{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T06:57:39Z","timestamp":1775977059452,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T00:00:00Z","timestamp":1721088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:p>Dystrophinopathy is caused by alterations in the dystrophin gene. The severe phenotype, Duchenne muscular dystrophy (DMD), is caused by a lack of dystrophin in skeletal muscles, resulting in necrosis and regenerating fibers, inflammatory cells, and muscle fibrosis. Progressive muscle weakness is a characteristic finding of this condition. Here, we encountered a rare case of a 10\u2010year\u2010old patient with asymptomatic dystrophinopathy with no dystrophin expression and investigated the reason for the absence of muscle weakness to obtain therapeutic insights for DMD. Using RNA\u2010seq analysis, gene expression in skeletal muscles was compared among patients with asymptomatic dystrophinopathy, three patients with typical DMD, and two patients without dystrophinopathy who were leading normal daily lives. Cathepsin K (<jats:italic>CTSK<\/jats:italic>), myosin heavy chain 3 (<jats:italic>MYH3<\/jats:italic>), and nodal modulator 3\u2010like genes exhibited a\u2009&gt;8\u2010fold change, whereas crystallin mu gene (<jats:italic>CRYM<\/jats:italic>) showed a\u2009&lt;1\/8\u2010fold change in patients with typical DMD compared with their expression in the patient with asymptomatic dystrophinopathy. Additionally, <jats:italic>CTSK<\/jats:italic> and <jats:italic>MYH3<\/jats:italic> expression exhibited a\u2009&gt;16\u2010fold change (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01), whereas <jats:italic>CRYM<\/jats:italic> expression showed a\u2009&lt;1\/16\u2010fold change (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01) in patients with typical DMD compared with their expression in those without dystrophinopathy. <jats:italic>CTSK<\/jats:italic> plays an essential role in skeletal muscle loss, fibrosis, and inflammation in response to muscles injected with cardiotoxin, one of the most common reagents that induce muscle injury. Increased <jats:italic>CTSK<\/jats:italic> expression is associated with muscle injury or necrosis in patients with DMD. The lack of muscle weakness in the patient with asymptomatic dystrophinopathy might be attributed to the low <jats:italic>CTSK<\/jats:italic> expression in the muscles. To the best of our knowledge, this is the first report to demonstrate that <jats:italic>CTSK<\/jats:italic> expression was significantly higher in the skeletal muscles of patients with DMD with a typical phenotype than in those without dystrophinopathy.<\/jats:p>","DOI":"10.1111\/neup.12995","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T05:18:35Z","timestamp":1721193515000},"page":"411-421","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Increase in cathepsin K gene expression in <scp>Duchenne<\/scp> muscular dystrophy skeletal muscle"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2161-8497","authenticated-orcid":false,"given":"Shigemi","family":"Kimura","sequence":"first","affiliation":[{"name":"Department of Pediatrics Kumamoto Takumadai Rehabilitation Hospital  Kumamoto Japan"},{"name":"Data Science Center for Medicine and Hospital Management Toyama University Hospital  Toyama Japan"},{"name":"Department of Medical Systems Kobe University Graduate School of Medicine  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriko","family":"Miyake","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Research Institute, National Center for Global Health and Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiro","family":"Ozasa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kumamoto University Hospital  Kumamoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroe","family":"Ueno","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kumamoto Takumadai Rehabilitation Hospital  Kumamoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinobu","family":"Ohtani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kumamoto Takumadai Rehabilitation Hospital  Kumamoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7568-8135","authenticated-orcid":false,"given":"Yutaka","family":"Takaoka","sequence":"additional","affiliation":[{"name":"Data Science Center for Medicine and Hospital Management Toyama University Hospital  Toyama Japan"},{"name":"Department of Medical Systems Kobe University Graduate School of Medicine  Kobe Japan"},{"name":"Faculty of Health Sciences Kobe Tokiwa University  Kobe Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9452-112X","authenticated-orcid":false,"given":"Ichizo","family":"Nishino","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Research National Institute of Neuroscience, National Center of Neurology and Psychiatry  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0098-2997(91)90001-3"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-022-02485-2"},{"key":"e_1_2_9_4_1","first-page":"498","article-title":"The molecular basis for Duchenne versus Becker muscular dystrophy: Correlation of severity with type of deletion","volume":"45","author":"Koenig M","year":"1989","journal-title":"Am J Hum Genet"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00343141"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/333861a0"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2014.02.006"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2019.09.009"},{"key":"e_1_2_9_9_1","first-page":"572","article-title":"Outside in: The matrix as a modifier of muscular dystrophy","volume":"2017","author":"Quattrocelli M","year":"1864","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318207afeb"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006019"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.049"},{"key":"e_1_2_9_13_1","unstructured":"List of variants in gene DMD reported as likely benign for Duchenne muscular dystrophy \u2013 ClinVar Miner (utah.edu) Accessed from:https:\/\/clinvarminer.genetics.utah.edu\/variants\u2010by\u2010gene\/DMD\/condition\/Duchenne%20muscular%20dystrophy\/likely%20benign. 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