{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:47:50Z","timestamp":1791272870387,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,1,21]],"date-time":"2014-01-21T00:00:00Z","timestamp":1390262400000},"content-version":"vor","delay-in-days":51,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"NIH National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["NS048843"],"award-info":[{"award-number":["NS048843"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["AR049077"],"award-info":[{"award-number":["AR049077"]}]},{"name":"NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["AR48143"],"award-info":[{"award-number":["AR48143"]}]},{"name":"NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["AR055947"],"award-info":[{"award-number":["AR055947"]}]},{"name":"NIH","award":["UL1RR024160-06S4"],"award-info":[{"award-number":["UL1RR024160-06S4"]}]},{"name":"NIH","award":["K08NS064293"],"award-info":[{"award-number":["K08NS064293"]}]},{"name":"University of Rochester Clinical and Translational Science Institute\/Clinical Research Center","award":["NIH\/NCATS\/NCRR, UL1RR024160"],"award-info":[{"award-number":["NIH\/NCATS\/NCRR, UL1RR024160"]}]},{"name":"Saunders Family Fund, Run America, Muscular Dystrophy Association"},{"DOI":"10.13039\/100007451","name":"Cell Science Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007451","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To develop RNA splicing biomarkers of disease severity and therapeutic response in myotonic dystrophy type 1 (DM1) and type 2 (DM2).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a discovery cohort, we used microarrays to perform global analysis of alternative splicing in DM1 and DM2. The newly identified splicing changes were combined with previous data to create a panel of 50 putative splicing defects. In a validation cohort of 50 DM1 subjects, we measured the strength of ankle dorsiflexion (ADF) and then obtained a needle biopsy of tibialis anterior (TA) to analyze splice events in muscle RNA. The specificity of DM\u2010associated splicing defects was assessed in disease controls. The CTG expansion size in muscle tissue was determined by Southern blot. The reversibility of splicing defects was assessed in transgenic mice by using antisense oligonucleotides to reduce levels of toxic RNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Forty\u2010two splicing defects were confirmed in TA muscle in the validation cohort. Among these, 20 events showed graded changes that correlated with ADF weakness. Five other splice events were strongly affected in DM1 subjects with normal ADF strength. Comparison to disease controls and mouse models indicated that splicing changes were DM\u2010specific, mainly attributable to MBNL1 sequestration, and reversible in mice by targeted knockdown of toxic RNA. Splicing defects and weakness were not correlated with CTG expansion size in muscle tissue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Alternative splicing changes in skeletal muscle may serve as biomarkers of disease severity and therapeutic response in myotonic dystrophy. Ann Neurol 2013;74:862\u2013872<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.23992","type":"journal-article","created":{"date-parts":[[2013,8,8]],"date-time":"2013-08-08T11:20:47Z","timestamp":1375960847000},"page":"862-872","source":"Crossref","is-referenced-by-count":273,"title":["Splicing biomarkers of disease severity in myotonic dystrophy"],"prefix":"10.1002","volume":"74","author":[{"given":"Masayuki","family":"Nakamori","sequence":"first","affiliation":[{"name":"Department of Neurology University of Rochester Medical Center Rochester NY"},{"name":"Center for Neural Development and Disease University of Rochester Medical Center Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Sobczak","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Rochester Medical Center Rochester NY"},{"name":"Center for Neural Development and Disease University of Rochester Medical Center Rochester 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Disease University of Rochester Medical Center Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice S.","family":"Swanson","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology University of Florida, College of Medicine Gainesville FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Richard T.","family":"Moxley","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Rochester Medical Center Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"Thornton","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Rochester Medical Center Rochester NY"},{"name":"Center for Neural Development and Disease University of Rochester Medical Center Rochester NY"},{"name":"Center for RNA Biology University of Rochester Medical Center Rochester 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