10.1093\/nar\/gku1205","article-title":"OMIM.org: Online Mendelian Inheritance in Man (OMIM\u00ae), an online catalog of human genes and genetic disorders","volume":"43","author":"Amberger","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1038\/s41436-018-0040-6","article-title":"Yield of additional genetic testing after chromosomal microarray for diagnosis of neurodevelopmental disability and congenital anomalies: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)","volume":"20","author":"Waggoner","year":"2018","journal-title":"Genet. 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