{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T08:34:05Z","timestamp":1774773245065,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002160","name":"Jain Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002160","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Limb\u2013girdle muscular dystrophy (MD) type R2 (LGMDR2, formerly LGMD2B) is an autosomal recessive form of MD caused by variants in the dysferlin gene, <jats:italic>DYSF<\/jats:italic>. It leads to slow proximal and distal muscle weakening that generally results in loss of ambulation around early adulthood but without the lethal cardiorespiratory dysfunction observed in the more severe Duchenne MD. How loss of dysferlin causes muscle fibre death is poorly understood, but recent evidence suggests a link between muscle wasting and loss of muscle cholesterol homeostasis with circulating lipoprotein abnormalities in many forms of MD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cross\u2010sectional circulating total cholesterol (CHOL), high\u2010density lipoprotein\u2010associated cholesterol (HDL\u2010C), non\u2010HDL\u2010C, creatine kinase (CK), transaminase levels and bilirubin were collected as part of the Jain Clinical Outcomes Study of Dysferlinopathy, a large multicentre LGMDR2 patient cohort (<jats:italic>N<\/jats:italic>\u2009=\u2009188), along with ambulatory function values.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report that 43%, 49% and 50% of male patients were found to have abnormal circulating CHOL, HDL\u2010C and non\u2010HDL\u2010C levels, respectively, whereas in female patients 39%, 37% and 30% of values were in the abnormal range. Overall, 68% of the total cohort had at least one abnormal cholesterol value (78% of males and 60% of females) and 89% of male CHOL\/HDL\u2010C ratios were in the suboptimal range (above 3.5). Although most patients were ambulant, the severity of circulating lipid abnormalities did not correlate with early loss of ambulation. Transaminase levels were lower in late\u2010stage LGMDR2 samples, whereas bilirubin remained unchanged, suggesting a low muscular mass rather than hepatic origin and the absence of major liver damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Data from the largest natural history cohort of LGMDR2 patients support the concept that dyslipidemia is a comorbidity of LGMDR2, and the causal role of cholesterol abnormalities in muscle death should be further investigated.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.70042","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T09:16:18Z","timestamp":1755249378000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["High\u2010Density Lipoprotein\u2010Associated Cholesterol Abnormalities in a Clinical Outcomes Study of Dysferlin\u2010Deficient Limb\u2013Girdle Muscular Dystrophy Type R2"],"prefix":"10.1002","volume":"16","author":[{"given":"Zoe","family":"White","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Pharmacology &amp; Therapeutics University of British Columbia (UBC)  Vancouver Canada"},{"name":"UBC Centre for Heart Lung Innovation St. Paul's Hospital  Vancouver Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Rufibach","sequence":"additional","affiliation":[{"name":"Jain Foundation  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather\u00a0Gordish","family":"Dressman","sequence":"additional","affiliation":[{"name":"Center for Translational Science, Division of Biostatistics and Study Methodology Children's National Health System  Washington District of Columbia USA"},{"name":"Pediatrics, Epidemiology and Biostatistics George Washington University  Washington District of Columbia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Hilsden","sequence":"additional","affiliation":[{"name":"The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute Newcastle University and Newcastle Hospitals NHS Foundation Trust  Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Cox","sequence":"additional","affiliation":[{"name":"The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute Newcastle University and Newcastle Hospitals NHS Foundation Trust  Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Spuler","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Muscle Research Unit Experimental and Clinical Research Center, a Joint Cooperation of the Charit\u00e9 Medical Faculty and the Max Delbr\u00fcck Center for Molecular Medicine  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John\u00a0W.","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences Stanford University School of Medicine  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristi\u00a0J.","family":"Jones","sequence":"additional","affiliation":[{"name":"The Children's Hospital at Westmead The University of Sydney  Sydney New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana\u00a0X.","family":"Bharucha\u2010Goebel","sequence":"additional","affiliation":[{"name":"Department of Neurology Children's National Health System  Washington District of Columbia USA"},{"name":"National Institutes of Health (NINDS)  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuelle","family":"Salort\u2010Campana","sequence":"additional","affiliation":[{"name":"Neuromuscular and ALS Reference Center of Marseille La Timone University Hospital  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Pestronk","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maggie\u00a0C.","family":"Walter","sequence":"additional","affiliation":[{"name":"Friedrich\u2010Baur\u2010Institute, Department of Neurology Ludwig Maximilian University of Munich  Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Paradas","sequence":"additional","affiliation":[{"name":"Neuromuscular Unit, Department of Neurology Hospital U. 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