{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T21:16:26Z","timestamp":1792617386085,"version":"4.5.0"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:00:00Z","timestamp":1743206400000},"content-version":"vor","delay-in-days":87,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p><jats:bold>Abstract:<\/jats:bold> Limb\u2013girdle muscular dystrophy Type 2A\/R1 or calpain\u20103 deficiency is the most common autosomal recessive limb\u2013girdle muscular dystrophy. However, in recent years, autosomal dominant cases and families with calpain\u20103 deficiency have been reported, and there is an emerging interest in looking for single variants in the calpain\u20103 gene in mildly to moderately affected patients with limb\u2013girdle muscular dystrophy without biallelic gene variants in <jats:italic>CAPN3<\/jats:italic>. Here, we report four cases with creatine kinase levels above 1500\u2009U\/L, mild\u2010to\u2010moderate proximal weakness, waddling gait, and scapular winging. Two patients, a son and his father, are heterozygous for the <jats:italic>CAPN3<\/jats:italic> variant c.304C&gt;T; p.(Pro102Ser), which has previously been reported in patients with compound heterozygous variants in <jats:italic>CAPN3<\/jats:italic>. The third and fourth patients were heterozygous for c.1371C&gt;G; p.(Asn457Lys) and c.1490C&gt;T; p.Ala497_Glu508del, respectively, neither of which has been reported before. All four patients had a near\u2010complete loss of calpain\u20103 as determined by western blotting. While inherited autosomal dominant calpainopathy has now been firmly established, additional single cases of dominant calpainopathy are likely to emerge; some will be associated with clinical findings from parents or siblings, while others will arise from spontaneous mutations, but nevertheless with similar clinical findings of mild\u2010to\u2010moderate proximal weakness, increased level of creatine kinase, and near\u2010complete loss of calpain\u20103 protein in affected individuals. This report expands the known number of variants causing dominant calpainopathy from 8 to 11 that appears to exclusively reside in two out of four domains that make up calpain\u20103. This information could aid in determining whether a <jats:italic>CAPN3<\/jats:italic> variant of unknown significance is pathological.<\/jats:p>","DOI":"10.1155\/humu\/9301465","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T09:34:50Z","timestamp":1743240890000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Variants in CAPN3 Causing Autosomal Dominant Limb\u2013Girdle Muscular Dystrophy Combined With Calpain\u20103 Deficiency"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9330-668X","authenticated-orcid":false,"given":"Thomas","family":"Krag","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9817-1533","authenticated-orcid":false,"given":"Emily","family":"Nasho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9587-471X","authenticated-orcid":false,"given":"Lauren","family":"Brady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0524-4827","authenticated-orcid":false,"given":"Camille","family":"Verebi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"France","family":"Leturcq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7871-8600","authenticated-orcid":false,"given":"Edoardo","family":"Malfatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8436-7744","authenticated-orcid":false,"given":"Morten","family":"Duno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0312-3746","authenticated-orcid":false,"given":"Mark","family":"Tarnopolsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6144-8544","authenticated-orcid":false,"given":"John","family":"Vissing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,29]]},"reference":[{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2004.11.003"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90368-2"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-13-43"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708262200"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.36185\/2532-1900-024"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww133"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.649"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.25970"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24066"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51193"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12624"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2021.11.011"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-023-00728-6"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808655200"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1411959111"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.028738"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24491"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-023-00451-1"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12663"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2015.09.010"}],"container-title":["Human 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