{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:58:15Z","timestamp":1772758695281,"version":"3.50.1"},"reference-count":17,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T00:00:00Z","timestamp":1722816000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Case Reports"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Key Clinical Message<\/jats:title><jats:sec><jats:label\/><jats:p>Homozygous variants of Calcium Voltage\u2010Gated Channel Subunit Alpha1 S (CACNA1S) gene mutation were previously identified as causes of periodic paralysis and congenital early\u2010onset myopathy, while it could be manifested as a late\u2010onset congenital core myopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Calcium Voltage\u2010Gated Channel Subunit Alpha1 S (CACNA1S) gene mutation has been linked to various neuromuscular conditions in recent years. Congenital myopathy with core\u2010like features is one of the cardinal associations reported previously, causing severe respiratory insufficiency and death in neonates. Informed consent was received from the patients. Subsequently, peripheral blood leukocytes were utilized to extract genomic DNA. Moreover, exome enrichment was implemented through the Twist Human Core Exome Kit (Twist Bioscience) and exome sequenced using Illumina NovaSeq 6000 platform (Illumina, San Diego, CA, USA). Sanger sequencing using BIG Dye Terminators confirmed the presence of the final variant. Finally, the candidate variants were classified based on the American College of Medical Genetics and Genomics (ACMG) guidelines. In this report, we describe two siblings, who presented with childhood and late\u2010onset progressive muscle weakness, and had a homozygous variant in exon 2 of the CACNA1S gene defined as c.188C\u2009&gt;\u2009A (p.Ala63Asp) (NM_000069.3). The SIFT, Polyphen2, CADD PHRED, and Mutation Taster analysis tools classified the variant as pathogenic\/damaging. The muscle biopsy of the younger brother revealed intermyofibrillar network pattern disruption as cytoplasmic core\u2010like lesions. The muscle magnetic resonance imaging (MRI) reported grade IIa and IIb fatty changes. Finally, the electromyography (EMG) findings suggested a myopathic change pattern. This report illustrates the clinical variability in CACNA1S\u2010related myopathy by reviewing prior reports and adding newly found aspects, additionally expanding the gene defects associated with core myopathy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ccr3.9251","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T11:24:18Z","timestamp":1722857058000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Core myopathy in two siblings with a biallelic variant in the CACNA1S gene\u2014A case series study"],"prefix":"10.1002","volume":"12","author":[{"given":"Tara","family":"Khoeini","sequence":"first","affiliation":[{"name":"Department of Neurology, Firoozgar Hospital Iran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8467-4728","authenticated-orcid":false,"given":"Ariana","family":"Kariminejad","sequence":"additional","affiliation":[{"name":"Kariminejad\u2010Najmabadi Pathology &amp; Genetics Center  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yalda","family":"Nilipour","sequence":"additional","affiliation":[{"name":"Pediatric Pathology Research Center Research Institute for Children's Health, Shahid Beheshti University of Medical Sciences  Tehran Iran"},{"name":"Neuromuscular Research Center Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3383-9710","authenticated-orcid":false,"given":"Armin","family":"Ariaei","sequence":"additional","affiliation":[{"name":"School of Medicine Iran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6084-7778","authenticated-orcid":false,"given":"Hossein","family":"Najmabadi","sequence":"additional","affiliation":[{"name":"Kariminejad\u2010Najmabadi Pathology &amp; Genetics Center  Tehran Iran"},{"name":"Genetics Research Center University of Social Welfare &amp; Rehabilitation Science  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mojtaba","family":"Arabshahi","sequence":"additional","affiliation":[{"name":"Radiology Department, Shohada Tajrish Hospital Shahid Beheshti University of Medical Science  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehrshid","family":"Faraji\u00a0Zonooz","sequence":"additional","affiliation":[{"name":"Kariminejad\u2010Najmabadi Pathology &amp; Genetics Center  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bahram","family":"Haghi\u00a0Ashtiani","sequence":"additional","affiliation":[{"name":"Department of Neurology, Firoozgar Hospital Iran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,8,5]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2013.11.003"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-014-0300-3"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/fpc.0000000000000393"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.30699\/jambs.31.148.415"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0960-8966(02)00023-8"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.3.1215"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1110s43"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.142"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1656-8"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3233\/jnd-190383"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.4103\/ijpm.ijpm_1031_21"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.4.5"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a023754"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2023.12.014"}],"container-title":["Clinical Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ccr3.9251","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T04:29:16Z","timestamp":1726288156000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ccr3.9251"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8]]},"references-count":17,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/ccr3.9251"],"URL":"https:\/\/doi.org\/10.1002\/ccr3.9251","archive":["Portico"],"relation":{},"ISSN":["2050-0904","2050-0904"],"issn-type":[{"value":"2050-0904","type":"print"},{"value":"2050-0904","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8]]},"assertion":[{"value":"2024-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e9251"}}