{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:09:33Z","timestamp":1790813373345,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["444748124"],"award-info":[{"award-number":["444748124"]}],"id":[{"id":"10.13039\/501100001659","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":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Dystrophinopathies caused by variants in the <jats:italic>DMD<\/jats:italic> gene are a well\u2010studied muscle disease. The most common type of variant in <jats:italic>DMD<\/jats:italic> are large deletions. Very rarely reported forms of variants are chromosomal translocations, inversions and deep intronic variants (DIVs) because they are not detectable by standard diagnostic techniques (sequencing of coding sequence, copy number variant detection). This might be the reason that some clinically and histologically proven dystrophinopathy cases remain unsolved.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used whole genome sequencing (WGS) to screen the entire <jats:italic>DMD<\/jats:italic> gene for variants in one of two brothers suffering from typical muscular dystrophy with strongly elevated creatine kinase levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Although a pathogenic DIV could not be detected, we were able to identify a pericentric inversion with breakpoints in <jats:italic>DMD<\/jats:italic> intron 44 and Xq13.3, which could be confirmed by Sanger sequencing in the index as well as in his brother and mother. As this variation affects a major part of <jats:italic>DMD<\/jats:italic> it is most likely disease causing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings elucidate that WGS is capable of detecting large structural rearrangements and might be suitable for the genetic diagnostics of dystrophinopathies in the future. In particular, inversions might be a more frequent cause for dystrophinopathies as anticipated and should be considered in genetically unsolved dystrophinopathy cases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2028","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T09:04:58Z","timestamp":1659344698000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Detection of pericentric inversion with breakpoint in <i>DMD<\/i> by whole genome sequencing"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3100-1415","authenticated-orcid":false,"given":"Ann\u2010Kathrin","family":"Zaum","sequence":"first","affiliation":[{"name":"Department of Human Genetics University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indrajit","family":"Nanda","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfram","family":"Kress","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Rost","sequence":"additional","affiliation":[{"name":"Department of Human Genetics University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103387"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20586"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.108"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000087531"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30617"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.122.4.809"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.101"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198805263182104"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22353"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.45.27305"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90504-6"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20806"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(88)90113-9"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24191"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2016.7"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-009-0679-9"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.150.5.1209"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1086\/342208"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105778"},{"issue":"6","key":"e_1_2_9_22_1","first-page":"1231","article-title":"Molecular analysis of recombination in a family with Duchenne muscular dystrophy and a large pericentric X chromosome inversion","volume":"58","author":"Shashi V.","year":"1996","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_9_23_1","volume-title":"RepeatMasker Open\u20104.0","author":"Smit A."},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2012.131"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2017.12.037"},{"key":"e_1_2_9_26_1","volume-title":"Erweiterte Diagnostik bei neuromuskul\u00e4ren Erkrankungen: vom Genpanel zum Whole Genome Sequencing","author":"Zaum A.\u2010K.","year":"2019"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1098"}],"container-title":["Molecular Genetics &amp; 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