4636 lines
420 KiB
Text
4636 lines
420 KiB
Text
|
|
|
|
|
|
|
|
|
|
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
|
|
|
|
<head>
|
|
|
|
|
|
|
|
<!--
|
|
################################# CRAWLER WARNING #################################
|
|
|
|
- The terms of service and the robots.txt file disallows crawling of this site,
|
|
please see https://omim.org/help/agreement for more information.
|
|
|
|
- A number of data files are available for download at https://omim.org/downloads.
|
|
|
|
- We have an API which you can learn about at https://omim.org/help/api and register
|
|
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
|
|
|
|
- You should feel free to contact us at https://omim.org/contact to figure out the best
|
|
approach to getting the data you need for your work.
|
|
|
|
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
|
|
|
|
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
|
|
DISTRIBUTED CRAWLS OF THIS SITE.
|
|
|
|
################################# CRAWLER WARNING #################################
|
|
-->
|
|
|
|
|
|
|
|
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
|
|
<meta http-equiv="cache-control" content="no-cache" />
|
|
<meta http-equiv="pragma" content="no-cache" />
|
|
<meta name="robots" content="index, follow" />
|
|
|
|
|
|
<meta name="viewport" content="width=device-width, initial-scale=1" />
|
|
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
|
|
|
|
|
|
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
|
|
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
|
|
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
|
|
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
|
|
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
|
|
contain copious links to other genetics resources." />
|
|
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
|
|
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
|
|
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
|
|
<meta name="theme-color" content="#333333" />
|
|
<link rel="icon" href="/static/omim/favicon.png" />
|
|
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
|
|
<link rel="manifest" href="/static/omim/manifest.json" />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script id='mimBrowserCapability'>
|
|
function _0x5069(){const _0x4b1387=['91sZIeLc','mimBrowserCapability','15627zshTnf','710004yxXedd','34LxqNYj','match','disconnect','1755955rnzTod','observe','1206216ZRfBWB','575728fqgsYy','webdriver','documentElement','close','open','3086704utbakv','7984143PpiTpt'];_0x5069=function(){return _0x4b1387;};return _0x5069();}function _0xe429(_0x472ead,_0x43eb70){const _0x506916=_0x5069();return _0xe429=function(_0xe42949,_0x1aaefc){_0xe42949=_0xe42949-0x1a9;let _0xe6add8=_0x506916[_0xe42949];return _0xe6add8;},_0xe429(_0x472ead,_0x43eb70);}(function(_0x337daa,_0x401915){const _0x293f03=_0xe429,_0x5811dd=_0x337daa();while(!![]){try{const _0x3dc3a3=parseInt(_0x293f03(0x1b4))/0x1*(-parseInt(_0x293f03(0x1b6))/0x2)+parseInt(_0x293f03(0x1b5))/0x3+parseInt(_0x293f03(0x1b0))/0x4+-parseInt(_0x293f03(0x1b9))/0x5+parseInt(_0x293f03(0x1aa))/0x6+-parseInt(_0x293f03(0x1b2))/0x7*(parseInt(_0x293f03(0x1ab))/0x8)+parseInt(_0x293f03(0x1b1))/0x9;if(_0x3dc3a3===_0x401915)break;else _0x5811dd['push'](_0x5811dd['shift']());}catch(_0x4dd27b){_0x5811dd['push'](_0x5811dd['shift']());}}}(_0x5069,0x84d63),(function(){const _0x9e4c5f=_0xe429,_0x363a26=new MutationObserver(function(){const _0x458b09=_0xe429;if(document!==null){let _0x2f0621=![];navigator[_0x458b09(0x1ac)]!==![]&&(_0x2f0621=!![]);for(const _0x427dda in window){_0x427dda[_0x458b09(0x1b7)](/cdc_[a-z0-9]/ig)&&(_0x2f0621=!![]);}_0x2f0621===!![]?document[_0x458b09(0x1af)]()[_0x458b09(0x1ae)]():(_0x363a26[_0x458b09(0x1b8)](),document['getElementById'](_0x458b09(0x1b3))['remove']());}});_0x363a26[_0x9e4c5f(0x1a9)](document[_0x9e4c5f(0x1ad)],{'childList':!![]});}()));
|
|
</script>
|
|
|
|
|
|
|
|
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
|
|
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
|
|
|
|
<link rel="preconnect" href="https://www.googletagmanager.com" />
|
|
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
|
|
<script>
|
|
window.dataLayer = window.dataLayer || [];
|
|
function gtag(){window.dataLayer.push(arguments);}
|
|
gtag("js", new Date());
|
|
gtag("config", "G-HMPSQC23JJ");
|
|
</script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
|
|
|
|
|
|
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
|
|
|
|
|
|
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimBootstrapDeviceSize">
|
|
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
|
|
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
|
|
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
|
|
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
|
|
</div>
|
|
|
|
|
|
|
|
<title>
|
|
|
|
Entry
|
|
|
|
- *114240 - CALPAIN 3; CAPN3
|
|
|
|
|
|
- OMIM
|
|
|
|
</title>
|
|
|
|
|
|
|
|
</head>
|
|
|
|
<body>
|
|
<div id="mimBody">
|
|
|
|
|
|
|
|
<div id="mimHeader" class="hidden-print">
|
|
|
|
|
|
|
|
<nav class="navbar navbar-inverse navbar-fixed-top mim-navbar-background">
|
|
<div class="container-fluid">
|
|
|
|
<!-- Brand and toggle get grouped for better mobile display -->
|
|
<div class="navbar-header">
|
|
<button type="button" class="navbar-toggle collapsed" data-toggle="collapse" data-target="#mimNavbarCollapse" aria-expanded="false">
|
|
<span class="sr-only"> Toggle navigation </span>
|
|
<span class="icon-bar"></span>
|
|
<span class="icon-bar"></span>
|
|
<span class="icon-bar"></span>
|
|
</button>
|
|
<a class="navbar-brand" href="/"><img alt="OMIM" src="/static/omim/icons/OMIM_davinciman.001.png" height="30" width="30"></a>
|
|
</div>
|
|
|
|
<div id="mimNavbarCollapse" class="collapse navbar-collapse">
|
|
|
|
<ul class="nav navbar-nav">
|
|
|
|
|
|
<li>
|
|
<a href="/help/about"><span class="mim-navbar-menu-font"> About </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimStatisticsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Statistics <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="statisticsDropdown">
|
|
<li>
|
|
<a href="/statistics/update"> Update List </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/entry"> Entry Statistics </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/geneMap"> Phenotype-Gene Statistics </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/paceGraph"> Pace of Gene Discovery Graph </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDownloadsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Downloads <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="downloadsDropdown">
|
|
|
|
<li>
|
|
<a href="/downloads/"> Register for Downloads </a>
|
|
</li>
|
|
<li>
|
|
<a href="/api"> Register for API Access </a>
|
|
</li>
|
|
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="/contact?mimNumber=114240"><span class="mim-navbar-menu-font"> Contact Us </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li>
|
|
|
|
<a href="/mimmatch/">
|
|
|
|
<span class="mim-navbar-menu-font">
|
|
<span class="mim-tip-bottom" qtip_title="<strong>MIMmatch</strong>" qtip_text="MIMmatch is a way to follow OMIM entries that interest you and to find other researchers who may share interest in the same entries. <br /><br />A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.">
|
|
MIMmatch
|
|
</span>
|
|
</span>
|
|
</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDonateDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Donate <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="donateDropdown">
|
|
<li>
|
|
<a href="https://secure.jhu.edu/form/OMIM" target="_blank" onclick="gtag('event', 'mim_donation', {'destination': 'secure.jhu.edu'})"> Donate! </a>
|
|
</li>
|
|
<li>
|
|
<a href="/donors"> Donors </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimHelpDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Help <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="helpDropdown">
|
|
<li>
|
|
<a href="/help/faq"> Frequently Asked Questions (FAQs) </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/search"> Search Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/linking"> Linking Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/api"> API Help </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/external"> External Links </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/agreement"> Use Agreement </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/copyright"> Copyright </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="#" id="mimShowTips" class="mim-tip-hint" title="Click to reveal all tips on the page. You can also hover over individual elements to reveal the tip."><span class="mim-navbar-menu-font"><span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span></span></a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimSearch" class="hidden-print">
|
|
|
|
<div class="container">
|
|
|
|
<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
|
|
|
|
<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
|
|
<input type="hidden" id="mimSearchStart" name="start" value="1" />
|
|
<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
|
|
<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
|
|
<div class="form-group">
|
|
<div class="input-group">
|
|
<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
|
|
<div class="input-group-btn">
|
|
<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
|
|
<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
|
|
<ul class="dropdown-menu dropdown-menu-right">
|
|
<li class="dropdown-header">
|
|
Advanced Search
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/entry"> OMIM </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/geneMap"> Gene Map </a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/history"> Search History </a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
</div>
|
|
</div>
|
|
<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
|
|
<span class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</form>
|
|
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
<!-- <div id="mimSearch"> -->
|
|
|
|
|
|
|
|
|
|
<div id="mimContent">
|
|
|
|
|
|
|
|
<div class="container hidden-print">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
|
|
<div id="mimAlertBanner">
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
|
|
|
|
<div id="mimFloatingTocMenu" class="small" role="navigation">
|
|
|
|
<p>
|
|
<span class="h4">*114240</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/114240">Table View</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000092529;t=ENST00000397163" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=825" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=114240" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000092529;t=ENST00000397163" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000070,NM_024344,NM_173087,NM_173088,NM_173089,NM_173090" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000070" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=114240" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://hprd.org/summary?hprd_id=00255&isoform_id=00255_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.proteinatlas.org/search/CAPN3" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/protein/791040,1345664,4557405,4704752,7684607,13097609,13111993,13436131,17483736,27765072,27765074,27765076,27765078,27765080,30583483,45501327,58258010,71682262,72533379,78070758,118763864,127795883,133777180,148921535,148922224,194375722,209574302,209574304,218471944,218471946,218471948,218471950,218471952,218471954,218471956,957949053,957949056,957949059" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.uniprot.org/uniprotkb/P20807" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Gene Info</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="http://biogps.org/#goto=genereport&id=825" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000092529;t=ENST00000397163" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=CAPN3" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=CAPN3" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+825" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
<dd><a href="http://v1.marrvel.org/search/gene/CAPN3" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
|
|
|
|
|
|
|
|
<dd><a href="https://monarchinitiative.org/NCBIGene:825" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gene/825" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr15&hgg_gene=ENST00000549793.5&hgg_start=42359501&hgg_end=42412317&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:1480" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:1480" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/gene/capn3" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=114240[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=114240[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.deciphergenomics.org/gene/CAPN3/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000092529" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ebi.ac.uk/gwas/search?query=CAPN3" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.gwascentral.org/search?q=CAPN3" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=CAPN3" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.LOVD.nl/CAPN3" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=CAPN3&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.pharmgkb.org/gene/PA26061" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Animal Models</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.alliancegenome.org/gene/HGNC:1480" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://flybase.org/reports/FBgn0012051.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:107437" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://v1.marrvel.org/search/gene/CAPN3#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.informatics.jax.org/marker/MGI:107437" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gene/825/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://omia.org/OMIA002611/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=825" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
|
|
<div id="mimWormbaseGeneFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00000542;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00000542 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00000544;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00000544 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00000545;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00000545 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00000546;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00000546 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00000547;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00000547 </a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-040912-97" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cell Lines</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:114240" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:825" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://reactome.org/content/query?q=CAPN3&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 1279886003, 370474006, 715341003<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> G71.032<br />
|
|
|
|
|
|
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
114240
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
CALPAIN 3; CAPN3
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
CALPAIN, LARGE POLYPEPTIDE L3<br />
|
|
CALPAIN III, LARGE SUBUNIT; CANPL3<br />
|
|
CALCIUM-ACTIVATED NEUTRAL PROTEASE 3, MUSCLE-SPECIFIC, LARGE SUBUNIT; CANP3<br />
|
|
p94
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=CAPN3" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CAPN3</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/15/133?start=-3&limit=10&highlight=133">15q15.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr15:42359501-42412317&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">15:42,359,501-42,412,317</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=618129,253600" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/15/133?start=-3&limit=10&highlight=133">
|
|
15q15.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Muscular dystrophy, limb-girdle, autosomal dominant 4
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/618129"> 618129 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Muscular dystrophy, limb-girdle, autosomal recessive 1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/253600"> 253600 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/114240" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/114240" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>The CAPN3 gene encodes calpain-3. The calpains, or calcium-activated neutral proteases (<a href="https://enzyme.expasy.org/EC/3.4.22.17" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 3.4.22.17</a>), are nonlysosomal intracellular cysteine proteases. Mammalian calpains are heterodimers composed of a ubiquitous 80-kD large subunit (e.g., CAPN1, <a href="/entry/114220">114220</a> and CAPN2, <a href="/entry/114230">114230</a>) and a common small 30-kD subunit (CAPNS1; <a href="/entry/114170">114170</a>). CAPN3 is a muscle-specific large subunit (<a href="#22" class="mim-tip-reference" title="Sorimachi, H., Imajoh-Ohmi, S., Emori, Y., Kawasaki, H., Ohno, S., Minami, Y., Suzuki, K. <strong>Molecular cloning of a novel mammalian calcium-dependent protease distinct from both m- and mu-types: specific expression of the mRNA in skeletal muscle.</strong> J. Biol. Chem. 264: 20106-20111, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2555341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2555341</a>]" pmid="2555341">Sorimachi et al., 1989</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2555341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#22" class="mim-tip-reference" title="Sorimachi, H., Imajoh-Ohmi, S., Emori, Y., Kawasaki, H., Ohno, S., Minami, Y., Suzuki, K. <strong>Molecular cloning of a novel mammalian calcium-dependent protease distinct from both m- and mu-types: specific expression of the mRNA in skeletal muscle.</strong> J. Biol. Chem. 264: 20106-20111, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2555341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2555341</a>]" pmid="2555341">Sorimachi et al. (1989)</a> isolated a clone corresponding to a novel member of the CAPN (symbolized CANP by them) large subunit family from human and rat skeletal muscle cDNA libraries. The deduced protein (p94), corresponding to CAPN3, contains 821 amino acid residues, has a molecular mass of 94 kD, and shows significant sequence homology with other large subunits. The protein could be divided into 4 domains (I to IV) as reported for the CANP large subunit family. Domains II and IV are potential cysteine protease and calcium-binding domains, respectively, and have sequences homologous to the corresponding domains of other CANP large subunits. However, domain I of p94 is significantly different from others. In addition, p94 contains 2 unique sequences of 62 and 77 residues in domains II and III, respectively. In contrast to the ubiquitous expression of other large subunits, Northern blot analysis detected a p94 mRNA in skeletal muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2555341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Richard, I., Broux, O., Allamand, V., Fougerousse, F., Chiannilkulchai, N., Bourg, N., Brenguier, L., Devaud, C., Pasturaud, P., Roudaut, C., Hillaire, D., Passos-Bueno, M.-R., Zatz, M., Tischfield, J. A., Fardeau, M., Jackson, C. E., Cohen, D., Beckmann, J. S. <strong>Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.</strong> Cell 81: 27-40, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7720071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7720071</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90368-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7720071">Richard et al. (1995)</a> identified the CAPN3 gene by positional cloning of a region on chromosome 15q containing the gene for autosomal recessive limb-girdle muscular dystrophy-1 (LGMDR1; <a href="/entry/253600">253600</a>). CAPN3 gene was a particularly attractive candidate because of its functional role in muscle. <a href="#20" class="mim-tip-reference" title="Richard, I., Broux, O., Allamand, V., Fougerousse, F., Chiannilkulchai, N., Bourg, N., Brenguier, L., Devaud, C., Pasturaud, P., Roudaut, C., Hillaire, D., Passos-Bueno, M.-R., Zatz, M., Tischfield, J. A., Fardeau, M., Jackson, C. E., Cohen, D., Beckmann, J. S. <strong>Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.</strong> Cell 81: 27-40, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7720071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7720071</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90368-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7720071">Richard et al. (1995)</a> reported a gene sequence that differed slightly from that reported by <a href="#22" class="mim-tip-reference" title="Sorimachi, H., Imajoh-Ohmi, S., Emori, Y., Kawasaki, H., Ohno, S., Minami, Y., Suzuki, K. <strong>Molecular cloning of a novel mammalian calcium-dependent protease distinct from both m- and mu-types: specific expression of the mRNA in skeletal muscle.</strong> J. Biol. Chem. 264: 20106-20111, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2555341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2555341</a>]" pmid="2555341">Sorimachi et al. (1989)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2555341+7720071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Blazquez, L., Azpitarte, M., Saenz, A., Goicoechea, M., Otaegui, D., Ferrer, X., Illa, I., Gutierrez-Rivas, E., Vilchez, J. J., Lopez de Munain, A. <strong>Characterization of novel CAPN3 isoforms in white blood cells: an alternative approach for limb-girdle muscular dystrophy 2A diagnosis.</strong> Neurogenetics 9: 173-182, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18563459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18563459</a>] [<a href="https://doi.org/10.1007/s10048-008-0129-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18563459">Blazquez et al. (2008)</a> identified 4 different CAPN3 mRNA transcripts in human white blood cells. Sequence analysis showed that exon 15 was always absent, whereas exons 6 and 16 could be present or not. There was only 1 transcript detected in muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18563459" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Richard, I., Beckmann, J. S. <strong>Molecular cloning of mouse Canp3, the gene associated with limb-girdle muscular dystrophy 2A in human.</strong> Mammalian Genome 7: 377-379, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8661728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8661728</a>] [<a href="https://doi.org/10.1007/s003359900108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8661728">Richard and Beckmann (1996)</a> found that the mouse Capn3 gene encodes an mRNA of a size similar to the human CANP3 mRNA. The mouse gene directs the synthesis of an 821-amino acid protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8661728" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneStructure" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneStructureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneStructureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#20" class="mim-tip-reference" title="Richard, I., Broux, O., Allamand, V., Fougerousse, F., Chiannilkulchai, N., Bourg, N., Brenguier, L., Devaud, C., Pasturaud, P., Roudaut, C., Hillaire, D., Passos-Bueno, M.-R., Zatz, M., Tischfield, J. A., Fardeau, M., Jackson, C. E., Cohen, D., Beckmann, J. S. <strong>Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.</strong> Cell 81: 27-40, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7720071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7720071</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90368-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7720071">Richard et al. (1995)</a> demonstrated that the CAPN3 gene contains 24 exons and extends over 40 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7720071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#14" class="mim-tip-reference" title="Ohno, S., Minoshima, S., Kudoh, J., Fukuyama, R., Ohmi-Imajoh, S., Suzuki, K., Shimizu, Y., Shimizu, N. <strong>Four genes for the calpain family locate on four distinct human chromosomes.</strong> Cytogenet. Cell Genet. 53: 225-229, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2209092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2209092</a>] [<a href="https://doi.org/10.1159/000132937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2209092">Ohno et al. (1990)</a> mapped the CAPN3 gene to chromosome 15. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2209092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By somatic cell hybridization, <a href="#18" class="mim-tip-reference" title="Richard, I., Beckmann, J. S. <strong>Molecular cloning of mouse Canp3, the gene associated with limb-girdle muscular dystrophy 2A in human.</strong> Mammalian Genome 7: 377-379, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8661728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8661728</a>] [<a href="https://doi.org/10.1007/s003359900108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8661728">Richard and Beckmann (1996)</a> localized the mouse Capn3 gene to either chromosome 2 or chromosome 4. The results did not allow distinction between these 2 chromosomes, since all hybrids carrying mouse chromosome 2 also carried chromosome 4. The fact that isolated murine YACs amplified a sequence tagged site (STS) for the TYRO3 gene (<a href="/entry/600341">600341</a>), which maps to human chromosome 15, suggested to <a href="#18" class="mim-tip-reference" title="Richard, I., Beckmann, J. S. <strong>Molecular cloning of mouse Canp3, the gene associated with limb-girdle muscular dystrophy 2A in human.</strong> Mammalian Genome 7: 377-379, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8661728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8661728</a>] [<a href="https://doi.org/10.1007/s003359900108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8661728">Richard and Beckmann (1996)</a> that the 2 genes are adjacent in the mouse. Homology between mouse chromosome 2 and human chromosome 15 is well established by a number of examples of synteny; no homology of synteny has been demonstrated between human 15 and mouse 4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8661728" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneFunction" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneFunctionFold" id="mimGeneFunctionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneFunctionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneFunctionFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>In COS-1 cells, <a href="#6" class="mim-tip-reference" title="Huang, Y., de Morree, A., van Remoortere, A., Bushby, K., Frants, R. R., Dunnen, J. T., van der Maarel, S. <strong>Calpain 3 is a modulator of the dysferlin protein complex in skeletal muscle.</strong> Hum. Molec. Genet. 17: 1855-1866, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18334579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18334579</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18334579[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddn081" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18334579">Huang et al. (2008)</a> demonstrated that calpain-3 and AHNAK (<a href="/entry/103390">103390</a>) colocalize at the I-band near the A-I junction in skeletal muscle, that calpain-3 cleaves AHNAK, and that this cleavage results in decreased levels of AHNAK. Studies of AHNAK fusion protein constructs showed that calpain-3 can cleave AHNAK at 2 sites in the N terminus and 3 sites in the C terminus, but not at the central M region. Cleavage of AHNAK disrupted its binding to dysferlin (DYSF; <a href="/entry/603009">603009</a>) and myoferlin (FER1L3; <a href="/entry/604603">604603</a>). Skeletal muscle from 4 patients with autosomal recessive LGMD due to CAPN3 mutations (LGMDR1) showed increased levels of AHNAK at the sarcolemma and blood vessels. <a href="#6" class="mim-tip-reference" title="Huang, Y., de Morree, A., van Remoortere, A., Bushby, K., Frants, R. R., Dunnen, J. T., van der Maarel, S. <strong>Calpain 3 is a modulator of the dysferlin protein complex in skeletal muscle.</strong> Hum. Molec. Genet. 17: 1855-1866, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18334579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18334579</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18334579[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddn081" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18334579">Huang et al. (2008)</a> concluded that CAPN3 plays a role in the dysferlin protein complex and that disruption of CAPN3 function may affect muscle membrane repair and remodeling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18334579" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Sarparanta, J., Blandin, G., Charton, K., Vihola, A., Marchand, S., Milic, A., Hackman, P., Ehler, E., Richard, I., Udd, B. <strong>Interactions with M-band titin and calpain 3 link myospryn (CMYA5) to tibial and limb-girdle muscular dystrophies.</strong> J. Biol. Chem. 285: 30304-30315, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20634290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20634290</a>] [<a href="https://doi.org/10.1074/jbc.M110.108720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20634290">Sarparanta et al. (2010)</a> found that C-terminal domains of the muscle-specific protein myospryn (CMYA5; <a href="/entry/612193">612193</a>) interacted with calpain-3. Myospryn appeared to stabilize full-length calpain-3 against proteolytic autoactivation, and active calpain-3 used myospryn as a substrate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20634290" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Autosomal Recessive Limb-Girdle Muscular Dystrophy 1</em></strong></p><p>
|
|
By a mutation screen in families with autosomal recessive limb-girdle muscular dystrophy-1 (LGMDR1; <a href="/entry/253600">253600</a>), earlier designated LGMD2A, <a href="#20" class="mim-tip-reference" title="Richard, I., Broux, O., Allamand, V., Fougerousse, F., Chiannilkulchai, N., Bourg, N., Brenguier, L., Devaud, C., Pasturaud, P., Roudaut, C., Hillaire, D., Passos-Bueno, M.-R., Zatz, M., Tischfield, J. A., Fardeau, M., Jackson, C. E., Cohen, D., Beckmann, J. S. <strong>Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.</strong> Cell 81: 27-40, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7720071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7720071</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90368-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7720071">Richard et al. (1995)</a> identified biallelic mutations in the CAPN3 gene, including nonsense, splice site, frameshift, and missense mutations (see, e.g., <a href="#0001">114240.0001</a>, <a href="#0002">114240.0002</a>, and <a href="#0003">114240.0003</a>). The mutations segregated with the disorder in the families. Six of the mutations were found within an inbred population on Reunion Island, located in the Indian Ocean, and haplotype analysis suggested the existence of at least 1 more mutation in the group. The occurrence of multiple independent mutations in the isolated population on Reunion Island rather than the finding of an expected founder mutation was referred to as the 'Reunion paradox' by <a href="#20" class="mim-tip-reference" title="Richard, I., Broux, O., Allamand, V., Fougerousse, F., Chiannilkulchai, N., Bourg, N., Brenguier, L., Devaud, C., Pasturaud, P., Roudaut, C., Hillaire, D., Passos-Bueno, M.-R., Zatz, M., Tischfield, J. A., Fardeau, M., Jackson, C. E., Cohen, D., Beckmann, J. S. <strong>Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.</strong> Cell 81: 27-40, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7720071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7720071</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90368-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7720071">Richard et al. (1995)</a>. They suggested that LGMD2A, instead of being a monogenic disorder, might have a more complex inheritance pattern in which expression of calpain mutations is dependent on genetic background, either nuclear or mitochondrial; see INHERITANCE section in <a href="/entry/253600">253600</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7720071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Richard, I., Brenguier, L., Dincer, P., Roudaut, C., Bady, B., Burgunder, J.-M., Chemaly, R., Garcia, C. A., Halaby, G., Jackson, C. E., Kurnit, D. M., Lefranc, G., Legum, C., Loiselet, J., Merlini, L., Nivelon-Chevallier, A., Ollagnon-Roman, E., Restagno, G., Topaloglu, H., Beckmann, J. S. <strong>Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins.</strong> Am. J. Hum. Genet. 60: 1128-1138, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9150160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9150160</a>]" pmid="9150160">Richard et al. (1997)</a> studied 21 LGMD pedigrees of various origins: France, Israel, Lebanon, Switzerland, United States, Italy, and Turkey. Nine of the 23 families showed linkage to chromosome 15, whereas such linkage was excluded in 10 and was inconclusive in 4. A search for CAPN3 mutations uncovered 19 novel mutations in addition to the 16 described previously (see, e.g., <a href="#0004">114240.0004</a>; <a href="#0005">114240.0005</a>). A survey of clinical features showed great variability. All patients showed elevated serum creatine kinase in a range of 7 to 84 times the upper limit of normal, marked intra- and interfamilial phenotypic variability in age of onset (range 2.5 to 40 years), and loss of ambulation. For example, affected individuals in 1 family presented with a very mild phenotype, with onset at ages 30 and 40 years, and were still ambulatory at ages 54 and 66 years, respectively. In contrast, 2 Lebanese sibs had onset at age 6 years and had loss of independent walking at ages 13 years and 15 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9150160" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Fanin, M., Nascimbeni, A. C., Fulizio, L., Angelini, C. <strong>The frequency of limb girdle muscular dystrophy 2A in northeastern Italy.</strong> Neuromusc. Disord. 15: 218-224, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15725583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15725583</a>] [<a href="https://doi.org/10.1016/j.nmd.2004.11.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15725583">Fanin et al. (2005)</a> identified mutations in the CAPN3 gene in 70 (33%) of 214 patients with limb-girdle muscular dystrophy in Italy. The prevalence of LGMD2A was estimated at 9.47 per million inhabitants in northeastern Italy. Two founder mutations were identified (500delA, <a href="#0009">114240.0009</a>; R490Q, <a href="#0010">114240.0010</a>). <a href="#24" class="mim-tip-reference" title="Todorova, A., Georgieva, B., Tournev, I., Todorov, T., Bogdanova, N., Mitev, V., Mueller, C. R., Kremensky, I., Horst, J. <strong>A large deletion and novel point mutations in the calpain 3 gene (CAPN3) in Bulgarian LGMD2A patients.</strong> Neurogenetics 8: 225-229, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17318636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17318636</a>] [<a href="https://doi.org/10.1007/s10048-007-0083-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17318636">Todorova et al. (2007)</a> identified mutations in the CAPN3 gene in 20 (42%) of 48 unrelated Bulgarian patients with muscular dystrophy. Three novel and 6 recurrent mutations were identified. Forty percent of the patients were homozygous for the 500delA mutation, and 70% carried it on at least 1 allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17318636+15725583" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By high-throughput denaturing HPLC, <a href="#16" class="mim-tip-reference" title="Piluso, G., Politano, L., Aurino, S., Fanin, M., Ricci, E., Ventriglia, V. M., Belsito, A., Totaro, A., Saccone, V., Topaloglu, H., Nascimbeni, A. C., Fulizio, L., Broccolini, A., Canki-Klain, N., Comi, L. I., Nigro, G., Angelini, C., Nigro, V. <strong>Extensive scanning of the calpain-3 gene broadens the spectrum of LGMD2A phenotypes.</strong> J. Med. Genet. 42: 686-693, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16141003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16141003</a>] [<a href="https://doi.org/10.1136/jmg.2004.028738" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16141003">Piluso et al. (2005)</a> scanned the CAPN3 gene in 530 individuals with different grades of symptoms consistent with LGMD. They found 141 LGMD2A patients carrying 82 different CAPN3 mutations, of which 45 were novel. Females had a more favorable course than males. In 94% of the most severely affected LGMD2A patients, the defect was also discovered in the second allele. CAPN3 mutations were found in 35.1% of patients with classic LGMD phenotypes, 18.4% of atypical patients, and 12.6% of patients with high serum creatine kinase levels. <a href="#16" class="mim-tip-reference" title="Piluso, G., Politano, L., Aurino, S., Fanin, M., Ricci, E., Ventriglia, V. M., Belsito, A., Totaro, A., Saccone, V., Topaloglu, H., Nascimbeni, A. C., Fulizio, L., Broccolini, A., Canki-Klain, N., Comi, L. I., Nigro, G., Angelini, C., Nigro, V. <strong>Extensive scanning of the calpain-3 gene broadens the spectrum of LGMD2A phenotypes.</strong> J. Med. Genet. 42: 686-693, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16141003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16141003</a>] [<a href="https://doi.org/10.1136/jmg.2004.028738" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16141003">Piluso et al. (2005)</a> broadened the spectrum of LGMD2A phenotypes and set the carrier frequency at 1:103. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16141003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Among 46 European patients suspected to have LGMD2A based on Western blot results, <a href="#3" class="mim-tip-reference" title="Duno, M., Sveen, M.-L., Schwartz, M., Vissing, J. <strong>cDNA analyses of CAPN3 enhances mutation detection and reveals a low prevalence of LGMD2A patients in Denmark.</strong> Europ. J. Hum. Genet. 16: 935-940, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337726</a>] [<a href="https://doi.org/10.1038/ejhg.2008.47" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18337726">Duno et al. (2008)</a> found that 16 patients had mutations in the CAPN3 gene identified by both direct genomic sequencing and cDNA analysis. Both mutant alleles were demonstrated in 10 patients. A total of 16 mutations were identified, including 5 novel mutations. Only 3 of the genetically confirmed LGMD2A patients were of Danish origin, indicating a 5- to 6-fold lower prevalence in Denmark compared to other European countries. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18337726" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Prior to the identification of CAPN3 as the defective gene in LGMDR1, all identified molecular mechanisms in muscular dystrophies had involved structural components of muscle. CAPN3 appears to have a very rapid turnover mediated by autocatalysis, possibly reflecting the need for precise regulation of its activity. Furthermore, CAPN3 shows a nuclear localization, possibly mediated by the nuclear translocation signal in the IS2 region. <a href="#20" class="mim-tip-reference" title="Richard, I., Broux, O., Allamand, V., Fougerousse, F., Chiannilkulchai, N., Bourg, N., Brenguier, L., Devaud, C., Pasturaud, P., Roudaut, C., Hillaire, D., Passos-Bueno, M.-R., Zatz, M., Tischfield, J. A., Fardeau, M., Jackson, C. E., Cohen, D., Beckmann, J. S. <strong>Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.</strong> Cell 81: 27-40, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7720071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7720071</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90368-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7720071">Richard et al. (1995)</a> favored the idea that the CAPN3 protein is involved in the control of gene expression by regulating the turnover or activity of transcription factors or of their inhibitors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7720071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Ono, Y., Shimada, H., Sorimachi, H., Richard, I., Saido, T. C., Beckmann, J. S., Ishiura, S., Suzuki, K. <strong>Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A.</strong> J. Biol. Chem. 273: 17073-17078, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9642272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9642272</a>] [<a href="https://doi.org/10.1074/jbc.273.27.17073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9642272">Ono et al. (1998)</a> constructed 9 CAPN3 missense point mutations and analyzed the unique properties of the resultant protein product. All mutants completely or almost completely lost proteolytic activity against a potential substrate, fodrin. However, some of the mutants still possessed autolytic activity and/or connectin/titin (TTN; <a href="/entry/188840">188840</a>)-binding ability, indicating that these properties are not necessary for the LGMDR1 phenotype. These results provided strong evidence that LGMD2A results from the loss of proteolysis of substrates by p94, suggesting a novel molecular mechanism leading to muscular dystrophies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9642272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Zatz, M., Starling, A. <strong>Calpains and disease.</strong> New Eng. J. Med. 352: 2413-2423, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15944426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15944426</a>] [<a href="https://doi.org/10.1056/NEJMra043361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15944426">Zatz and Starling (2005)</a> reviewed the roles of calpains in disease with specific reference to the etiologic role of mutations in CAPN3 in LGMD2A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15944426" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In many patients with LGMDR1, loss-of-function mutations cause enzymatic inactivation of calpain-3 while protein quantity remains normal. Because the diagnosis of calpainopathy is obtained by identifying calpain-3 protein deficiency or mutations in the CAPN3 gene, the identification of such patients is difficult. <a href="#4" class="mim-tip-reference" title="Fanin, M., Nascimbeni, A. C., Angelini, C. <strong>Screening of calpain-3 autolytic activity in LGMD muscle: a functional map of CAPN3 gene mutations.</strong> J. Med. Genet. 44: 38-43, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16971480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16971480</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16971480[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmg.2006.044859" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16971480">Fanin et al. (2007)</a> used a functional in vitro assay to test calpain-3 autolytic function in a large series of muscle biopsy specimens from patients with unclassified LGMD/hyperCKemia who had been shown to have normal calpain-3 protein quantity. Of 148 muscle biopsy specimens tested, 17 (11%) had lost normal autolytic function. The CAPN3 gene mutations were identified in 15 of the 17 patients (88%), who accounted for about 20% of the total patients with LGMDR1 diagnosed in their series. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16971480" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Autosomal Dominant Limb-Girdle Muscular Dystrophy 4</em></strong></p><p>
|
|
In 36 patients from 10 families of northern European descent with autosomal dominant limb-girdle muscular dystrophy-4 (LGMDD4; <a href="/entry/618129">618129</a>), earlier designated LGMD1I, <a href="#26" class="mim-tip-reference" title="Vissing, J., Barresi, R., Witting, N., Van Ghelue, M., Gammelgaard, L., Bindoff, L. A., Straub, V., Lochmuller, H., Hudson, J., Wahl, C. M., Arnardottir, S., Dahlbom, K., Jonsrud, C., Duno, M. <strong>A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy.</strong> Brain 139: 2154-2163, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27259757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27259757</a>] [<a href="https://doi.org/10.1093/brain/aww133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27259757">Vissing et al. (2016)</a> identified a heterozygous in-frame 21-bp deletion in the CAPN3 gene (c.643_663del21; <a href="#0011">114240.0011</a>). Haplotype analysis of 4 families indicated a founder effect. Analysis of several patients' muscle tissue showed normal mRNA levels and no evidence of nonsense-mediated mRNA decay, but significantly decreased CAPN3 protein levels, at less than 15% of control values. <a href="#26" class="mim-tip-reference" title="Vissing, J., Barresi, R., Witting, N., Van Ghelue, M., Gammelgaard, L., Bindoff, L. A., Straub, V., Lochmuller, H., Hudson, J., Wahl, C. M., Arnardottir, S., Dahlbom, K., Jonsrud, C., Duno, M. <strong>A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy.</strong> Brain 139: 2154-2163, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27259757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27259757</a>] [<a href="https://doi.org/10.1093/brain/aww133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27259757">Vissing et al. (2016)</a> postulated that the in-frame nature of the mutation may have led to expression of a mutated protein that could have a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27259757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 unrelated patients of northern European descent with LGMDD4, <a href="#13" class="mim-tip-reference" title="Martinez-Thompson, J. M., Niu, Z., Tracy, J. A., Moore, S. A., Swenson, A., Wieben, E. D., Milone, M. <strong>Autosomal dominant calpainopathy due to heterozygous CAPN3 c.643_663del21.</strong> Muscle Nerve. 57: 679-683, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28881388/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28881388</a>] [<a href="https://doi.org/10.1002/mus.25970" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28881388">Martinez-Thompson et al. (2018)</a> identified the same heterozygous 21-bp deletion in the CAPN3 gene that had been reported by <a href="#26" class="mim-tip-reference" title="Vissing, J., Barresi, R., Witting, N., Van Ghelue, M., Gammelgaard, L., Bindoff, L. A., Straub, V., Lochmuller, H., Hudson, J., Wahl, C. M., Arnardottir, S., Dahlbom, K., Jonsrud, C., Duno, M. <strong>A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy.</strong> Brain 139: 2154-2163, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27259757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27259757</a>] [<a href="https://doi.org/10.1093/brain/aww133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27259757">Vissing et al. (2016)</a>. The deletion resulted in the deletion of residues Ser215_Gly221 in the first structural domain. Functional studies of the variant were not performed, but Western blot analysis of patient tissues showed greatly decreased amounts of CAPN3 protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=28881388+27259757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#23" class="mim-tip-reference" title="Tagawa, K., Taya, C., Hayashi, Y., Nakagawa, M., Ono, Y., Fukuda, R., Karasuyama, H., Toyama-Sorimachi, N., Katsui, Y., Hata, S., Ishiura, S., Nonaka, I., Seyama, Y., Arahata, K., Yonekawa, H., Sorimachi, H., Suzuki, K. <strong>Myopathy phenotype of transgenic mice expressing active site-mutated inactive p94 skeletal muscle-specific calpain, the gene product responsible for limb girdle muscular dystrophy type 2A.</strong> Hum. Molec. Genet. 9: 1393-1402, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10814721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10814721</a>] [<a href="https://doi.org/10.1093/hmg/9.9.1393" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10814721">Tagawa et al. (2000)</a> created transgenic mice that expressed an inactive mutant of p94, in which the active site cys129 is replaced by ser (p94:C129S). Transgenic mice expressing p94:C129S mRNA showed significantly decreased grip strength. Sections of soleus and extensor digitorum longus (EDL) muscles of the aged transgenic mice showed increased numbers of lobulated and split fibers, respectively, which are often observed in limb-girdle muscular dystrophy muscles. Centrally placed nuclei were also frequently found in the EDL muscle of the transgenic mice, whereas wildtype mice of the same age had almost none. More p94 protein was produced in aged transgenic mice muscles, and the protein showed significantly less autolytic degradation activity than that in wildtype mice. The authors hypothesized that accumulation of p94:C129S protein caused these myopathy phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10814721" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The giant protein titin (<a href="/entry/188840">188840</a>) serves a primary role as a scaffold for sarcomere assembly; one potential mediator of this process is calpain-3. To test the hypothesis that calpain-3 mediates remodeling during myofibrillogenesis, <a href="#10" class="mim-tip-reference" title="Kramerova, I., Kudryashova, E., Tidball, J. G., Spencer, M. J. <strong>Null mutation of calpain 3 (p94) in mice causes abnormal sarcomere formation in vivo and in vitro.</strong> Hum. Molec. Genet. 13: 1373-1388, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15138196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15138196</a>] [<a href="https://doi.org/10.1093/hmg/ddh153" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15138196">Kramerova et al. (2004)</a> generated Capn3-knockout (C3KO) mice. The mice were atrophic, with small foci of muscular necrosis. Myogenic cells fused normally in vitro, but lacked well-organized sarcomeres, as visualized by electron microscopy. Titin distribution was normal in longitudinal sections from the C3KO mice; however, electron microscopy of muscle fibers showed misaligned A-bands. In vitro studies revealed that calpain-3 can bind and cleave titin and that some mutations that are pathogenic in human muscular dystrophy result in reduced affinity of calpain-3 for titin. <a href="#10" class="mim-tip-reference" title="Kramerova, I., Kudryashova, E., Tidball, J. G., Spencer, M. J. <strong>Null mutation of calpain 3 (p94) in mice causes abnormal sarcomere formation in vivo and in vitro.</strong> Hum. Molec. Genet. 13: 1373-1388, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15138196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15138196</a>] [<a href="https://doi.org/10.1093/hmg/ddh153" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15138196">Kramerova et al. (2004)</a> suggested a role for calpain-3 in myofibrillogenesis and sarcomere remodeling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15138196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Kramerova, I., Kudryashova, E., Venkatraman, G., Spencer, M. J. <strong>Calpain 3 participates in sarcomere remodeling by acting upstream of the ubiquitin-proteasome pathway.</strong> Hum. Molec. Genet. 14: 2125-2134, 2005. Note: Erratum: Hum. Molec. Genet. 16: 1006 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15961411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15961411</a>] [<a href="https://doi.org/10.1093/hmg/ddi217" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15961411">Kramerova et al. (2005)</a> showed that the rates of atrophy and growth were decreased in C3KO mouse muscles under conditions promoting sarcomere remodeling. In wildtype mice, ubiquitinated proteins accumulated during muscle reloading, possibly reflecting removal of atrophy-specific and damaged proteins. The increase in ubiquitination correlated with an increase in calpain-3 expression. There was upregulation of heat shock proteins in C3KO muscles following challenge with a physiologic condition that required highly increased protein degradation. Old C3KO mice showed evidence of insoluble protein aggregate formation in skeletal muscles. <a href="#11" class="mim-tip-reference" title="Kramerova, I., Kudryashova, E., Venkatraman, G., Spencer, M. J. <strong>Calpain 3 participates in sarcomere remodeling by acting upstream of the ubiquitin-proteasome pathway.</strong> Hum. Molec. Genet. 14: 2125-2134, 2005. Note: Erratum: Hum. Molec. Genet. 16: 1006 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15961411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15961411</a>] [<a href="https://doi.org/10.1093/hmg/ddi217" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15961411">Kramerova et al. (2005)</a> suggested that accumulation of aged and damaged proteins may lead to cellular toxicity and a cell stress response in C3KO muscles, and that these characteristics may be pathologic features of LGMDR1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15961411" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Huebsch, K. A., Kudryashova, E., Wooley, C. M., Sher, R. B., Seburn, K. L., Spencer, M. J., Cox, G. A. <strong>Mdm muscular dystrophy: interactions with calpain 3 and a novel functional role for titin's N2A domain.</strong> Hum. Molec. Genet. 14: 2801-2811, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16115818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16115818</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16115818[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddi313" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16115818">Huebsch et al. (2005)</a> generated CAPN3 overexpressing transgenic (C3Tg) and C3KO mice and showed that overexpression of CAPN3 exacerbated mdm disease, leading to a shorter life span and more severe muscular dystrophy. However, C3KO/mdm double-mutant mice showed no change in the progression or severity of disease, indicating that aberrant CAPN3 activity is not a primary mechanism in this disease. The authors examined the treadmill locomotion of heterozygous +/mdm mice and detected a significant increase in stride time with a concomitant increase in stance time. These altered gait parameters were completely corrected by CAPN3 overexpression in C3Tg/+/mdm mice, suggesting a CAPN3-dependent role for the N2A domain of TTN in the dynamics of muscle contraction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16115818" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Kramerova, I., Kudryashova, E., Wu, B., Germain, S., Vandenborne, K., Romain, N., Haller, R. G., Verity, M. A., Spencer, M. J. <strong>Mitochondrial abnormalities, energy deficit and oxidative stress are features of calpain 3 deficiency in skeletal muscle.</strong> Hum. Molec. Genet. 18: 3194-3205, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19483197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19483197</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19483197[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp257" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19483197">Kramerova et al. (2009)</a> reported both morphologic and biochemical evidence of mitochondrial abnormalities in C3KO mouse muscles, including irregular ultrastructure and distribution of mitochondria. The morphologic abnormalities in C3KO muscles were associated with reduced in vivo mitochondrial ATP production. Mitochondrial abnormalities in C3KO muscles also correlated with the presence of oxidative stress; increased protein modification by oxygen free radicals and an elevated concentration of the antioxidative enzyme Mn-superoxide dismutase (SOD2; <a href="/entry/147460">147460</a>) were observed in C3KO muscles. The activity of the beta-oxidation enzyme, VLCAD (ACADVL; <a href="/entry/609575">609575</a>), was decreased in C3KO mitochondrial fractions compared with wildtype, suggestive of a general mitochondrial dysfunction. <a href="#12" class="mim-tip-reference" title="Kramerova, I., Kudryashova, E., Wu, B., Germain, S., Vandenborne, K., Romain, N., Haller, R. G., Verity, M. A., Spencer, M. J. <strong>Mitochondrial abnormalities, energy deficit and oxidative stress are features of calpain 3 deficiency in skeletal muscle.</strong> Hum. Molec. Genet. 18: 3194-3205, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19483197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19483197</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19483197[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp257" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19483197">Kramerova et al. (2009)</a> suggested that mitochondrial abnormalities leading to oxidative stress and energy deficit may be important pathologic features of calpainopathy and possibly represent secondary effects of the absence of calpain-3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19483197" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="allelicVariants" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<span href="#mimAllelicVariantsFold" id="mimAllelicVariantsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
|
|
</span>
|
|
<strong>11 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/114240" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=114240[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
|
|
|
|
</div>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0001" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CAPN3, ARG769GLN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs80338802 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338802;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs80338802?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80338802" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80338802" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000020096 OR RCV000711017 OR RCV001814000 OR RCV003473106 OR RCV005007872" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000020096, RCV000711017, RCV001814000, RCV003473106, RCV005007872" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000020096...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 10 Amish families from northern Indiana with autosomal recessive limb-girdle muscular dystrophy type 2A (LGMDR1; <a href="/entry/253600">253600</a>), <a href="#20" class="mim-tip-reference" title="Richard, I., Broux, O., Allamand, V., Fougerousse, F., Chiannilkulchai, N., Bourg, N., Brenguier, L., Devaud, C., Pasturaud, P., Roudaut, C., Hillaire, D., Passos-Bueno, M.-R., Zatz, M., Tischfield, J. A., Fardeau, M., Jackson, C. E., Cohen, D., Beckmann, J. S. <strong>Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.</strong> Cell 81: 27-40, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7720071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7720071</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90368-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7720071">Richard et al. (1995)</a> identified homozygosity for a 2306G-A transition in exon 22 of the CAPN3 gene, resulting in an arg769-to-gln (R769Q) substitution in domain IV of the protein within the third EF-hand of the helix-loop junction. The substitution occurred in a residue conserved throughout all members of the calpain family in all species. This nucleotide change was not present in patients from the 6 southern Indiana Amish LGMD families for which the chromosome 15 locus was excluded by linkage analysis, thus confirming the genetic heterogeneity of this disease in the Amish. The slowly progressive muscle weakness was usually first evident in the pelvic girdle, and then spread to the upper limbs while sparing facial muscles. Unlike the findings in Reunion Islanders, the disorder in the northern Indiana Amish appeared to be fully penetrant, and <a href="#20" class="mim-tip-reference" title="Richard, I., Broux, O., Allamand, V., Fougerousse, F., Chiannilkulchai, N., Bourg, N., Brenguier, L., Devaud, C., Pasturaud, P., Roudaut, C., Hillaire, D., Passos-Bueno, M.-R., Zatz, M., Tischfield, J. A., Fardeau, M., Jackson, C. E., Cohen, D., Beckmann, J. S. <strong>Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.</strong> Cell 81: 27-40, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7720071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7720071</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90368-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7720071">Richard et al. (1995)</a> suggested a digenic model with a second locus to account for this inheritance pattern. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7720071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The same R769Q mutation was found by <a href="#20" class="mim-tip-reference" title="Richard, I., Broux, O., Allamand, V., Fougerousse, F., Chiannilkulchai, N., Bourg, N., Brenguier, L., Devaud, C., Pasturaud, P., Roudaut, C., Hillaire, D., Passos-Bueno, M.-R., Zatz, M., Tischfield, J. A., Fardeau, M., Jackson, C. E., Cohen, D., Beckmann, J. S. <strong>Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.</strong> Cell 81: 27-40, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7720071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7720071</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90368-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7720071">Richard et al. (1995)</a> in affected members of a Brazilian family; the mutation was within a completely different haplotype from that observed in the Amish families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7720071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Pratt, V. M., Jackson, C. E., Wallace, D. C., Gurley, D. S., Feit, A., Feldman, G. L. <strong>DNA studies of limb-girdle muscular dystrophy type 2A in the Amish exclude a modifying mitochondrial gene and show no evidence for a modifying nuclear gene. (Letter)</strong> Am. J. Hum. Genet. 61: 231-233, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9246005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9246005</a>] [<a href="https://doi.org/10.1016/S0002-9297(07)64296-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9246005">Pratt et al. (1997)</a> found no phenotypically normal R769Q homozygotes among 580 DNA samples from Amish individuals in a northern Indiana county. In addition, mitochondrial studies gave no evidence of a modifying mitochondrial gene. These findings argued against possible digenic inheritance postulated by <a href="#20" class="mim-tip-reference" title="Richard, I., Broux, O., Allamand, V., Fougerousse, F., Chiannilkulchai, N., Bourg, N., Brenguier, L., Devaud, C., Pasturaud, P., Roudaut, C., Hillaire, D., Passos-Bueno, M.-R., Zatz, M., Tischfield, J. A., Fardeau, M., Jackson, C. E., Cohen, D., Beckmann, J. S. <strong>Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.</strong> Cell 81: 27-40, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7720071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7720071</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90368-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7720071">Richard et al. (1995)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9246005+7720071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0002" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CAPN3, ARG572GLN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121434544 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434544;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121434544?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121434544" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121434544" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019180 OR RCV000726518 OR RCV001198825 OR RCV003323362" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019180, RCV000726518, RCV001198825, RCV003323362" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019180...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In members of a family from Reunion Island who had limb-girdle muscular dystrophy type 2A (LGMDR1; <a href="/entry/253600">253600</a>), <a href="#20" class="mim-tip-reference" title="Richard, I., Broux, O., Allamand, V., Fougerousse, F., Chiannilkulchai, N., Bourg, N., Brenguier, L., Devaud, C., Pasturaud, P., Roudaut, C., Hillaire, D., Passos-Bueno, M.-R., Zatz, M., Tischfield, J. A., Fardeau, M., Jackson, C. E., Cohen, D., Beckmann, J. S. <strong>Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.</strong> Cell 81: 27-40, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7720071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7720071</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90368-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7720071">Richard et al. (1995)</a> found homozygosity for 1715G-A transition in exon 13 of the CAPN3 gene, resulting in an arg572-to-gln (R572Q) substitution inside domain III. This residue is highly conserved throughout all known calpains. The mutation, detectable by loss of a MspI restriction site, was present only in this family and in no other examined LGMD2A families or unrelated controls. It was 1 of 6 different CAPN3 mutations found in Reunion Island patients, and at least 1 more mutation was predicted from haplotype analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7720071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0003" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CAPN3, ARG110TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121434545 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434545;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121434545?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121434545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121434545" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019181 OR RCV001813749 OR RCV004998102 OR RCV005007873" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019181, RCV001813749, RCV004998102, RCV005007873" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019181...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Brazilian family with limb-girdle muscular dystrophy type 2A (LGMDR1; <a href="/entry/253600">253600</a>), <a href="#20" class="mim-tip-reference" title="Richard, I., Broux, O., Allamand, V., Fougerousse, F., Chiannilkulchai, N., Bourg, N., Brenguier, L., Devaud, C., Pasturaud, P., Roudaut, C., Hillaire, D., Passos-Bueno, M.-R., Zatz, M., Tischfield, J. A., Fardeau, M., Jackson, C. E., Cohen, D., Beckmann, J. S. <strong>Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.</strong> Cell 81: 27-40, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7720071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7720071</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90368-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7720071">Richard et al. (1995)</a> identified a homozygous 328C-T transition in exon 2 of the CAPN3 gene, resulting in an arg110-to-ter (R110X) substitution. The parents were consanguineous. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7720071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0004" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CAPN3, SER86PHE
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121434546 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434546;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121434546?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121434546" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121434546" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019182" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019182" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019182</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In patients with limb-girdle muscular dystrophy type 2A (LGMDR1; <a href="/entry/253600">253600</a>), <a href="#19" class="mim-tip-reference" title="Richard, I., Brenguier, L., Dincer, P., Roudaut, C., Bady, B., Burgunder, J.-M., Chemaly, R., Garcia, C. A., Halaby, G., Jackson, C. E., Kurnit, D. M., Lefranc, G., Legum, C., Loiselet, J., Merlini, L., Nivelon-Chevallier, A., Ollagnon-Roman, E., Restagno, G., Topaloglu, H., Beckmann, J. S. <strong>Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins.</strong> Am. J. Hum. Genet. 60: 1128-1138, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9150160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9150160</a>]" pmid="9150160">Richard et al. (1997)</a> described a ser86-to-phe (S86F) mutation in the CAPN3 gene. Patients who were homozygous for this mutation had disease onset at age 6 to 7 years and presented with severe weakness in their lower limbs, leading to loss of mobility less than 8 years after onset. In contrast, their cousins who were compound heterozygotes for the S86F and P319L (<a href="#0005">114240.0005</a>) mutations were comparatively mildly affected, with disease onset at age 15 to 17 years on average, and with loss of mobility at age 32 years for 1 of them, whereas the 2 others were still walking at ages 29 years and 28 years. All healthy heterozygotes carrying the S86F mutation had mildly elevated creatine kinase (CK) levels. This observation suggested that the mutation affects muscle cells in a somewhat dominant manner. In this kindred, 2 patients belonging to different branches of the family were diagnosed independently with polymyositis. A muscle biopsy of 1 of them showed minimal abnormalities at the limits of significance. Both patients were treated with steroids for an extended period. Eventually, family history led to a consideration of the diagnosis of muscular dystrophy. Only the identification of the pathogenic mutation allowed the definitive diagnosis of LGMD2A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9150160" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0005" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CAPN3, PRO319LEU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121434547 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434547;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121434547?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121434547" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121434547" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019183 OR RCV000417420 OR RCV003473107 OR RCV005007874" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019183, RCV000417420, RCV003473107, RCV005007874" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019183...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the pro319-to-leu (P319L) mutation in the CAPN3 gene that was found in compound heterozygous state in patients with limb-girdle muscular dystrophy type 2A (LGMDR1; <a href="/entry/253600">253600</a>) by <a href="#19" class="mim-tip-reference" title="Richard, I., Brenguier, L., Dincer, P., Roudaut, C., Bady, B., Burgunder, J.-M., Chemaly, R., Garcia, C. A., Halaby, G., Jackson, C. E., Kurnit, D. M., Lefranc, G., Legum, C., Loiselet, J., Merlini, L., Nivelon-Chevallier, A., Ollagnon-Roman, E., Restagno, G., Topaloglu, H., Beckmann, J. S. <strong>Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins.</strong> Am. J. Hum. Genet. 60: 1128-1138, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9150160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9150160</a>]" pmid="9150160">Richard et al. (1997)</a>, see <a href="#0004">114240.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9150160" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0006" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MYOSITIS, EOSINOPHILIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CAPN3, 2362AG-TCATCT
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1555423217 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555423217;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1555423217" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1555423217" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs80338804 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338804;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs80338804?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80338804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80338804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019184 OR RCV000019185 OR RCV000294609 OR RCV002490390 OR RCV003114199 OR RCV003473108" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019184, RCV000019185, RCV000294609, RCV002490390, RCV003114199, RCV003473108" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019184...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In Guipuzcoa, a small mountainous Basque province in northern Spain, <a href="#25" class="mim-tip-reference" title="Urtasun, M., Saenz, A., Roudaut, C., Poza, J. J., Urtizberea, J. A., Cobo, A. M., Richard, I., Garcia Bragado, F., Leturcq, F., Kaplan, J. C., Marti Masso, J. F., Beckmann, J. S., Lopez de Munain, A. <strong>Limb-girdle muscular dystrophy in Guipuzcoa (Basque Country, Spain).</strong> Brain 121: 1735-1747, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9762961/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9762961</a>] [<a href="https://doi.org/10.1093/brain/121.9.1735" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9762961">Urtasun et al. (1998)</a> found the highest prevalence rate of limb-girdle muscular dystrophy described to that time: 69 per million. In 28 families with 38 individuals who had autosomal recessive limb-girdle muscular dystrophy type 2A (LGMDR1; <a href="/entry/253600">253600</a>), mutations in the CAPN3 gene were identified. The predominant Basque mutation was a frameshift in exon 22 (2362AG-to-TCATCT). This mutation was carried by 2 different haplotypes, which were thought to have been derived from a single ancestral founder haplotype by microsatellite mutation. The common Basque frameshift mutation had previously been identified in 1 Brazilian, 1 French, and 1 American family (<a href="#19" class="mim-tip-reference" title="Richard, I., Brenguier, L., Dincer, P., Roudaut, C., Bady, B., Burgunder, J.-M., Chemaly, R., Garcia, C. A., Halaby, G., Jackson, C. E., Kurnit, D. M., Lefranc, G., Legum, C., Loiselet, J., Merlini, L., Nivelon-Chevallier, A., Ollagnon-Roman, E., Restagno, G., Topaloglu, H., Beckmann, J. S. <strong>Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins.</strong> Am. J. Hum. Genet. 60: 1128-1138, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9150160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9150160</a>]" pmid="9150160">Richard et al., 1997</a>). Since their data suggested a founder effect for this frameshift mutation in the Basque population, and because the families with the mutation described by <a href="#19" class="mim-tip-reference" title="Richard, I., Brenguier, L., Dincer, P., Roudaut, C., Bady, B., Burgunder, J.-M., Chemaly, R., Garcia, C. A., Halaby, G., Jackson, C. E., Kurnit, D. M., Lefranc, G., Legum, C., Loiselet, J., Merlini, L., Nivelon-Chevallier, A., Ollagnon-Roman, E., Restagno, G., Topaloglu, H., Beckmann, J. S. <strong>Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins.</strong> Am. J. Hum. Genet. 60: 1128-1138, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9150160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9150160</a>]" pmid="9150160">Richard et al. (1997)</a> shared the same haplotype, <a href="#25" class="mim-tip-reference" title="Urtasun, M., Saenz, A., Roudaut, C., Poza, J. J., Urtizberea, J. A., Cobo, A. M., Richard, I., Garcia Bragado, F., Leturcq, F., Kaplan, J. C., Marti Masso, J. F., Beckmann, J. S., Lopez de Munain, A. <strong>Limb-girdle muscular dystrophy in Guipuzcoa (Basque Country, Spain).</strong> Brain 121: 1735-1747, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9762961/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9762961</a>] [<a href="https://doi.org/10.1093/brain/121.9.1735" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9762961">Urtasun et al. (1998)</a> speculated on a Basque origin for this mutation, which could have moved to Brazil, America, and Reunion by immigration. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9762961+9150160" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Krahn, M., Lopez de Munain, A., Streichenberger, N., Bernard, R., Pecheux, C., Testard, H., Pena-Segura, J. L., Yoldi, E., Cabello, A., Romero, N. B., Poza, J. J., Bouillot-Eimer, S., Ferrer, X., Goicoechea, M., Garcia-Bragado, F., Leturcq, F., Urtizberea, J. A., Levy, N. <strong>CAPN3 mutations in patients with idiopathic eosinophilic myositis.</strong> Ann. Neurol. 59: 905-911, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16607617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16607617</a>] [<a href="https://doi.org/10.1002/ana.20833" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16607617">Krahn et al. (2006)</a> reported 3 unrelated patients with the CAPN3 Basque mutation who were originally diagnosed with eosinophilic myositis (see <a href="/entry/253600">253600</a>) based on skeletal muscle biopsy in the first decade of life. All patients presented initially with increased serum creatine kinase. Skeletal muscle biopsies showed focal inflammatory lesions with eosinophilic infiltration and necrotic muscle fibers with no evidence of parasites. Clinically, the patients had muscle weakness and difficulty walking that increased with age. <a href="#9" class="mim-tip-reference" title="Krahn, M., Lopez de Munain, A., Streichenberger, N., Bernard, R., Pecheux, C., Testard, H., Pena-Segura, J. L., Yoldi, E., Cabello, A., Romero, N. B., Poza, J. J., Bouillot-Eimer, S., Ferrer, X., Goicoechea, M., Garcia-Bragado, F., Leturcq, F., Urtizberea, J. A., Levy, N. <strong>CAPN3 mutations in patients with idiopathic eosinophilic myositis.</strong> Ann. Neurol. 59: 905-911, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16607617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16607617</a>] [<a href="https://doi.org/10.1002/ana.20833" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16607617">Krahn et al. (2006)</a> suggested that eosinophilic myositis may be an early and transient feature in calpainopathies, because it was not present in biopsies from older patients with typical LGMD2A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16607617" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0007" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CAPN3, 1080G-C, TRP360CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606703 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606703;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs267606703" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs267606703" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019186" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019186" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019186</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#8" class="mim-tip-reference" title="Kawai, H., Akaike, M., Kunishige, M., Inui, T., Adachi, K., Kimura, C., Kawajiri, M., Nishida, Y., Endo, I., Kashiwagi, S., Nishino, H., Fujiwara, T., Okuno, S., Roudaut, C., Richard, I., Beckmann, J. S., Miyoshi, K., Matsumoto, T. <strong>Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families.</strong> Muscle Nerve 21: 1493-1501, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771675</a>] [<a href="https://doi.org/10.1002/(sici)1097-4598(199811)21:11<1493::aid-mus19>3.0.co;2-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9771675">Kawai et al. (1998)</a> reported on the clinical, pathologic, and genetic features of 7 patients with limb-girdle muscular dystrophy type 2A (LGMDR1; <a href="/entry/253600">253600</a>) from 3 consanguineous Japanese families. The mean age of onset was 9.7 years +/- 3.1 years, and loss of ambulation occurred at 38.5 +/- 2.1 years. Muscle atrophy was predominant in the pelvic and shoulder girdles and proximal limb muscles. In 2 families, an identical 1080G-C transversion was found in the CAPN3 gene; a frameshift mutation (1796insA; <a href="#0008">114240.0008</a>) was found in the third family. The former mutation resulted in a trp360-to-cys (T360C) substitution in the proteolytic site of calpain-3, and the latter in a deletion of the Ca(2+)-binding domain. (In their article, <a href="#8" class="mim-tip-reference" title="Kawai, H., Akaike, M., Kunishige, M., Inui, T., Adachi, K., Kimura, C., Kawajiri, M., Nishida, Y., Endo, I., Kashiwagi, S., Nishino, H., Fujiwara, T., Okuno, S., Roudaut, C., Richard, I., Beckmann, J. S., Miyoshi, K., Matsumoto, T. <strong>Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families.</strong> Muscle Nerve 21: 1493-1501, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771675</a>] [<a href="https://doi.org/10.1002/(sici)1097-4598(199811)21:11<1493::aid-mus19>3.0.co;2-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9771675">Kawai et al. (1998)</a> reported the amino acid substitution as trp360-to-cys in Figure 6 and in the text, but as trp360-to-arg in the abstract.) <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9771675" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0008" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CAPN3, 1-BP INS, 1796A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80338803 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338803;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80338803" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80338803" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019187 OR RCV000518261 OR RCV001814001 OR RCV003473109 OR RCV005007875" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019187, RCV000518261, RCV001814001, RCV003473109, RCV005007875" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019187...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp insertion in the CAPN3 gene (1796insA) that was found in compound heterozygous state in patients with limb-girdle muscular dystrophy type 2A (LGMDR1; <a href="/entry/253600">253600</a>) by <a href="#8" class="mim-tip-reference" title="Kawai, H., Akaike, M., Kunishige, M., Inui, T., Adachi, K., Kimura, C., Kawajiri, M., Nishida, Y., Endo, I., Kashiwagi, S., Nishino, H., Fujiwara, T., Okuno, S., Roudaut, C., Richard, I., Beckmann, J. S., Miyoshi, K., Matsumoto, T. <strong>Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families.</strong> Muscle Nerve 21: 1493-1501, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771675</a>] [<a href="https://doi.org/10.1002/(sici)1097-4598(199811)21:11<1493::aid-mus19>3.0.co;2-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9771675">Kawai et al. (1998)</a>, see <a href="#0007">114240.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9771675" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0009" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CAPN3, 1-BP DEL, 550A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs80338800 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338800;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs80338800?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80338800" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80338800" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019188 OR RCV000078099 OR RCV000348995 OR RCV000414969 OR RCV000415100 OR RCV000415344 OR RCV000415373 OR RCV000626574 OR RCV000626575 OR RCV000626576 OR RCV000626577 OR RCV001197255 OR RCV001420332 OR RCV001849271 OR RCV002496413 OR RCV004998103" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019188, RCV000078099, RCV000348995, RCV000414969, RCV000415100, RCV000415344, RCV000415373, RCV000626574, RCV000626575, RCV000626576, RCV000626577, RCV001197255, RCV001420332, RCV001849271, RCV002496413, RCV004998103" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019188...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In Croatian patients with autosomal recessive limb-girdle muscular dystrophy type 2A (LGMDR1; <a href="/entry/253600">253600</a>), <a href="#2" class="mim-tip-reference" title="Canki-Klain, N., Milic, A., Kovac, B., Trlaja, A., Grgicevic, D., Zurak, N., Fardeau, M., Leturcq, F., Kaplan, J.-C., Urtizberea, J. A., Politano, L., Piluso, G., Feingold, J. <strong>Prevalence of the 550delA mutation in calpainopathy (LGMD 2A) in Croatia.</strong> Am. J. Med. Genet. 125A: 152-156, 2004. Note: Erratum: Am. J. Med. Genet. 130A: 218 only, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14981715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14981715</a>] [<a href="https://doi.org/10.1002/ajmg.a.20408" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14981715">Canki-Klain et al. (2004)</a> identified a 1-bp deletion (550delA) in exon 4 of the CAPN3 gene that was the most common mutation, with a prevalence of 76% of mutant CAPN3 alleles. The detection of 4 healthy 550delA heterozygous individuals yielded a frequency of 1 in 133 (0.75%) in the general Croatian population. All 4 carriers originated from an island and mountain region near the Adriatic, indicating a probable founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14981715" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Fanin, M., Nascimbeni, A. C., Fulizio, L., Angelini, C. <strong>The frequency of limb girdle muscular dystrophy 2A in northeastern Italy.</strong> Neuromusc. Disord. 15: 218-224, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15725583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15725583</a>] [<a href="https://doi.org/10.1016/j.nmd.2004.11.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15725583">Fanin et al. (2005)</a> identified the 550delA mutation in several patients with LGMD from northeastern Italy. The mutation occurred in both the homozygous state and in compound heterozygosity with another CAPN3 mutation. The 550delA mutation accounted for 9 (40%) of 23 mutant CAPN3 alleles from patients specifically from the Friuli region, and haplotype analysis indicated a founder effect. <a href="#5" class="mim-tip-reference" title="Fanin, M., Nascimbeni, A. C., Fulizio, L., Angelini, C. <strong>The frequency of limb girdle muscular dystrophy 2A in northeastern Italy.</strong> Neuromusc. Disord. 15: 218-224, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15725583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15725583</a>] [<a href="https://doi.org/10.1016/j.nmd.2004.11.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15725583">Fanin et al. (2005)</a> concluded that LGMDR1 may be the most frequent autosomal recessive neuromuscular disorder in this region of Italy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15725583" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Todorova, A., Georgieva, B., Tournev, I., Todorov, T., Bogdanova, N., Mitev, V., Mueller, C. R., Kremensky, I., Horst, J. <strong>A large deletion and novel point mutations in the calpain 3 gene (CAPN3) in Bulgarian LGMD2A patients.</strong> Neurogenetics 8: 225-229, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17318636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17318636</a>] [<a href="https://doi.org/10.1007/s10048-007-0083-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17318636">Todorova et al. (2007)</a> identified mutations in the CAPN3 gene in 20 (42%) of 48 unrelated Bulgarian patients with muscular dystrophy. Forty percent of the patients were homozygous for the 500delA mutation, and 70% carried it on at least 1 allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17318636" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0010" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CAPN3, ARG490GLN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121434548 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434548;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121434548?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121434548" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs121434548" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000019189 OR RCV000724646 OR RCV002222356 OR RCV002490391 OR RCV003473110" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000019189, RCV000724646, RCV002222356, RCV002490391, RCV003473110" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000019189...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In several patients with autosomal recessive limb-girdle muscular dystrophy type 2A (LGMDR1; <a href="/entry/253600">253600</a>) from 3 unrelated families in northeastern Italy, <a href="#5" class="mim-tip-reference" title="Fanin, M., Nascimbeni, A. C., Fulizio, L., Angelini, C. <strong>The frequency of limb girdle muscular dystrophy 2A in northeastern Italy.</strong> Neuromusc. Disord. 15: 218-224, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15725583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15725583</a>] [<a href="https://doi.org/10.1016/j.nmd.2004.11.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15725583">Fanin et al. (2005)</a> identified a homozygous arg490-to-gln (R490Q) mutation in the CAPN3 gene. Another patient was compound heterozygous for the R490Q mutation and 550delA (<a href="#0009">114240.0009</a>). The R490Q mutation accounted for 6 (46%) of 13 mutant CAPN3 alleles from patients specifically from the Venezia district, and haplotype analysis indicated a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15725583" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0011" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL DOMINANT 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CAPN3, 21-BP DEL, NT643
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs863224965 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs863224965;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs863224965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs863224965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000201156 OR RCV000379696 OR RCV000681607 OR RCV004998418" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000201156, RCV000379696, RCV000681607, RCV004998418" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000201156...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 36 patients from 10 families of northern European descent with autosomal dominant limb-girdle muscular dystrophy type 1I (LGMDD4; <a href="/entry/618129">618129</a>), <a href="#26" class="mim-tip-reference" title="Vissing, J., Barresi, R., Witting, N., Van Ghelue, M., Gammelgaard, L., Bindoff, L. A., Straub, V., Lochmuller, H., Hudson, J., Wahl, C. M., Arnardottir, S., Dahlbom, K., Jonsrud, C., Duno, M. <strong>A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy.</strong> Brain 139: 2154-2163, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27259757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27259757</a>] [<a href="https://doi.org/10.1093/brain/aww133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27259757">Vissing et al. (2016)</a> identified a heterozygous in-frame 21-bp deletion (c.643_663del21, NM_000070) in the CAPN3 gene. The variant is present at an allele frequency of 0.006% among individuals of European descent in the ExAC database. Haplotype analysis of 4 families indicated a founder effect. Analysis of several patients' muscle tissue showed normal mRNA levels and no evidence of nonsense-mediated mRNA decay, but significantly decreased CAPN3 protein levels, at less than 15% of control values. <a href="#26" class="mim-tip-reference" title="Vissing, J., Barresi, R., Witting, N., Van Ghelue, M., Gammelgaard, L., Bindoff, L. A., Straub, V., Lochmuller, H., Hudson, J., Wahl, C. M., Arnardottir, S., Dahlbom, K., Jonsrud, C., Duno, M. <strong>A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy.</strong> Brain 139: 2154-2163, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27259757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27259757</a>] [<a href="https://doi.org/10.1093/brain/aww133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27259757">Vissing et al. (2016)</a> postulated that the in-frame nature of the mutation may have led to expression of a mutated protein that could have a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27259757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 unrelated patients of northern European descent with LGMDD4, <a href="#13" class="mim-tip-reference" title="Martinez-Thompson, J. M., Niu, Z., Tracy, J. A., Moore, S. A., Swenson, A., Wieben, E. D., Milone, M. <strong>Autosomal dominant calpainopathy due to heterozygous CAPN3 c.643_663del21.</strong> Muscle Nerve. 57: 679-683, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28881388/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28881388</a>] [<a href="https://doi.org/10.1002/mus.25970" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28881388">Martinez-Thompson et al. (2018)</a> identified the same heterozygous 21-bp deletion in the CAPN3 gene that had been reported by <a href="#26" class="mim-tip-reference" title="Vissing, J., Barresi, R., Witting, N., Van Ghelue, M., Gammelgaard, L., Bindoff, L. A., Straub, V., Lochmuller, H., Hudson, J., Wahl, C. M., Arnardottir, S., Dahlbom, K., Jonsrud, C., Duno, M. <strong>A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy.</strong> Brain 139: 2154-2163, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27259757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27259757</a>] [<a href="https://doi.org/10.1093/brain/aww133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27259757">Vissing et al. (2016)</a>. The deletion resulted in the deletion of residues Ser215_Gly221 in the first structural domain. The mutations were found by next-generation, whole-exome, or Sanger sequencing; all were confirmed by Sanger sequencing. Each proband had a family history of the disorder, although not all affected family members were available for genetic testing. Functional studies of the variant were not performed, but Western blot analysis of patient tissues showed greatly decreased amounts of the CAPN3 protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=28881388+27259757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Blazquez2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Blazquez, L., Azpitarte, M., Saenz, A., Goicoechea, M., Otaegui, D., Ferrer, X., Illa, I., Gutierrez-Rivas, E., Vilchez, J. J., Lopez de Munain, A.
|
|
<strong>Characterization of novel CAPN3 isoforms in white blood cells: an alternative approach for limb-girdle muscular dystrophy 2A diagnosis.</strong>
|
|
Neurogenetics 9: 173-182, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18563459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18563459</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18563459" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s10048-008-0129-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Canki-Klain2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Canki-Klain, N., Milic, A., Kovac, B., Trlaja, A., Grgicevic, D., Zurak, N., Fardeau, M., Leturcq, F., Kaplan, J.-C., Urtizberea, J. A., Politano, L., Piluso, G., Feingold, J.
|
|
<strong>Prevalence of the 550delA mutation in calpainopathy (LGMD 2A) in Croatia.</strong>
|
|
Am. J. Med. Genet. 125A: 152-156, 2004. Note: Erratum: Am. J. Med. Genet. 130A: 218 only, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14981715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14981715</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14981715" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.20408" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Duno2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Duno, M., Sveen, M.-L., Schwartz, M., Vissing, J.
|
|
<strong>cDNA analyses of CAPN3 enhances mutation detection and reveals a low prevalence of LGMD2A patients in Denmark.</strong>
|
|
Europ. J. Hum. Genet. 16: 935-940, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18337726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18337726</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18337726" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ejhg.2008.47" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Fanin2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fanin, M., Nascimbeni, A. C., Angelini, C.
|
|
<strong>Screening of calpain-3 autolytic activity in LGMD muscle: a functional map of CAPN3 gene mutations.</strong>
|
|
J. Med. Genet. 44: 38-43, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16971480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16971480</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16971480[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16971480" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2006.044859" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Fanin2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fanin, M., Nascimbeni, A. C., Fulizio, L., Angelini, C.
|
|
<strong>The frequency of limb girdle muscular dystrophy 2A in northeastern Italy.</strong>
|
|
Neuromusc. Disord. 15: 218-224, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15725583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15725583</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15725583" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.nmd.2004.11.003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Huang2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Huang, Y., de Morree, A., van Remoortere, A., Bushby, K., Frants, R. R., Dunnen, J. T., van der Maarel, S.
|
|
<strong>Calpain 3 is a modulator of the dysferlin protein complex in skeletal muscle.</strong>
|
|
Hum. Molec. Genet. 17: 1855-1866, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18334579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18334579</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18334579[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18334579" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddn081" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Huebsch2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Huebsch, K. A., Kudryashova, E., Wooley, C. M., Sher, R. B., Seburn, K. L., Spencer, M. J., Cox, G. A.
|
|
<strong>Mdm muscular dystrophy: interactions with calpain 3 and a novel functional role for titin's N2A domain.</strong>
|
|
Hum. Molec. Genet. 14: 2801-2811, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16115818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16115818</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16115818[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16115818" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddi313" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Kawai1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kawai, H., Akaike, M., Kunishige, M., Inui, T., Adachi, K., Kimura, C., Kawajiri, M., Nishida, Y., Endo, I., Kashiwagi, S., Nishino, H., Fujiwara, T., Okuno, S., Roudaut, C., Richard, I., Beckmann, J. S., Miyoshi, K., Matsumoto, T.
|
|
<strong>Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families.</strong>
|
|
Muscle Nerve 21: 1493-1501, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771675</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9771675" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(sici)1097-4598(199811)21:11<1493::aid-mus19>3.0.co;2-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Krahn2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Krahn, M., Lopez de Munain, A., Streichenberger, N., Bernard, R., Pecheux, C., Testard, H., Pena-Segura, J. L., Yoldi, E., Cabello, A., Romero, N. B., Poza, J. J., Bouillot-Eimer, S., Ferrer, X., Goicoechea, M., Garcia-Bragado, F., Leturcq, F., Urtizberea, J. A., Levy, N.
|
|
<strong>CAPN3 mutations in patients with idiopathic eosinophilic myositis.</strong>
|
|
Ann. Neurol. 59: 905-911, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16607617/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16607617</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16607617" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ana.20833" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Kramerova2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kramerova, I., Kudryashova, E., Tidball, J. G., Spencer, M. J.
|
|
<strong>Null mutation of calpain 3 (p94) in mice causes abnormal sarcomere formation in vivo and in vitro.</strong>
|
|
Hum. Molec. Genet. 13: 1373-1388, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15138196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15138196</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15138196" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddh153" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Kramerova2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kramerova, I., Kudryashova, E., Venkatraman, G., Spencer, M. J.
|
|
<strong>Calpain 3 participates in sarcomere remodeling by acting upstream of the ubiquitin-proteasome pathway.</strong>
|
|
Hum. Molec. Genet. 14: 2125-2134, 2005. Note: Erratum: Hum. Molec. Genet. 16: 1006 only, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15961411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15961411</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15961411" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddi217" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Kramerova2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kramerova, I., Kudryashova, E., Wu, B., Germain, S., Vandenborne, K., Romain, N., Haller, R. G., Verity, M. A., Spencer, M. J.
|
|
<strong>Mitochondrial abnormalities, energy deficit and oxidative stress are features of calpain 3 deficiency in skeletal muscle.</strong>
|
|
Hum. Molec. Genet. 18: 3194-3205, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19483197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19483197</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19483197[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19483197" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddp257" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Martinez-Thompson2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Martinez-Thompson, J. M., Niu, Z., Tracy, J. A., Moore, S. A., Swenson, A., Wieben, E. D., Milone, M.
|
|
<strong>Autosomal dominant calpainopathy due to heterozygous CAPN3 c.643_663del21.</strong>
|
|
Muscle Nerve. 57: 679-683, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28881388/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28881388</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28881388" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/mus.25970" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Ohno1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ohno, S., Minoshima, S., Kudoh, J., Fukuyama, R., Ohmi-Imajoh, S., Suzuki, K., Shimizu, Y., Shimizu, N.
|
|
<strong>Four genes for the calpain family locate on four distinct human chromosomes.</strong>
|
|
Cytogenet. Cell Genet. 53: 225-229, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2209092/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2209092</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2209092" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000132937" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Ono1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ono, Y., Shimada, H., Sorimachi, H., Richard, I., Saido, T. C., Beckmann, J. S., Ishiura, S., Suzuki, K.
|
|
<strong>Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A.</strong>
|
|
J. Biol. Chem. 273: 17073-17078, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9642272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9642272</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9642272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.273.27.17073" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Piluso2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Piluso, G., Politano, L., Aurino, S., Fanin, M., Ricci, E., Ventriglia, V. M., Belsito, A., Totaro, A., Saccone, V., Topaloglu, H., Nascimbeni, A. C., Fulizio, L., Broccolini, A., Canki-Klain, N., Comi, L. I., Nigro, G., Angelini, C., Nigro, V.
|
|
<strong>Extensive scanning of the calpain-3 gene broadens the spectrum of LGMD2A phenotypes.</strong>
|
|
J. Med. Genet. 42: 686-693, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16141003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16141003</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16141003" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2004.028738" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Pratt1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pratt, V. M., Jackson, C. E., Wallace, D. C., Gurley, D. S., Feit, A., Feldman, G. L.
|
|
<strong>DNA studies of limb-girdle muscular dystrophy type 2A in the Amish exclude a modifying mitochondrial gene and show no evidence for a modifying nuclear gene. (Letter)</strong>
|
|
Am. J. Hum. Genet. 61: 231-233, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9246005/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9246005</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9246005" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/S0002-9297(07)64296-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Richard1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Richard, I., Beckmann, J. S.
|
|
<strong>Molecular cloning of mouse Canp3, the gene associated with limb-girdle muscular dystrophy 2A in human.</strong>
|
|
Mammalian Genome 7: 377-379, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8661728/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8661728</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8661728" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s003359900108" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Richard1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Richard, I., Brenguier, L., Dincer, P., Roudaut, C., Bady, B., Burgunder, J.-M., Chemaly, R., Garcia, C. A., Halaby, G., Jackson, C. E., Kurnit, D. M., Lefranc, G., Legum, C., Loiselet, J., Merlini, L., Nivelon-Chevallier, A., Ollagnon-Roman, E., Restagno, G., Topaloglu, H., Beckmann, J. S.
|
|
<strong>Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins.</strong>
|
|
Am. J. Hum. Genet. 60: 1128-1138, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9150160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9150160</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9150160" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Richard1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Richard, I., Broux, O., Allamand, V., Fougerousse, F., Chiannilkulchai, N., Bourg, N., Brenguier, L., Devaud, C., Pasturaud, P., Roudaut, C., Hillaire, D., Passos-Bueno, M.-R., Zatz, M., Tischfield, J. A., Fardeau, M., Jackson, C. E., Cohen, D., Beckmann, J. S.
|
|
<strong>Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.</strong>
|
|
Cell 81: 27-40, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7720071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7720071</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7720071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(95)90368-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Sarparanta2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sarparanta, J., Blandin, G., Charton, K., Vihola, A., Marchand, S., Milic, A., Hackman, P., Ehler, E., Richard, I., Udd, B.
|
|
<strong>Interactions with M-band titin and calpain 3 link myospryn (CMYA5) to tibial and limb-girdle muscular dystrophies.</strong>
|
|
J. Biol. Chem. 285: 30304-30315, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20634290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20634290</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20634290" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M110.108720" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Sorimachi1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sorimachi, H., Imajoh-Ohmi, S., Emori, Y., Kawasaki, H., Ohno, S., Minami, Y., Suzuki, K.
|
|
<strong>Molecular cloning of a novel mammalian calcium-dependent protease distinct from both m- and mu-types: specific expression of the mRNA in skeletal muscle.</strong>
|
|
J. Biol. Chem. 264: 20106-20111, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2555341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2555341</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2555341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Tagawa2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tagawa, K., Taya, C., Hayashi, Y., Nakagawa, M., Ono, Y., Fukuda, R., Karasuyama, H., Toyama-Sorimachi, N., Katsui, Y., Hata, S., Ishiura, S., Nonaka, I., Seyama, Y., Arahata, K., Yonekawa, H., Sorimachi, H., Suzuki, K.
|
|
<strong>Myopathy phenotype of transgenic mice expressing active site-mutated inactive p94 skeletal muscle-specific calpain, the gene product responsible for limb girdle muscular dystrophy type 2A.</strong>
|
|
Hum. Molec. Genet. 9: 1393-1402, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10814721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10814721</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10814721" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/9.9.1393" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Todorova2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Todorova, A., Georgieva, B., Tournev, I., Todorov, T., Bogdanova, N., Mitev, V., Mueller, C. R., Kremensky, I., Horst, J.
|
|
<strong>A large deletion and novel point mutations in the calpain 3 gene (CAPN3) in Bulgarian LGMD2A patients.</strong>
|
|
Neurogenetics 8: 225-229, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17318636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17318636</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17318636" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s10048-007-0083-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Urtasun1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Urtasun, M., Saenz, A., Roudaut, C., Poza, J. J., Urtizberea, J. A., Cobo, A. M., Richard, I., Garcia Bragado, F., Leturcq, F., Kaplan, J. C., Marti Masso, J. F., Beckmann, J. S., Lopez de Munain, A.
|
|
<strong>Limb-girdle muscular dystrophy in Guipuzcoa (Basque Country, Spain).</strong>
|
|
Brain 121: 1735-1747, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9762961/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9762961</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9762961" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/brain/121.9.1735" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Vissing2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vissing, J., Barresi, R., Witting, N., Van Ghelue, M., Gammelgaard, L., Bindoff, L. A., Straub, V., Lochmuller, H., Hudson, J., Wahl, C. M., Arnardottir, S., Dahlbom, K., Jonsrud, C., Duno, M.
|
|
<strong>A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy.</strong>
|
|
Brain 139: 2154-2163, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27259757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27259757</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27259757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/brain/aww133" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Zatz2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zatz, M., Starling, A.
|
|
<strong>Calpains and disease.</strong>
|
|
New Eng. J. Med. 352: 2413-2423, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15944426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15944426</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15944426" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMra043361" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 09/20/2018
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Patricia A. Hartz - updated : 2/14/2012<br>George E. Tiller - updated : 7/7/2010<br>Cassandra L. Kniffin - updated : 12/8/2009<br>George E. Tiller - updated : 11/19/2008<br>Cassandra L. Kniffin - reorganized : 11/12/2008<br>Cassandra L. Kniffin - updated : 11/3/2008<br>Cassandra L. Kniffin - updated : 8/19/2008<br>Cassandra L. Kniffin - updated : 9/21/2007<br>Cassandra L. Kniffin - updated : 9/10/2007<br>Cassandra L. Kniffin - updated : 8/21/2007<br>Victor A. McKusick - updated : 2/21/2007<br>George E. Tiller - updated : 9/11/2006<br>Victor A. McKusick - updated : 12/20/2005<br>Victor A. McKusick - updated : 6/24/2005<br>Cassandra L. Kniffin - updated : 4/12/2005<br>George E. Tiller - updated : 8/8/2000<br>Victor A. McKusick - updated : 1/7/2000<br>Victor A. McKusick - updated : 1/5/2000<br>Victor A. McKusick - updated : 8/20/1997<br>Victor A. McKusick - updated : 6/16/1997
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/5/1989
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 09/27/2018
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 09/26/2018<br>carol : 09/25/2018<br>ckniffin : 09/20/2018<br>carol : 08/05/2016<br>carol : 05/21/2015<br>mcolton : 5/19/2015<br>carol : 11/11/2013<br>mgross : 2/17/2012<br>terry : 2/14/2012<br>carol : 7/29/2010<br>wwang : 7/19/2010<br>terry : 7/7/2010<br>wwang : 2/23/2010<br>ckniffin : 2/19/2010<br>wwang : 1/4/2010<br>ckniffin : 12/8/2009<br>wwang : 5/7/2009<br>wwang : 11/19/2008<br>carol : 11/12/2008<br>ckniffin : 11/3/2008<br>wwang : 8/28/2008<br>ckniffin : 8/19/2008<br>wwang : 9/27/2007<br>ckniffin : 9/21/2007<br>wwang : 9/13/2007<br>ckniffin : 9/10/2007<br>wwang : 9/5/2007<br>ckniffin : 8/21/2007<br>alopez : 2/23/2007<br>terry : 2/21/2007<br>alopez : 9/11/2006<br>wwang : 12/28/2005<br>terry : 12/20/2005<br>alopez : 6/27/2005<br>terry : 6/24/2005<br>tkritzer : 4/14/2005<br>ckniffin : 4/12/2005<br>carol : 10/20/2003<br>carol : 10/17/2003<br>alopez : 8/8/2000<br>psherman : 4/10/2000<br>carol : 1/28/2000<br>carol : 1/28/2000<br>alopez : 1/14/2000<br>terry : 1/7/2000<br>carol : 1/5/2000<br>terry : 1/5/2000<br>carol : 4/21/1999<br>mgross : 4/8/1999<br>alopez : 9/16/1998<br>terry : 9/14/1998<br>carol : 8/18/1998<br>carol : 8/18/1998<br>terry : 6/26/1998<br>terry : 8/25/1997<br>terry : 8/20/1997<br>terry : 6/23/1997<br>terry : 6/16/1997<br>jamie : 1/15/1997<br>terry : 1/8/1997<br>mark : 6/14/1996<br>terry : 6/14/1996<br>terry : 6/11/1996<br>mark : 11/17/1995<br>terry : 6/3/1995<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>carol : 12/19/1989<br>ddp : 10/26/1989
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="container visible-print-block">
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
<div class="col-md-8 col-md-offset-1">
|
|
|
|
<div>
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>*</strong> 114240
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
CALPAIN 3; CAPN3
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
CALPAIN, LARGE POLYPEPTIDE L3<br />
|
|
CALPAIN III, LARGE SUBUNIT; CANPL3<br />
|
|
CALCIUM-ACTIVATED NEUTRAL PROTEASE 3, MUSCLE-SPECIFIC, LARGE SUBUNIT; CANP3<br />
|
|
p94
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: CAPN3</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 1279886003, 370474006, 715341003;
|
|
|
|
|
|
<strong>ICD10CM:</strong> G71.032;
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 15q15.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 15:42,359,501-42,412,317 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
15q15.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Muscular dystrophy, limb-girdle, autosomal dominant 4
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
618129
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Muscular dystrophy, limb-girdle, autosomal recessive 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
253600
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The CAPN3 gene encodes calpain-3. The calpains, or calcium-activated neutral proteases (EC 3.4.22.17), are nonlysosomal intracellular cysteine proteases. Mammalian calpains are heterodimers composed of a ubiquitous 80-kD large subunit (e.g., CAPN1, 114220 and CAPN2, 114230) and a common small 30-kD subunit (CAPNS1; 114170). CAPN3 is a muscle-specific large subunit (Sorimachi et al., 1989). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Sorimachi et al. (1989) isolated a clone corresponding to a novel member of the CAPN (symbolized CANP by them) large subunit family from human and rat skeletal muscle cDNA libraries. The deduced protein (p94), corresponding to CAPN3, contains 821 amino acid residues, has a molecular mass of 94 kD, and shows significant sequence homology with other large subunits. The protein could be divided into 4 domains (I to IV) as reported for the CANP large subunit family. Domains II and IV are potential cysteine protease and calcium-binding domains, respectively, and have sequences homologous to the corresponding domains of other CANP large subunits. However, domain I of p94 is significantly different from others. In addition, p94 contains 2 unique sequences of 62 and 77 residues in domains II and III, respectively. In contrast to the ubiquitous expression of other large subunits, Northern blot analysis detected a p94 mRNA in skeletal muscle. </p><p>Richard et al. (1995) identified the CAPN3 gene by positional cloning of a region on chromosome 15q containing the gene for autosomal recessive limb-girdle muscular dystrophy-1 (LGMDR1; 253600). CAPN3 gene was a particularly attractive candidate because of its functional role in muscle. Richard et al. (1995) reported a gene sequence that differed slightly from that reported by Sorimachi et al. (1989). </p><p>Blazquez et al. (2008) identified 4 different CAPN3 mRNA transcripts in human white blood cells. Sequence analysis showed that exon 15 was always absent, whereas exons 6 and 16 could be present or not. There was only 1 transcript detected in muscle. </p><p>Richard and Beckmann (1996) found that the mouse Capn3 gene encodes an mRNA of a size similar to the human CANP3 mRNA. The mouse gene directs the synthesis of an 821-amino acid protein. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Richard et al. (1995) demonstrated that the CAPN3 gene contains 24 exons and extends over 40 kb. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Ohno et al. (1990) mapped the CAPN3 gene to chromosome 15. </p><p>By somatic cell hybridization, Richard and Beckmann (1996) localized the mouse Capn3 gene to either chromosome 2 or chromosome 4. The results did not allow distinction between these 2 chromosomes, since all hybrids carrying mouse chromosome 2 also carried chromosome 4. The fact that isolated murine YACs amplified a sequence tagged site (STS) for the TYRO3 gene (600341), which maps to human chromosome 15, suggested to Richard and Beckmann (1996) that the 2 genes are adjacent in the mouse. Homology between mouse chromosome 2 and human chromosome 15 is well established by a number of examples of synteny; no homology of synteny has been demonstrated between human 15 and mouse 4. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In COS-1 cells, Huang et al. (2008) demonstrated that calpain-3 and AHNAK (103390) colocalize at the I-band near the A-I junction in skeletal muscle, that calpain-3 cleaves AHNAK, and that this cleavage results in decreased levels of AHNAK. Studies of AHNAK fusion protein constructs showed that calpain-3 can cleave AHNAK at 2 sites in the N terminus and 3 sites in the C terminus, but not at the central M region. Cleavage of AHNAK disrupted its binding to dysferlin (DYSF; 603009) and myoferlin (FER1L3; 604603). Skeletal muscle from 4 patients with autosomal recessive LGMD due to CAPN3 mutations (LGMDR1) showed increased levels of AHNAK at the sarcolemma and blood vessels. Huang et al. (2008) concluded that CAPN3 plays a role in the dysferlin protein complex and that disruption of CAPN3 function may affect muscle membrane repair and remodeling. </p><p>Sarparanta et al. (2010) found that C-terminal domains of the muscle-specific protein myospryn (CMYA5; 612193) interacted with calpain-3. Myospryn appeared to stabilize full-length calpain-3 against proteolytic autoactivation, and active calpain-3 used myospryn as a substrate. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Autosomal Recessive Limb-Girdle Muscular Dystrophy 1</em></strong></p><p>
|
|
By a mutation screen in families with autosomal recessive limb-girdle muscular dystrophy-1 (LGMDR1; 253600), earlier designated LGMD2A, Richard et al. (1995) identified biallelic mutations in the CAPN3 gene, including nonsense, splice site, frameshift, and missense mutations (see, e.g., 114240.0001, 114240.0002, and 114240.0003). The mutations segregated with the disorder in the families. Six of the mutations were found within an inbred population on Reunion Island, located in the Indian Ocean, and haplotype analysis suggested the existence of at least 1 more mutation in the group. The occurrence of multiple independent mutations in the isolated population on Reunion Island rather than the finding of an expected founder mutation was referred to as the 'Reunion paradox' by Richard et al. (1995). They suggested that LGMD2A, instead of being a monogenic disorder, might have a more complex inheritance pattern in which expression of calpain mutations is dependent on genetic background, either nuclear or mitochondrial; see INHERITANCE section in 253600. </p><p>Richard et al. (1997) studied 21 LGMD pedigrees of various origins: France, Israel, Lebanon, Switzerland, United States, Italy, and Turkey. Nine of the 23 families showed linkage to chromosome 15, whereas such linkage was excluded in 10 and was inconclusive in 4. A search for CAPN3 mutations uncovered 19 novel mutations in addition to the 16 described previously (see, e.g., 114240.0004; 114240.0005). A survey of clinical features showed great variability. All patients showed elevated serum creatine kinase in a range of 7 to 84 times the upper limit of normal, marked intra- and interfamilial phenotypic variability in age of onset (range 2.5 to 40 years), and loss of ambulation. For example, affected individuals in 1 family presented with a very mild phenotype, with onset at ages 30 and 40 years, and were still ambulatory at ages 54 and 66 years, respectively. In contrast, 2 Lebanese sibs had onset at age 6 years and had loss of independent walking at ages 13 years and 15 years. </p><p>Fanin et al. (2005) identified mutations in the CAPN3 gene in 70 (33%) of 214 patients with limb-girdle muscular dystrophy in Italy. The prevalence of LGMD2A was estimated at 9.47 per million inhabitants in northeastern Italy. Two founder mutations were identified (500delA, 114240.0009; R490Q, 114240.0010). Todorova et al. (2007) identified mutations in the CAPN3 gene in 20 (42%) of 48 unrelated Bulgarian patients with muscular dystrophy. Three novel and 6 recurrent mutations were identified. Forty percent of the patients were homozygous for the 500delA mutation, and 70% carried it on at least 1 allele. </p><p>By high-throughput denaturing HPLC, Piluso et al. (2005) scanned the CAPN3 gene in 530 individuals with different grades of symptoms consistent with LGMD. They found 141 LGMD2A patients carrying 82 different CAPN3 mutations, of which 45 were novel. Females had a more favorable course than males. In 94% of the most severely affected LGMD2A patients, the defect was also discovered in the second allele. CAPN3 mutations were found in 35.1% of patients with classic LGMD phenotypes, 18.4% of atypical patients, and 12.6% of patients with high serum creatine kinase levels. Piluso et al. (2005) broadened the spectrum of LGMD2A phenotypes and set the carrier frequency at 1:103. </p><p>Among 46 European patients suspected to have LGMD2A based on Western blot results, Duno et al. (2008) found that 16 patients had mutations in the CAPN3 gene identified by both direct genomic sequencing and cDNA analysis. Both mutant alleles were demonstrated in 10 patients. A total of 16 mutations were identified, including 5 novel mutations. Only 3 of the genetically confirmed LGMD2A patients were of Danish origin, indicating a 5- to 6-fold lower prevalence in Denmark compared to other European countries. </p><p>Prior to the identification of CAPN3 as the defective gene in LGMDR1, all identified molecular mechanisms in muscular dystrophies had involved structural components of muscle. CAPN3 appears to have a very rapid turnover mediated by autocatalysis, possibly reflecting the need for precise regulation of its activity. Furthermore, CAPN3 shows a nuclear localization, possibly mediated by the nuclear translocation signal in the IS2 region. Richard et al. (1995) favored the idea that the CAPN3 protein is involved in the control of gene expression by regulating the turnover or activity of transcription factors or of their inhibitors. </p><p>Ono et al. (1998) constructed 9 CAPN3 missense point mutations and analyzed the unique properties of the resultant protein product. All mutants completely or almost completely lost proteolytic activity against a potential substrate, fodrin. However, some of the mutants still possessed autolytic activity and/or connectin/titin (TTN; 188840)-binding ability, indicating that these properties are not necessary for the LGMDR1 phenotype. These results provided strong evidence that LGMD2A results from the loss of proteolysis of substrates by p94, suggesting a novel molecular mechanism leading to muscular dystrophies. </p><p>Zatz and Starling (2005) reviewed the roles of calpains in disease with specific reference to the etiologic role of mutations in CAPN3 in LGMD2A. </p><p>In many patients with LGMDR1, loss-of-function mutations cause enzymatic inactivation of calpain-3 while protein quantity remains normal. Because the diagnosis of calpainopathy is obtained by identifying calpain-3 protein deficiency or mutations in the CAPN3 gene, the identification of such patients is difficult. Fanin et al. (2007) used a functional in vitro assay to test calpain-3 autolytic function in a large series of muscle biopsy specimens from patients with unclassified LGMD/hyperCKemia who had been shown to have normal calpain-3 protein quantity. Of 148 muscle biopsy specimens tested, 17 (11%) had lost normal autolytic function. The CAPN3 gene mutations were identified in 15 of the 17 patients (88%), who accounted for about 20% of the total patients with LGMDR1 diagnosed in their series. </p><p><strong><em>Autosomal Dominant Limb-Girdle Muscular Dystrophy 4</em></strong></p><p>
|
|
In 36 patients from 10 families of northern European descent with autosomal dominant limb-girdle muscular dystrophy-4 (LGMDD4; 618129), earlier designated LGMD1I, Vissing et al. (2016) identified a heterozygous in-frame 21-bp deletion in the CAPN3 gene (c.643_663del21; 114240.0011). Haplotype analysis of 4 families indicated a founder effect. Analysis of several patients' muscle tissue showed normal mRNA levels and no evidence of nonsense-mediated mRNA decay, but significantly decreased CAPN3 protein levels, at less than 15% of control values. Vissing et al. (2016) postulated that the in-frame nature of the mutation may have led to expression of a mutated protein that could have a dominant-negative effect. </p><p>In 3 unrelated patients of northern European descent with LGMDD4, Martinez-Thompson et al. (2018) identified the same heterozygous 21-bp deletion in the CAPN3 gene that had been reported by Vissing et al. (2016). The deletion resulted in the deletion of residues Ser215_Gly221 in the first structural domain. Functional studies of the variant were not performed, but Western blot analysis of patient tissues showed greatly decreased amounts of CAPN3 protein. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Tagawa et al. (2000) created transgenic mice that expressed an inactive mutant of p94, in which the active site cys129 is replaced by ser (p94:C129S). Transgenic mice expressing p94:C129S mRNA showed significantly decreased grip strength. Sections of soleus and extensor digitorum longus (EDL) muscles of the aged transgenic mice showed increased numbers of lobulated and split fibers, respectively, which are often observed in limb-girdle muscular dystrophy muscles. Centrally placed nuclei were also frequently found in the EDL muscle of the transgenic mice, whereas wildtype mice of the same age had almost none. More p94 protein was produced in aged transgenic mice muscles, and the protein showed significantly less autolytic degradation activity than that in wildtype mice. The authors hypothesized that accumulation of p94:C129S protein caused these myopathy phenotypes. </p><p>The giant protein titin (188840) serves a primary role as a scaffold for sarcomere assembly; one potential mediator of this process is calpain-3. To test the hypothesis that calpain-3 mediates remodeling during myofibrillogenesis, Kramerova et al. (2004) generated Capn3-knockout (C3KO) mice. The mice were atrophic, with small foci of muscular necrosis. Myogenic cells fused normally in vitro, but lacked well-organized sarcomeres, as visualized by electron microscopy. Titin distribution was normal in longitudinal sections from the C3KO mice; however, electron microscopy of muscle fibers showed misaligned A-bands. In vitro studies revealed that calpain-3 can bind and cleave titin and that some mutations that are pathogenic in human muscular dystrophy result in reduced affinity of calpain-3 for titin. Kramerova et al. (2004) suggested a role for calpain-3 in myofibrillogenesis and sarcomere remodeling. </p><p>Kramerova et al. (2005) showed that the rates of atrophy and growth were decreased in C3KO mouse muscles under conditions promoting sarcomere remodeling. In wildtype mice, ubiquitinated proteins accumulated during muscle reloading, possibly reflecting removal of atrophy-specific and damaged proteins. The increase in ubiquitination correlated with an increase in calpain-3 expression. There was upregulation of heat shock proteins in C3KO muscles following challenge with a physiologic condition that required highly increased protein degradation. Old C3KO mice showed evidence of insoluble protein aggregate formation in skeletal muscles. Kramerova et al. (2005) suggested that accumulation of aged and damaged proteins may lead to cellular toxicity and a cell stress response in C3KO muscles, and that these characteristics may be pathologic features of LGMDR1. </p><p>Huebsch et al. (2005) generated CAPN3 overexpressing transgenic (C3Tg) and C3KO mice and showed that overexpression of CAPN3 exacerbated mdm disease, leading to a shorter life span and more severe muscular dystrophy. However, C3KO/mdm double-mutant mice showed no change in the progression or severity of disease, indicating that aberrant CAPN3 activity is not a primary mechanism in this disease. The authors examined the treadmill locomotion of heterozygous +/mdm mice and detected a significant increase in stride time with a concomitant increase in stance time. These altered gait parameters were completely corrected by CAPN3 overexpression in C3Tg/+/mdm mice, suggesting a CAPN3-dependent role for the N2A domain of TTN in the dynamics of muscle contraction. </p><p>Kramerova et al. (2009) reported both morphologic and biochemical evidence of mitochondrial abnormalities in C3KO mouse muscles, including irregular ultrastructure and distribution of mitochondria. The morphologic abnormalities in C3KO muscles were associated with reduced in vivo mitochondrial ATP production. Mitochondrial abnormalities in C3KO muscles also correlated with the presence of oxidative stress; increased protein modification by oxygen free radicals and an elevated concentration of the antioxidative enzyme Mn-superoxide dismutase (SOD2; 147460) were observed in C3KO muscles. The activity of the beta-oxidation enzyme, VLCAD (ACADVL; 609575), was decreased in C3KO mitochondrial fractions compared with wildtype, suggestive of a general mitochondrial dysfunction. Kramerova et al. (2009) suggested that mitochondrial abnormalities leading to oxidative stress and energy deficit may be important pathologic features of calpainopathy and possibly represent secondary effects of the absence of calpain-3. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>11 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CAPN3, ARG769GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80338802,
|
|
|
|
|
|
gnomAD: rs80338802,
|
|
|
|
|
|
ClinVar: RCV000020096, RCV000711017, RCV001814000, RCV003473106, RCV005007872
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 10 Amish families from northern Indiana with autosomal recessive limb-girdle muscular dystrophy type 2A (LGMDR1; 253600), Richard et al. (1995) identified homozygosity for a 2306G-A transition in exon 22 of the CAPN3 gene, resulting in an arg769-to-gln (R769Q) substitution in domain IV of the protein within the third EF-hand of the helix-loop junction. The substitution occurred in a residue conserved throughout all members of the calpain family in all species. This nucleotide change was not present in patients from the 6 southern Indiana Amish LGMD families for which the chromosome 15 locus was excluded by linkage analysis, thus confirming the genetic heterogeneity of this disease in the Amish. The slowly progressive muscle weakness was usually first evident in the pelvic girdle, and then spread to the upper limbs while sparing facial muscles. Unlike the findings in Reunion Islanders, the disorder in the northern Indiana Amish appeared to be fully penetrant, and Richard et al. (1995) suggested a digenic model with a second locus to account for this inheritance pattern. </p><p>The same R769Q mutation was found by Richard et al. (1995) in affected members of a Brazilian family; the mutation was within a completely different haplotype from that observed in the Amish families. </p><p>Pratt et al. (1997) found no phenotypically normal R769Q homozygotes among 580 DNA samples from Amish individuals in a northern Indiana county. In addition, mitochondrial studies gave no evidence of a modifying mitochondrial gene. These findings argued against possible digenic inheritance postulated by Richard et al. (1995). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CAPN3, ARG572GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121434544,
|
|
|
|
|
|
gnomAD: rs121434544,
|
|
|
|
|
|
ClinVar: RCV000019180, RCV000726518, RCV001198825, RCV003323362
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In members of a family from Reunion Island who had limb-girdle muscular dystrophy type 2A (LGMDR1; 253600), Richard et al. (1995) found homozygosity for 1715G-A transition in exon 13 of the CAPN3 gene, resulting in an arg572-to-gln (R572Q) substitution inside domain III. This residue is highly conserved throughout all known calpains. The mutation, detectable by loss of a MspI restriction site, was present only in this family and in no other examined LGMD2A families or unrelated controls. It was 1 of 6 different CAPN3 mutations found in Reunion Island patients, and at least 1 more mutation was predicted from haplotype analysis. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CAPN3, ARG110TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121434545,
|
|
|
|
|
|
gnomAD: rs121434545,
|
|
|
|
|
|
ClinVar: RCV000019181, RCV001813749, RCV004998102, RCV005007873
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Brazilian family with limb-girdle muscular dystrophy type 2A (LGMDR1; 253600), Richard et al. (1995) identified a homozygous 328C-T transition in exon 2 of the CAPN3 gene, resulting in an arg110-to-ter (R110X) substitution. The parents were consanguineous. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CAPN3, SER86PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121434546,
|
|
|
|
|
|
gnomAD: rs121434546,
|
|
|
|
|
|
ClinVar: RCV000019182
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In patients with limb-girdle muscular dystrophy type 2A (LGMDR1; 253600), Richard et al. (1997) described a ser86-to-phe (S86F) mutation in the CAPN3 gene. Patients who were homozygous for this mutation had disease onset at age 6 to 7 years and presented with severe weakness in their lower limbs, leading to loss of mobility less than 8 years after onset. In contrast, their cousins who were compound heterozygotes for the S86F and P319L (114240.0005) mutations were comparatively mildly affected, with disease onset at age 15 to 17 years on average, and with loss of mobility at age 32 years for 1 of them, whereas the 2 others were still walking at ages 29 years and 28 years. All healthy heterozygotes carrying the S86F mutation had mildly elevated creatine kinase (CK) levels. This observation suggested that the mutation affects muscle cells in a somewhat dominant manner. In this kindred, 2 patients belonging to different branches of the family were diagnosed independently with polymyositis. A muscle biopsy of 1 of them showed minimal abnormalities at the limits of significance. Both patients were treated with steroids for an extended period. Eventually, family history led to a consideration of the diagnosis of muscular dystrophy. Only the identification of the pathogenic mutation allowed the definitive diagnosis of LGMD2A. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CAPN3, PRO319LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121434547,
|
|
|
|
|
|
gnomAD: rs121434547,
|
|
|
|
|
|
ClinVar: RCV000019183, RCV000417420, RCV003473107, RCV005007874
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the pro319-to-leu (P319L) mutation in the CAPN3 gene that was found in compound heterozygous state in patients with limb-girdle muscular dystrophy type 2A (LGMDR1; 253600) by Richard et al. (1997), see 114240.0004. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MYOSITIS, EOSINOPHILIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CAPN3, 2362AG-TCATCT
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1555423217, rs80338804,
|
|
|
|
|
|
gnomAD: rs80338804,
|
|
|
|
|
|
ClinVar: RCV000019184, RCV000019185, RCV000294609, RCV002490390, RCV003114199, RCV003473108
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In Guipuzcoa, a small mountainous Basque province in northern Spain, Urtasun et al. (1998) found the highest prevalence rate of limb-girdle muscular dystrophy described to that time: 69 per million. In 28 families with 38 individuals who had autosomal recessive limb-girdle muscular dystrophy type 2A (LGMDR1; 253600), mutations in the CAPN3 gene were identified. The predominant Basque mutation was a frameshift in exon 22 (2362AG-to-TCATCT). This mutation was carried by 2 different haplotypes, which were thought to have been derived from a single ancestral founder haplotype by microsatellite mutation. The common Basque frameshift mutation had previously been identified in 1 Brazilian, 1 French, and 1 American family (Richard et al., 1997). Since their data suggested a founder effect for this frameshift mutation in the Basque population, and because the families with the mutation described by Richard et al. (1997) shared the same haplotype, Urtasun et al. (1998) speculated on a Basque origin for this mutation, which could have moved to Brazil, America, and Reunion by immigration. </p><p>Krahn et al. (2006) reported 3 unrelated patients with the CAPN3 Basque mutation who were originally diagnosed with eosinophilic myositis (see 253600) based on skeletal muscle biopsy in the first decade of life. All patients presented initially with increased serum creatine kinase. Skeletal muscle biopsies showed focal inflammatory lesions with eosinophilic infiltration and necrotic muscle fibers with no evidence of parasites. Clinically, the patients had muscle weakness and difficulty walking that increased with age. Krahn et al. (2006) suggested that eosinophilic myositis may be an early and transient feature in calpainopathies, because it was not present in biopsies from older patients with typical LGMD2A. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CAPN3, 1080G-C, TRP360CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606703,
|
|
|
|
|
|
|
|
ClinVar: RCV000019186
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Kawai et al. (1998) reported on the clinical, pathologic, and genetic features of 7 patients with limb-girdle muscular dystrophy type 2A (LGMDR1; 253600) from 3 consanguineous Japanese families. The mean age of onset was 9.7 years +/- 3.1 years, and loss of ambulation occurred at 38.5 +/- 2.1 years. Muscle atrophy was predominant in the pelvic and shoulder girdles and proximal limb muscles. In 2 families, an identical 1080G-C transversion was found in the CAPN3 gene; a frameshift mutation (1796insA; 114240.0008) was found in the third family. The former mutation resulted in a trp360-to-cys (T360C) substitution in the proteolytic site of calpain-3, and the latter in a deletion of the Ca(2+)-binding domain. (In their article, Kawai et al. (1998) reported the amino acid substitution as trp360-to-cys in Figure 6 and in the text, but as trp360-to-arg in the abstract.) </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CAPN3, 1-BP INS, 1796A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80338803,
|
|
|
|
|
|
|
|
ClinVar: RCV000019187, RCV000518261, RCV001814001, RCV003473109, RCV005007875
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp insertion in the CAPN3 gene (1796insA) that was found in compound heterozygous state in patients with limb-girdle muscular dystrophy type 2A (LGMDR1; 253600) by Kawai et al. (1998), see 114240.0007. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CAPN3, 1-BP DEL, 550A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80338800,
|
|
|
|
|
|
gnomAD: rs80338800,
|
|
|
|
|
|
ClinVar: RCV000019188, RCV000078099, RCV000348995, RCV000414969, RCV000415100, RCV000415344, RCV000415373, RCV000626574, RCV000626575, RCV000626576, RCV000626577, RCV001197255, RCV001420332, RCV001849271, RCV002496413, RCV004998103
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In Croatian patients with autosomal recessive limb-girdle muscular dystrophy type 2A (LGMDR1; 253600), Canki-Klain et al. (2004) identified a 1-bp deletion (550delA) in exon 4 of the CAPN3 gene that was the most common mutation, with a prevalence of 76% of mutant CAPN3 alleles. The detection of 4 healthy 550delA heterozygous individuals yielded a frequency of 1 in 133 (0.75%) in the general Croatian population. All 4 carriers originated from an island and mountain region near the Adriatic, indicating a probable founder effect. </p><p>Fanin et al. (2005) identified the 550delA mutation in several patients with LGMD from northeastern Italy. The mutation occurred in both the homozygous state and in compound heterozygosity with another CAPN3 mutation. The 550delA mutation accounted for 9 (40%) of 23 mutant CAPN3 alleles from patients specifically from the Friuli region, and haplotype analysis indicated a founder effect. Fanin et al. (2005) concluded that LGMDR1 may be the most frequent autosomal recessive neuromuscular disorder in this region of Italy. </p><p>Todorova et al. (2007) identified mutations in the CAPN3 gene in 20 (42%) of 48 unrelated Bulgarian patients with muscular dystrophy. Forty percent of the patients were homozygous for the 500delA mutation, and 70% carried it on at least 1 allele. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CAPN3, ARG490GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121434548,
|
|
|
|
|
|
gnomAD: rs121434548,
|
|
|
|
|
|
ClinVar: RCV000019189, RCV000724646, RCV002222356, RCV002490391, RCV003473110
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In several patients with autosomal recessive limb-girdle muscular dystrophy type 2A (LGMDR1; 253600) from 3 unrelated families in northeastern Italy, Fanin et al. (2005) identified a homozygous arg490-to-gln (R490Q) mutation in the CAPN3 gene. Another patient was compound heterozygous for the R490Q mutation and 550delA (114240.0009). The R490Q mutation accounted for 6 (46%) of 13 mutant CAPN3 alleles from patients specifically from the Venezia district, and haplotype analysis indicated a founder effect. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL DOMINANT 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CAPN3, 21-BP DEL, NT643
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs863224965,
|
|
|
|
|
|
|
|
ClinVar: RCV000201156, RCV000379696, RCV000681607, RCV004998418
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 36 patients from 10 families of northern European descent with autosomal dominant limb-girdle muscular dystrophy type 1I (LGMDD4; 618129), Vissing et al. (2016) identified a heterozygous in-frame 21-bp deletion (c.643_663del21, NM_000070) in the CAPN3 gene. The variant is present at an allele frequency of 0.006% among individuals of European descent in the ExAC database. Haplotype analysis of 4 families indicated a founder effect. Analysis of several patients' muscle tissue showed normal mRNA levels and no evidence of nonsense-mediated mRNA decay, but significantly decreased CAPN3 protein levels, at less than 15% of control values. Vissing et al. (2016) postulated that the in-frame nature of the mutation may have led to expression of a mutated protein that could have a dominant-negative effect. </p><p>In 3 unrelated patients of northern European descent with LGMDD4, Martinez-Thompson et al. (2018) identified the same heterozygous 21-bp deletion in the CAPN3 gene that had been reported by Vissing et al. (2016). The deletion resulted in the deletion of residues Ser215_Gly221 in the first structural domain. The mutations were found by next-generation, whole-exome, or Sanger sequencing; all were confirmed by Sanger sequencing. Each proband had a family history of the disorder, although not all affected family members were available for genetic testing. Functional studies of the variant were not performed, but Western blot analysis of patient tissues showed greatly decreased amounts of the CAPN3 protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Blazquez, L., Azpitarte, M., Saenz, A., Goicoechea, M., Otaegui, D., Ferrer, X., Illa, I., Gutierrez-Rivas, E., Vilchez, J. J., Lopez de Munain, A.
|
|
<strong>Characterization of novel CAPN3 isoforms in white blood cells: an alternative approach for limb-girdle muscular dystrophy 2A diagnosis.</strong>
|
|
Neurogenetics 9: 173-182, 2008.
|
|
|
|
|
|
[PubMed: 18563459]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10048-008-0129-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Canki-Klain, N., Milic, A., Kovac, B., Trlaja, A., Grgicevic, D., Zurak, N., Fardeau, M., Leturcq, F., Kaplan, J.-C., Urtizberea, J. A., Politano, L., Piluso, G., Feingold, J.
|
|
<strong>Prevalence of the 550delA mutation in calpainopathy (LGMD 2A) in Croatia.</strong>
|
|
Am. J. Med. Genet. 125A: 152-156, 2004. Note: Erratum: Am. J. Med. Genet. 130A: 218 only, 2004.
|
|
|
|
|
|
[PubMed: 14981715]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.20408]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Duno, M., Sveen, M.-L., Schwartz, M., Vissing, J.
|
|
<strong>cDNA analyses of CAPN3 enhances mutation detection and reveals a low prevalence of LGMD2A patients in Denmark.</strong>
|
|
Europ. J. Hum. Genet. 16: 935-940, 2008.
|
|
|
|
|
|
[PubMed: 18337726]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ejhg.2008.47]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fanin, M., Nascimbeni, A. C., Angelini, C.
|
|
<strong>Screening of calpain-3 autolytic activity in LGMD muscle: a functional map of CAPN3 gene mutations.</strong>
|
|
J. Med. Genet. 44: 38-43, 2007.
|
|
|
|
|
|
[PubMed: 16971480]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2006.044859]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fanin, M., Nascimbeni, A. C., Fulizio, L., Angelini, C.
|
|
<strong>The frequency of limb girdle muscular dystrophy 2A in northeastern Italy.</strong>
|
|
Neuromusc. Disord. 15: 218-224, 2005.
|
|
|
|
|
|
[PubMed: 15725583]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.nmd.2004.11.003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Huang, Y., de Morree, A., van Remoortere, A., Bushby, K., Frants, R. R., Dunnen, J. T., van der Maarel, S.
|
|
<strong>Calpain 3 is a modulator of the dysferlin protein complex in skeletal muscle.</strong>
|
|
Hum. Molec. Genet. 17: 1855-1866, 2008.
|
|
|
|
|
|
[PubMed: 18334579]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddn081]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Huebsch, K. A., Kudryashova, E., Wooley, C. M., Sher, R. B., Seburn, K. L., Spencer, M. J., Cox, G. A.
|
|
<strong>Mdm muscular dystrophy: interactions with calpain 3 and a novel functional role for titin's N2A domain.</strong>
|
|
Hum. Molec. Genet. 14: 2801-2811, 2005.
|
|
|
|
|
|
[PubMed: 16115818]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi313]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kawai, H., Akaike, M., Kunishige, M., Inui, T., Adachi, K., Kimura, C., Kawajiri, M., Nishida, Y., Endo, I., Kashiwagi, S., Nishino, H., Fujiwara, T., Okuno, S., Roudaut, C., Richard, I., Beckmann, J. S., Miyoshi, K., Matsumoto, T.
|
|
<strong>Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families.</strong>
|
|
Muscle Nerve 21: 1493-1501, 1998.
|
|
|
|
|
|
[PubMed: 9771675]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1097-4598(199811)21:11<1493::aid-mus19>3.0.co;2-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Krahn, M., Lopez de Munain, A., Streichenberger, N., Bernard, R., Pecheux, C., Testard, H., Pena-Segura, J. L., Yoldi, E., Cabello, A., Romero, N. B., Poza, J. J., Bouillot-Eimer, S., Ferrer, X., Goicoechea, M., Garcia-Bragado, F., Leturcq, F., Urtizberea, J. A., Levy, N.
|
|
<strong>CAPN3 mutations in patients with idiopathic eosinophilic myositis.</strong>
|
|
Ann. Neurol. 59: 905-911, 2006.
|
|
|
|
|
|
[PubMed: 16607617]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.20833]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kramerova, I., Kudryashova, E., Tidball, J. G., Spencer, M. J.
|
|
<strong>Null mutation of calpain 3 (p94) in mice causes abnormal sarcomere formation in vivo and in vitro.</strong>
|
|
Hum. Molec. Genet. 13: 1373-1388, 2004.
|
|
|
|
|
|
[PubMed: 15138196]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddh153]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kramerova, I., Kudryashova, E., Venkatraman, G., Spencer, M. J.
|
|
<strong>Calpain 3 participates in sarcomere remodeling by acting upstream of the ubiquitin-proteasome pathway.</strong>
|
|
Hum. Molec. Genet. 14: 2125-2134, 2005. Note: Erratum: Hum. Molec. Genet. 16: 1006 only, 2007.
|
|
|
|
|
|
[PubMed: 15961411]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi217]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kramerova, I., Kudryashova, E., Wu, B., Germain, S., Vandenborne, K., Romain, N., Haller, R. G., Verity, M. A., Spencer, M. J.
|
|
<strong>Mitochondrial abnormalities, energy deficit and oxidative stress are features of calpain 3 deficiency in skeletal muscle.</strong>
|
|
Hum. Molec. Genet. 18: 3194-3205, 2009.
|
|
|
|
|
|
[PubMed: 19483197]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp257]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Martinez-Thompson, J. M., Niu, Z., Tracy, J. A., Moore, S. A., Swenson, A., Wieben, E. D., Milone, M.
|
|
<strong>Autosomal dominant calpainopathy due to heterozygous CAPN3 c.643_663del21.</strong>
|
|
Muscle Nerve. 57: 679-683, 2018.
|
|
|
|
|
|
[PubMed: 28881388]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/mus.25970]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ohno, S., Minoshima, S., Kudoh, J., Fukuyama, R., Ohmi-Imajoh, S., Suzuki, K., Shimizu, Y., Shimizu, N.
|
|
<strong>Four genes for the calpain family locate on four distinct human chromosomes.</strong>
|
|
Cytogenet. Cell Genet. 53: 225-229, 1990.
|
|
|
|
|
|
[PubMed: 2209092]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000132937]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ono, Y., Shimada, H., Sorimachi, H., Richard, I., Saido, T. C., Beckmann, J. S., Ishiura, S., Suzuki, K.
|
|
<strong>Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A.</strong>
|
|
J. Biol. Chem. 273: 17073-17078, 1998.
|
|
|
|
|
|
[PubMed: 9642272]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.273.27.17073]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Piluso, G., Politano, L., Aurino, S., Fanin, M., Ricci, E., Ventriglia, V. M., Belsito, A., Totaro, A., Saccone, V., Topaloglu, H., Nascimbeni, A. C., Fulizio, L., Broccolini, A., Canki-Klain, N., Comi, L. I., Nigro, G., Angelini, C., Nigro, V.
|
|
<strong>Extensive scanning of the calpain-3 gene broadens the spectrum of LGMD2A phenotypes.</strong>
|
|
J. Med. Genet. 42: 686-693, 2005.
|
|
|
|
|
|
[PubMed: 16141003]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2004.028738]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pratt, V. M., Jackson, C. E., Wallace, D. C., Gurley, D. S., Feit, A., Feldman, G. L.
|
|
<strong>DNA studies of limb-girdle muscular dystrophy type 2A in the Amish exclude a modifying mitochondrial gene and show no evidence for a modifying nuclear gene. (Letter)</strong>
|
|
Am. J. Hum. Genet. 61: 231-233, 1997.
|
|
|
|
|
|
[PubMed: 9246005]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0002-9297(07)64296-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Richard, I., Beckmann, J. S.
|
|
<strong>Molecular cloning of mouse Canp3, the gene associated with limb-girdle muscular dystrophy 2A in human.</strong>
|
|
Mammalian Genome 7: 377-379, 1996.
|
|
|
|
|
|
[PubMed: 8661728]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s003359900108]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Richard, I., Brenguier, L., Dincer, P., Roudaut, C., Bady, B., Burgunder, J.-M., Chemaly, R., Garcia, C. A., Halaby, G., Jackson, C. E., Kurnit, D. M., Lefranc, G., Legum, C., Loiselet, J., Merlini, L., Nivelon-Chevallier, A., Ollagnon-Roman, E., Restagno, G., Topaloglu, H., Beckmann, J. S.
|
|
<strong>Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins.</strong>
|
|
Am. J. Hum. Genet. 60: 1128-1138, 1997.
|
|
|
|
|
|
[PubMed: 9150160]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Richard, I., Broux, O., Allamand, V., Fougerousse, F., Chiannilkulchai, N., Bourg, N., Brenguier, L., Devaud, C., Pasturaud, P., Roudaut, C., Hillaire, D., Passos-Bueno, M.-R., Zatz, M., Tischfield, J. A., Fardeau, M., Jackson, C. E., Cohen, D., Beckmann, J. S.
|
|
<strong>Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.</strong>
|
|
Cell 81: 27-40, 1995.
|
|
|
|
|
|
[PubMed: 7720071]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(95)90368-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sarparanta, J., Blandin, G., Charton, K., Vihola, A., Marchand, S., Milic, A., Hackman, P., Ehler, E., Richard, I., Udd, B.
|
|
<strong>Interactions with M-band titin and calpain 3 link myospryn (CMYA5) to tibial and limb-girdle muscular dystrophies.</strong>
|
|
J. Biol. Chem. 285: 30304-30315, 2010.
|
|
|
|
|
|
[PubMed: 20634290]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M110.108720]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sorimachi, H., Imajoh-Ohmi, S., Emori, Y., Kawasaki, H., Ohno, S., Minami, Y., Suzuki, K.
|
|
<strong>Molecular cloning of a novel mammalian calcium-dependent protease distinct from both m- and mu-types: specific expression of the mRNA in skeletal muscle.</strong>
|
|
J. Biol. Chem. 264: 20106-20111, 1989.
|
|
|
|
|
|
[PubMed: 2555341]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tagawa, K., Taya, C., Hayashi, Y., Nakagawa, M., Ono, Y., Fukuda, R., Karasuyama, H., Toyama-Sorimachi, N., Katsui, Y., Hata, S., Ishiura, S., Nonaka, I., Seyama, Y., Arahata, K., Yonekawa, H., Sorimachi, H., Suzuki, K.
|
|
<strong>Myopathy phenotype of transgenic mice expressing active site-mutated inactive p94 skeletal muscle-specific calpain, the gene product responsible for limb girdle muscular dystrophy type 2A.</strong>
|
|
Hum. Molec. Genet. 9: 1393-1402, 2000.
|
|
|
|
|
|
[PubMed: 10814721]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/9.9.1393]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Todorova, A., Georgieva, B., Tournev, I., Todorov, T., Bogdanova, N., Mitev, V., Mueller, C. R., Kremensky, I., Horst, J.
|
|
<strong>A large deletion and novel point mutations in the calpain 3 gene (CAPN3) in Bulgarian LGMD2A patients.</strong>
|
|
Neurogenetics 8: 225-229, 2007.
|
|
|
|
|
|
[PubMed: 17318636]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10048-007-0083-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Urtasun, M., Saenz, A., Roudaut, C., Poza, J. J., Urtizberea, J. A., Cobo, A. M., Richard, I., Garcia Bragado, F., Leturcq, F., Kaplan, J. C., Marti Masso, J. F., Beckmann, J. S., Lopez de Munain, A.
|
|
<strong>Limb-girdle muscular dystrophy in Guipuzcoa (Basque Country, Spain).</strong>
|
|
Brain 121: 1735-1747, 1998.
|
|
|
|
|
|
[PubMed: 9762961]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/121.9.1735]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vissing, J., Barresi, R., Witting, N., Van Ghelue, M., Gammelgaard, L., Bindoff, L. A., Straub, V., Lochmuller, H., Hudson, J., Wahl, C. M., Arnardottir, S., Dahlbom, K., Jonsrud, C., Duno, M.
|
|
<strong>A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy.</strong>
|
|
Brain 139: 2154-2163, 2016.
|
|
|
|
|
|
[PubMed: 27259757]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/aww133]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zatz, M., Starling, A.
|
|
<strong>Calpains and disease.</strong>
|
|
New Eng. J. Med. 352: 2413-2423, 2005.
|
|
|
|
|
|
[PubMed: 15944426]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMra043361]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 09/20/2018<br>Patricia A. Hartz - updated : 2/14/2012<br>George E. Tiller - updated : 7/7/2010<br>Cassandra L. Kniffin - updated : 12/8/2009<br>George E. Tiller - updated : 11/19/2008<br>Cassandra L. Kniffin - reorganized : 11/12/2008<br>Cassandra L. Kniffin - updated : 11/3/2008<br>Cassandra L. Kniffin - updated : 8/19/2008<br>Cassandra L. Kniffin - updated : 9/21/2007<br>Cassandra L. Kniffin - updated : 9/10/2007<br>Cassandra L. Kniffin - updated : 8/21/2007<br>Victor A. McKusick - updated : 2/21/2007<br>George E. Tiller - updated : 9/11/2006<br>Victor A. McKusick - updated : 12/20/2005<br>Victor A. McKusick - updated : 6/24/2005<br>Cassandra L. Kniffin - updated : 4/12/2005<br>George E. Tiller - updated : 8/8/2000<br>Victor A. McKusick - updated : 1/7/2000<br>Victor A. McKusick - updated : 1/5/2000<br>Victor A. McKusick - updated : 8/20/1997<br>Victor A. McKusick - updated : 6/16/1997
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 6/5/1989
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 09/27/2018<br>carol : 09/26/2018<br>carol : 09/25/2018<br>ckniffin : 09/20/2018<br>carol : 08/05/2016<br>carol : 05/21/2015<br>mcolton : 5/19/2015<br>carol : 11/11/2013<br>mgross : 2/17/2012<br>terry : 2/14/2012<br>carol : 7/29/2010<br>wwang : 7/19/2010<br>terry : 7/7/2010<br>wwang : 2/23/2010<br>ckniffin : 2/19/2010<br>wwang : 1/4/2010<br>ckniffin : 12/8/2009<br>wwang : 5/7/2009<br>wwang : 11/19/2008<br>carol : 11/12/2008<br>ckniffin : 11/3/2008<br>wwang : 8/28/2008<br>ckniffin : 8/19/2008<br>wwang : 9/27/2007<br>ckniffin : 9/21/2007<br>wwang : 9/13/2007<br>ckniffin : 9/10/2007<br>wwang : 9/5/2007<br>ckniffin : 8/21/2007<br>alopez : 2/23/2007<br>terry : 2/21/2007<br>alopez : 9/11/2006<br>wwang : 12/28/2005<br>terry : 12/20/2005<br>alopez : 6/27/2005<br>terry : 6/24/2005<br>tkritzer : 4/14/2005<br>ckniffin : 4/12/2005<br>carol : 10/20/2003<br>carol : 10/17/2003<br>alopez : 8/8/2000<br>psherman : 4/10/2000<br>carol : 1/28/2000<br>carol : 1/28/2000<br>alopez : 1/14/2000<br>terry : 1/7/2000<br>carol : 1/5/2000<br>terry : 1/5/2000<br>carol : 4/21/1999<br>mgross : 4/8/1999<br>alopez : 9/16/1998<br>terry : 9/14/1998<br>carol : 8/18/1998<br>carol : 8/18/1998<br>terry : 6/26/1998<br>terry : 8/25/1997<br>terry : 8/20/1997<br>terry : 6/23/1997<br>terry : 6/16/1997<br>jamie : 1/15/1997<br>terry : 1/8/1997<br>mark : 6/14/1996<br>terry : 6/14/1996<br>terry : 6/11/1996<br>mark : 11/17/1995<br>terry : 6/3/1995<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>carol : 12/19/1989<br>ddp : 10/26/1989
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div id="mimFooter">
|
|
|
|
|
|
<div class="container ">
|
|
<div class="row">
|
|
<br />
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="hidden-print mim-footer">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="visible-print-block mim-footer" style="position: relative;">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
<br />
|
|
Printed: March 5, 2025
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
|
|
<div class="modal-dialog" role="document">
|
|
<div class="modal-content">
|
|
<div class="modal-header">
|
|
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">×</span></button>
|
|
<h4 class="modal-title" id="mimDonationPopupModalTitle">
|
|
OMIM Donation:
|
|
</h4>
|
|
</div>
|
|
<div class="modal-body">
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Dear OMIM User,
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
To ensure long-term funding for the OMIM project, we have diversified
|
|
our revenue stream. We are determined to keep this website freely
|
|
accessible. Unfortunately, it is not free to produce. Expert curators
|
|
review the literature and organize it to facilitate your work. Over 90%
|
|
of the OMIM's operating expenses go to salary support for MD and PhD
|
|
science writers and biocurators. Please join your colleagues by making a
|
|
donation now and again in the future. Donations are an important
|
|
component of our efforts to ensure long-term funding to provide you the
|
|
information that you need at your fingertips.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Thank you in advance for your generous support, <br />
|
|
Ada Hamosh, MD, MPH <br />
|
|
Scientific Director, OMIM <br />
|
|
</p>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div class="modal-footer">
|
|
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
</body>
|
|
|
|
</html>
|
|
|
|
|