{"id":775,"date":"2015-07-01T18:31:15","date_gmt":"2015-07-01T18:31:15","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/jmg\/?p=775"},"modified":"2015-07-01T18:31:15","modified_gmt":"2015-07-01T18:31:15","slug":"a-casq1-founder-mutation-in-3-italian-families-with-protein-aggregate-myopathy-and-hyperckaemia","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/jmg\/2015\/07\/01\/a-casq1-founder-mutation-in-3-italian-families-with-protein-aggregate-myopathy-and-hyperckaemia\/","title":{"rendered":"A CASQ1 founder mutation in 3 Italian families with protein aggregate myopathy and hyperCKaemia"},"content":{"rendered":"<p>Chronic elevation of serum creatine kinase (CK) is a common manifestation of neuromuscular disorders and may precede disease clinical expression, or remain asymptomatic. In 3 Italian families having high CK, mild myopathy, and calsequestrin-positive inclusions in muscle fibers, exome and Sanger sequencing and linkage analysis revealed a founder mutation in the <em>CASQ1<\/em> gene. Immunocytochemistry, electron microscopy, biochemistry, and transfected cell line investigations showed a tendency of the mutated calsequestrin to form aggregates. <em>CASQ1<\/em> mutations may go undiagnosed if a muscle biopsy is not taken, and the condition could be more frequent than supposed in patients with familial hyperCKemia. (By Dr. Marina Mora, <a href=\"http:\/\/jmg.bmj.com\/content\/early\/2015\/07\/01\/jmedgenet-2014-102882\">http:\/\/jmg.bmj.com\/content\/early\/2015\/07\/01\/jmedgenet-2014-102882<\/a> )<\/p>\n<p><a href=\"https:\/\/stg-blogs.bmj.com\/jmg\/files\/2015\/07\/Fig-1.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-medium wp-image-776\" src=\"https:\/\/stg-blogs.bmj.com\/jmg\/files\/2015\/07\/Fig-1-283x300.jpg\" alt=\"Fig 1\" width=\"283\" height=\"300\" srcset=\"https:\/\/stg-blogs.bmj.com\/jmg\/files\/2015\/07\/Fig-1-283x300.jpg 283w, https:\/\/stg-blogs.bmj.com\/jmg\/files\/2015\/07\/Fig-1.jpg 957w\" sizes=\"auto, (max-width: 283px) 100vw, 283px\" \/><\/a><\/p>\n<p>(Muscle histopathology. in CASQ1 mutated\u00a0 patients\u00a0 (A)\u00a0 Gomori trichrome and (B)\u00a0 H&amp;E staining show several sarcoplasmic vacuoles, that, by electron microscopy (C,D) appear as large, often membrane-limited inclusions of variable size, shape and electron density, forming aggregations often lobular; (E) immunohistochemistry shows positivity of vacuoles to calsequestrin and SERCA1.)<!--TrendMD v2.4.8--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Chronic elevation of serum creatine kinase (CK) is a common manifestation of neuromuscular disorders and may precede disease clinical expression, or remain asymptomatic. In 3 Italian families having high CK, mild myopathy, and calsequestrin-positive inclusions in muscle fibers, exome and Sanger sequencing and linkage analysis revealed a founder mutation in the CASQ1 gene. Immunocytochemistry, electron [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/jmg\/2015\/07\/01\/a-casq1-founder-mutation-in-3-italian-families-with-protein-aggregate-myopathy-and-hyperckaemia\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-775","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/posts\/775","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/comments?post=775"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/posts\/775\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/media?parent=775"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/categories?post=775"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/jmg\/wp-json\/wp\/v2\/tags?post=775"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}