{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T14:28:13Z","timestamp":1776954493137,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Distal myopathies are a group of rare muscle disorders characterized by selective or predominant weakness in the feet and\/or hands. In 2019, <jats:italic>ACTN2<\/jats:italic>\u00a0gene was firstly identified to be a cause of a new adult\u2010onset distal muscular dystrophy calling actininopathy and another distinctly different myopathy, named multiple structured core disease (MsCD). Thus, the various phenotypes and limited mutations in ACTN2\u2010related myopathy make the genotype\u2010phenotype correlation hard to understand.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To investigate the clinical features and histological findings in a Chinese family with distal myopathy. Whole exome sequencing and several functional studies were performed to explore the pathogenesis of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We firstly identified a novel frameshift variant (c.2504delT, p.Phe835Serfs*66) within <jats:italic>ACTN2<\/jats:italic> in a family including three patients. The patients exhibited adult\u2010onset distal myopathy with multi\u2010minicores, which, interestingly, was more like a combination of MsCD and actininopathy. Moreover, functional analysis using muscle samples revealed that the variant significantly increased the expression level of \u03b1\u2010actinin\u20102 and resulted in abnormal Z\u2010line organization of muscle fiber. Vitro studies suggested aggregate formations might be involved in the pathogenesis of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results expanded the phenotypes of ACTN2\u2010related myopathy and provided helpful information to clarify the molecular mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13697","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T10:40:30Z","timestamp":1624617630000},"page":"1198-1205","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A novel frameshift <i>ACTN2<\/i> variant causes a rare adult\u2010onset distal myopathy with multi\u2010minicores"],"prefix":"10.1111","volume":"27","author":[{"given":"Lei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of Medicine Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dian\u2010Fu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of Medicine Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai\u2010Lin","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of Medicine Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gong\u2010Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, 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