{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T15:02:15Z","timestamp":1785078135327,"version":"3.55.0"},"reference-count":33,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Duchenne muscular dystrophy (DMD) is an X\u2010linked neuromuscular disorder caused by pathogenic variants in the\n                      <jats:italic>DMD<\/jats:italic>\n                      gene, which encodes dystrophin, a cytoskeletal protein linking intracellular actin to the extracellular matrix via the dystrophin\u2010associated protein complex and maintaining muscle fiber integrity. With the emergence of disease\u2010modifying therapies, early and accurate molecular diagnosis is increasingly important. Whole\u2010exome sequencing (WES) is widely used to evaluate unexplained hyperCKemia and distinguish DMD from other inherited neuromuscular disorders.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      WES identified a novel hemizygous frameshift variant in\n                      <jats:italic>DMD<\/jats:italic>\n                      (NM_004006.3:c.6050_6051del; p.Leu2017Profs*5) in a Taiwanese boy with markedly elevated creatine kinase levels (&gt;\u200910,000\u2009U\/L) and clinical features consistent with DMD. The variant was classified as likely pathogenic according to ACMG criteria (PVS1, PS2, PP3). Comparative genomic analysis demonstrated strong evolutionary conservation at the variant site within the 16th spectrin\u2010like repeat (exon 42), with phastCons scores of 1 and phyloP scores of +2.925 and +1.015. AlphaFold\u2010based structural modeling suggested disruption of the three\u2010helix bundle architecture, while CHARMM\u2010based energy analysis suggested a potential destabilizing effect that appeared more consistent with previously reported pathogenic exon 42 frameshift variants than with benign missense variants at the same locus.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This is the first reported case of DMD associated with the novel frameshift variant c.6050_6051del (p.Leu2017Profs*5). Integrated genomic, evolutionary, and structural analyses support the likely pathogenic interpretation of this variant. This study expands the mutational spectrum of DMD and highlights the value of combining WES with structure\u2010informed approaches for variant interpretation. These findings provide preliminary structural insights into the potential effects of the identified variant and highlight the possible utility of structure\u2010informed variant interpretation in the absence of functional assays.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70257","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:17:36Z","timestamp":1782965856000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel\n                    <i>DMD<\/i>\n                    Frameshift Variant (p.Leu2017Profs*5) in Spectrin\u2010Like Repeat 16 Expands the Mutational Spectrum of DMD"],"prefix":"10.1002","volume":"14","author":[{"given":"Yu\u2010Chin","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Tri\u2010Service General Hospital National Defense Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. W. Gant","family":"Luxton","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology University of California  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwei\u2010Jen","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry National Defense Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9258-188X","authenticated-orcid":false,"given":"Yu\u2010Yang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tri\u2010Service General Hospital National Defense Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung\u2010Chi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology Yuanpei University of Medical Technology  Hsinchu Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo\u2010Sheng","family":"Hung","sequence":"additional","affiliation":[{"name":"Center for Precision Medicine and Genomics, Tri\u2010Service General Hospital National Defense Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Tsong","family":"Lai","sequence":"additional","affiliation":[{"name":"KimForest Enterprise Co., Ltd.  New Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9208-0890","authenticated-orcid":false,"given":"Chih\u2010Fen","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tri\u2010Service General Hospital National Defense Medical University  Taipei Taiwan"},{"name":"Department of Pediatrics, School of Medicine, College of Medicine National Defense Medical University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103387"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20586"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887-025-05756-9"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00787-019-01298-5"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0508-z"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30025-5"},{"key":"e_1_2_10_8_1","volume-title":"GeneReviews","author":"Darras B. 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