{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:33:20Z","timestamp":1788863600125,"version":"build-2803163510"},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI21\/00047"],"award-info":[{"award-number":["PI21\/00047"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015496","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas","doi-asserted-by":"publisher","award":["CB06\/05\/1126"],"award-info":[{"award-number":["CB06\/05\/1126"]}],"id":[{"id":"10.13039\/501100015496","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>Limb\u2010girdle muscular dystrophy R1 (LGMDR1) calpain 3\u2010related usually presents as a recessively transmitted weakness of proximal limb\u2010girdle muscles due to pathogenic variants in the <jats:italic>CAPN3<\/jats:italic> gene. Pathogenic variants in this gene have also been found in patients with an autosomal dominantly inherited transmission pattern (LGMDD4). The mechanism underlying this difference in transmission patterns has not yet been elucidated. Camptocormia, progressive limb weakness, myalgia, back pain, and increased CK levels are common clinical features associated with dominant forms. The p.Lys254del pathogenic variant was associated with camptocormia in two LGMDD4 families. This study aimed to present carriers found in recessively transmitted LGMDR1 families bearing the p.Lys254del variant that do not show muscle weakness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DNA sequencing was performed on exon 5 of <jats:italic>CAPN3<\/jats:italic> in family members to establish the carrier status of the pathogenic variant. They were evaluated clinically and MRI was performed when available.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two families presented with the p.Lys254del pathogenic variant in a homozygous or compound heterozygous state. Family members carrying only the pathogenic variant in the heterozygous state did not demonstrate the myopathic characteristics described in dominant patients. Camptocormia and other severe clinical symptoms were not observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We conclude that the p.Lys254del pathogenic variant per se cannot be solely responsible for camptocormia in dominant patients. Other undisclosed factors may regulate the phenotype associated with the dominant inheritance pattern in <jats:italic>CAPN3<\/jats:italic> pathogenic variant carriers.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.28045","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T10:00:23Z","timestamp":1706781623000},"page":"472-476","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The <scp>CAPN3 p.Lys 254del<\/scp> variant is not always associated with dominant <scp>CAPN3<\/scp>\u2010related muscular dystrophy"],"prefix":"10.1002","volume":"69","author":[{"given":"Andrea","family":"Valls","sequence":"first","affiliation":[{"name":"Neurosciences Area Biodonostia Health Research Institute  San Sebastian Spain"},{"name":"CIBERNED, CIBER, Spanish Ministry of Science &amp; Innovation, Carlos III Health Institute  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerardo","family":"Guti\u00e9rrez\u2010Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"CIBERNED, CIBER, Spanish Ministry of Science &amp; Innovation, Carlos III Health Institute  Madrid Spain"},{"name":"Department of Neurology Hospital Universitario Infanta Sof\u00eda  Madrid Spain"},{"name":"Neuromuscular Diseases Unit Universidad Europea de Madrid  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agust\u00edn","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Hospital P\u00fablico da Mari\u00f1a\u2013Burela  Burela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Ruiz\u2010Rold\u00e1n","sequence":"additional","affiliation":[{"name":"Neurosciences Area Biodonostia Health Research Institute  San Sebastian Spain"},{"name":"CIBERNED, CIBER, Spanish Ministry of Science &amp; Innovation, Carlos III Health Institute  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Cama\u00f1o","sequence":"additional","affiliation":[{"name":"Neurosciences Area Biodonostia Health Research Institute  San Sebastian Spain"},{"name":"CIBERNED, CIBER, Spanish Ministry of Science &amp; Innovation, Carlos III Health Institute  Madrid Spain"},{"name":"Molecular Diagnostics Platform, Biodonostia Health Research Institute  San Sebastian Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo","family":"L\u00f3pez de Munain","sequence":"additional","affiliation":[{"name":"Neurosciences Area Biodonostia Health Research Institute  San Sebastian Spain"},{"name":"CIBERNED, CIBER, Spanish Ministry of Science &amp; Innovation, Carlos III Health Institute  Madrid Spain"},{"name":"Department of Neurology Donostialdea Integrated Health Organisation, Osakidetza  San Sebastian Spain"},{"name":"Department of Neurosciences University of the Basque Country UPV\u2010EHU  San Sebastian Spain"},{"name":"Faculty of Medicine University of Deusto  Bilbao Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0704-1150","authenticated-orcid":false,"given":"Amets","family":"S\u00e1enz","sequence":"additional","affiliation":[{"name":"Neurosciences Area Biodonostia Health Research Institute  San Sebastian Spain"},{"name":"CIBERNED, CIBER, Spanish Ministry of Science &amp; 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