{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:12:09Z","timestamp":1790813529054,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzen Municipality","doi-asserted-by":"publisher","award":["SZSM202311028"],"award-info":[{"award-number":["SZSM202311028"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Approximately 7% of individuals with dystrophinopathy remain undiagnosed at the genetic level using conventional genetic tests like multiplex ligation\u2010dependent probe amplification (MLPA) and next\u2010generation sequencing (NGS). We used the optical genome mapping (OGM) technology to detect and analyze uncommon mutations or structural variations (SVs) within the <jats:italic>DMD<\/jats:italic> gene, thus contributing to more precise clinical diagnoses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We herein included eight patients with dystrophinopathy (six males and two females) in whom pathogenic variants of the <jats:italic>DMD<\/jats:italic> gene could not be accurately identified using MLPA and NGS. Clinical data were collected for all patients and genetic testing was performed using OGM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Conventional methods (MLPA and NGS) failed to detect pathogenic mutations in six out of eight individuals (four males and two females). OGM testing uncovered rare mutations in the <jats:italic>DMD<\/jats:italic> gene in four patients, including a pericentric inversion in chromosome X (one male), a complex rearrangement (one male), and two X\u2013autosome translocations (two females). No mutations were detected in the remaining two male patients. OGM also accurately mapped balanced X\u2013autosome translocations in female patients, defining chromosomal breakpoints. In the other two male patients in whom MLPA suggested non\u2010contiguous exon\u00a0duplications or deletions in the <jats:italic>DMD<\/jats:italic> gene, OGM characterized one case as a complex rearrangement and the other as a deletion within the <jats:italic>DMD<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>OGM is a valuable diagnostic tool for dystrophinopathy patients with negative results from conventional genetic tests. It can effectively elucidate complex SVs and pinpoint breakpoints in X\u2013autosomal translocations in female patients, facilitating prompt and appropriate interventions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.52245","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T10:44:56Z","timestamp":1732272296000},"page":"43-55","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Optical genome mapping: Unraveling complex variations and enabling precise diagnosis in dystrophinopathy"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1734-8316","authenticated-orcid":false,"given":"Jiahui","family":"Mai","sequence":"first","affiliation":[{"name":"Department of Neurology Shenzhen Children's Hospital of China Medical University  No. 7019 Yitian Road, Futian District Shenzhen 518038 Guangdong PR 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