10736 lines
1.1 MiB
10736 lines
1.1 MiB
|
|
|
|
|
|
|
|
|
|
<!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
|
|
|
|
- *180901 - RYANODINE RECEPTOR 1; RYR1
|
|
|
|
|
|
- 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=180901"><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">*180901</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="#geneFunction">Gene Function</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="#biochemicalFeatures">Biochemical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</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="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#populationGenetics">Population 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/180901">Table View</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#seeAlso"><strong>See Also</strong></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=ENSG00000196218;t=ENST00000359596" 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=6261" 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=180901" 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=ENSG00000196218;t=ENST00000359596" 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_000540,NM_001042723,XM_006723317,XM_006723319,XM_011527205,XM_047439202" 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_000540" 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=180901" 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=01618&isoform_id=01618_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/RYR1" 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/337722,553643,579583,944949,1216475,3328201,3845349,7656700,8167726,18181960,18181962,62088430,108935904,113204615,113204617,119577199,119577200,119577201,119577202,194375708,365768447,365768791,444737843,578834742,578834746,768010467,2217322381,2462566812,2462566814,2462566816,2462566818" 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/P21817" 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=6261" 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=ENSG00000196218;t=ENST00000359596" 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=RYR1" 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=RYR1" 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+6261" 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/RYR1" 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:6261" 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/6261" 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=chr19&hgg_gene=ENST00000359596.8&hgg_start=38433691&hgg_end=38587564&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:10483" 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:10483" 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/ryr1" 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=180901[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=180901[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/RYR1/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/ENSG00000196218" 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=RYR1" 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=RYR1" 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=RYR1" 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/RYR1" 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=RYR1&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/PA34896" 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:10483" 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/FBgn0011286.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:99659" 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/RYR1#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:99659" 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/6261/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/OMIA000621/" 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=6261" 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="https://wormbase.org/db/gene/gene?name=WBGene00006801;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-020108-2" 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:180901" 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:6261" 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=RYR1&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> 764957003<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> G71.29<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>
|
|
180901
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
RYANODINE RECEPTOR 1; RYR1
|
|
|
|
</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">
|
|
RYANODINE RECEPTOR, SKELETAL MUSCLE; RYDR<br />
|
|
SKELETAL MUSCLE RYANODINE RECEPTOR; SKRR<br />
|
|
SARCOPLASMIC RETICULUM CALCIUM RELEASE CHANNEL
|
|
</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=RYR1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">RYR1</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/19/649?start=-3&limit=10&highlight=649">19q13.2</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr19:38433691-38587564&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'})">19:38,433,691-38,587,564</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=145600,117000,255320,619542" 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="4">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/19/649?start=-3&limit=10&highlight=649">
|
|
19q13.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
{Malignant hyperthermia susceptibility 1}
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/145600"> 145600 </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">
|
|
Congenital myopathy 1A, autosomal dominant, with susceptibility to malignant hyperthermia
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/117000"> 117000 </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">
|
|
Congenital myopathy 1B, autosomal recessive
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/255320"> 255320 </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>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
King-Denborough syndrome
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/619542"> 619542 </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>
|
|
|
|
|
|
|
|
|
|
</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/180901" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/180901" 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 RYR1 gene encodes the skeletal muscle ryanodine receptor, which serves as a calcium release channel of the sarcoplasmic reticulum as well as a bridging structure connecting the sarcoplasmic reticulum and transverse tubule (<a href="#48" class="mim-tip-reference" title="MacLennan, D. H., Zorzato, F., Fujii, J., Otsu, K., Phillips, M., Lai, F. A., Meissner, G., Green, N. M., Willard, H. F., Britt, B. A., Worton, R. G., Korneluk, R. G. <strong>Cloning and localization of the human calcium release channel (ryanodine receptor) gene to the proximal long arm (cen-q13.2) of human chromosome 19. (Abstract)</strong> Am. J. Hum. Genet. 45 (suppl.): A205 only, 1989."None>MacLennan et al., 1989</a>).</p><p>See also RYR2 (<a href="/entry/180902">180902</a>) and RYR3 (<a href="/entry/180903">180903</a>), which encode the cardiac and brain ryanodine receptors, respectively.</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="#48" class="mim-tip-reference" title="MacLennan, D. H., Zorzato, F., Fujii, J., Otsu, K., Phillips, M., Lai, F. A., Meissner, G., Green, N. M., Willard, H. F., Britt, B. A., Worton, R. G., Korneluk, R. G. <strong>Cloning and localization of the human calcium release channel (ryanodine receptor) gene to the proximal long arm (cen-q13.2) of human chromosome 19. (Abstract)</strong> Am. J. Hum. Genet. 45 (suppl.): A205 only, 1989."None>MacLennan et al. (1989)</a> and <a href="#94" class="mim-tip-reference" title="Zorzato, F., Fujii, J., Otsu, K., Phillips, M., Green, N. M., Lai, F. A., Meissner, G., MacLennan, D. H. <strong>Molecular cloning of cDNA encoding human and rabbit forms of the Ca(2+) release channel (ryanodine receptor) of skeletal muscle sarcoplasmic reticulum.</strong> J. Biol. Chem. 265: 2244-2256, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2298749/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2298749</a>]" pmid="2298749">Zorzato et al. (1990)</a> cloned cDNAs encoding the rabbit and human ryanodine receptors. The human cDNA encodes a 5,032-amino acid protein with a molecular mass of 563.5 kD, which is made without an N-terminal sequence. Sequence analysis predicts 10 potential transmembrane sequences in the C-terminal region and 2 additional potential transmembrane sequences closer to the center of the molecule, which could form the calcium-conducting pore. The remainder of the protein is hydrophilic and presumably constitutes the cytoplasmic domain. Several potential calmodulin (see <a href="/entry/114180">114180</a>)-binding sites were observed between residues 2800 and 3050. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2298749" 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><a href="#21" class="mim-tip-reference" title="Eu, J. P., Sun, J., Xu, L., Stamler, J. S., Meissner, G. <strong>The skeletal muscle calcium release channel: coupled O2 sensor and NO signaling functions.</strong> Cell 102: 499-509, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10966111/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10966111</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)00054-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10966111">Eu et al. (2000)</a> reported that ambient oxygen tension (pO2) dynamically controls the redox state of 6 to 8 out of 50 thiols in each RYR1 subunit and thereby tunes the response to NO. At physiologic pO2, nanomolar NO activates the channel by S-nitrosylating a single cysteine residue. Among sarcoplasmic reticulum proteins, S-nitrosylation is specific to RYR1, and its effect on the channel is calmodulin (see <a href="/entry/114180">114180</a>) dependent. Neither activation nor S-nitrosylation of the channel occurs at ambient pO2. The demonstration that channel cysteine residues subserve coupled O2 sensor and NO regulatory functions, and that these operate through the prototypic allosteric effector calmodulin, may have general implications for the regulation of redox-related systems. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10966111" 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>Calcium-induced calcium release is a general mechanism that most cells use to amplify calcium signals. In heart cells, this mechanism is operated between voltage-gated L-type calcium channels (LCCs; see <a href="/entry/114205">114205</a>) in the plasma membrane and calcium release channels, commonly known as ryanodine receptors, in the sarcoplasmic reticulum. The calcium influx through LCCs traverses a cleft of roughly 12 nm formed by the cell surface and the sarcoplasmic reticulum membrane, and activates adjacent ryanodine receptors to release calcium in the form of calcium sparks (<a href="#12" class="mim-tip-reference" title="Cheng, H., Lederer, W. J., Cannell, M. B. <strong>Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle.</strong> Science 262: 740-744, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8235594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8235594</a>] [<a href="https://doi.org/10.1126/science.8235594" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8235594">Cheng et al., 1993</a>). <a href="#86" class="mim-tip-reference" title="Wang, S.-Q., Song, L.-S., Lakatta, E. G., Cheng, H. <strong>Ca(2+) signalling between single L-type Ca(2+) channels and ryanodine receptors in heart cells.</strong> Nature 410: 592-596, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11279498/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11279498</a>] [<a href="https://doi.org/10.1038/35069083" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11279498">Wang et al. (2001)</a> determined the kinetics, fidelity, and stoichiometry of coupling between LCCs and ryanodine receptors. They showed that the local calcium signal produced by a single opening of an LCC, named a 'calcium sparklet,' can trigger about 4 to 6 ryanodine receptors to generate a calcium spark. The coupling between LCCs and ryanodine receptors is stochastic, as judged by the exponential distribution of the coupling latency. The fraction of sparklets that successfully triggers a spark is less than unity and declines in a use-dependent manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8235594+11279498" 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="#16" class="mim-tip-reference" title="Ducreux, S., Zorzato, F., Muller, C., Sewry, C., Muntoni, F., Quinlivan, R., Restagno, G., Girard, T., Treves, S. <strong>Effect of ryanodine receptor mutations on interleukin-6 release and intracellular calcium homeostasis in human myotubes from malignant hyperthermia-susceptible individuals and patients affected by central core disease.</strong> J. Biol. Chem. 279: 43838-43846, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15299003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15299003</a>] [<a href="https://doi.org/10.1074/jbc.M403612200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15299003">Ducreux et al. (2004)</a> found that activation of RYR1 caused release of interleukin-6 (IL6; <a href="/entry/147620">147620</a>) from cultured human myotubes. Maximal release was obtained 4 to 6 hours later, suggesting that IL6 was newly transcribed and synthesized. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15299003" 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>Epigenetic regulation of gene expression is a source of genetic variation, which can mimic recessive mutations by creating transcriptional haploinsufficiency. Germline epimutations and genomic imprinting are typical examples. Genomic imprinting can be tissue-specific, with biallelic expression in some tissues and monoallelic expression in others or with polymorphic expression in the general population. During the RYR1 mutation analysis of a cohort of patients with recessive core myopathies, <a href="#93" class="mim-tip-reference" title="Zhou, H., Brockington, M., Jungbluth, H., Monk, D., Stanier, P., Sewry, C. A., Moore, G. E., Muntoni, F. <strong>Epigenetic allele silencing unveils recessive RYR1 mutations in core myopathies.</strong> Am. J. Hum. Genet. 79: 859-868, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033962</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033962[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/10.1086/508500" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033962">Zhou et al. (2006)</a> discovered that 6 (55%) of 11 patients had monoallelic RYR1 transcription in skeletal muscle, despite being heterozygous at the genomic level. In families for which parental DNA was available, segregation studies showed that the nonexpressed allele was maternally inherited. Transcription analysis in patients' fibroblasts and lymphoblastoid cell lines indicated biallelic expression, which suggested tissue-specific silencing. Transcription analysis of normal human fetal tissues showed that RYR1 is monoallelically expressed in skeletal and smooth muscle, brain, and eye in 10% of cases. In contrast, 25 normal adult human skeletal muscle samples displayed only biallelic expression. Finally, the administration of the DNA methyltransferase inhibitor 5-aza-deoxycytidine to cultured patient skeletal muscle myoblasts reactivated the transcription of the silenced allele, which suggested hypermethylation as a mechanism for RYR1 silencing. The data indicated that RYR1 undergoes polymorphic, tissue-specific, and developmentally regulated allele silencing and that this unveils recessive mutations in patients with core myopathies. The data also suggested that imprinting is a likely mechanism for this phenomenon and that similar mechanisms could play a role in human phenotypic heterogeneity. <a href="#42" class="mim-tip-reference" title="Klein, A., Lillis, S., Munteanu, I., Scoto, M., Zhou, H., Quinlivan, R., Straub, V., Manzur, A. Y., Roper, H., Jeannet, P-Y., Rakowicz, W., Jones, D. H., and 20 others. <strong>Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.</strong> Hum. Mutat. 33: 981-988, 2012. Note: Erratum: Hum. Mutat. 33: 1310, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22473935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22473935</a>] [<a href="https://doi.org/10.1002/humu.22056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22473935">Klein et al. (2012)</a> found that some of the patients reported by <a href="#93" class="mim-tip-reference" title="Zhou, H., Brockington, M., Jungbluth, H., Monk, D., Stanier, P., Sewry, C. A., Moore, G. E., Muntoni, F. <strong>Epigenetic allele silencing unveils recessive RYR1 mutations in core myopathies.</strong> Am. J. Hum. Genet. 79: 859-868, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033962</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033962[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/10.1086/508500" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033962">Zhou et al. (2006)</a> with apparent mutations expressed monoallelically in the skeletal muscle were found to have another stop RYR1 mutation, resulting in nonsense-mediated mRNA decay and lack of expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17033962+22473935" 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="#64" class="mim-tip-reference" title="Phillips, M. S., Fujii, J., Khanna, V. K., DeLeon, S., Yokobata, K., De Jong, P. J., MacLennan, D. H. <strong>The structural organization of the human skeletal muscle ryanodine receptor (RYR1) gene.</strong> Genomics 34: 24-41, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8661021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8661021</a>] [<a href="https://doi.org/10.1006/geno.1996.0238" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8661021">Phillips et al. (1996)</a> reported that the RYR1 gene contains 106 exons, of which 2 are alternatively spliced. The length of the gene was estimated to be approximately 160 kb. The numbering of the nucleotides comprising the RYR1 cDNA and the numbering of amino acids encoded by them were corrected to account for earlier errors and omissions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8661021" 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="biochemicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimBiochemicalFeaturesFold" id="mimBiochemicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimBiochemicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimBiochemicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
<a href="#85" class="mim-tip-reference" title="Tung, C.-C., Lobo, P. A., Kimlicka, L., Van Petegem, F. <strong>The amino-terminal disease hotspot of ryanodine receptors forms a cytoplasmic vestibule.</strong> Nature 468: 585-588, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21048710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21048710</a>] [<a href="https://doi.org/10.1038/nature09471" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21048710">Tung et al. (2010)</a> showed the 2.5-angstrom resolution crystal structure of a region spanning 3 domains of RyR1, encompassing amino acid residues 1-559. The domains interact with each other through a predominantly hydrophilic interface. Docking in RyR1 electron microscopy maps unambiguously places the domains in the cytoplasmic portion of the channel, forming a 240-kD cytoplasmic vestibule around the 4-fold symmetry axis. <a href="#85" class="mim-tip-reference" title="Tung, C.-C., Lobo, P. A., Kimlicka, L., Van Petegem, F. <strong>The amino-terminal disease hotspot of ryanodine receptors forms a cytoplasmic vestibule.</strong> Nature 468: 585-588, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21048710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21048710</a>] [<a href="https://doi.org/10.1038/nature09471" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21048710">Tung et al. (2010)</a> pinpointed the exact locations of more than 50 disease-associated mutations in full-length RyR1 and RyR2 (<a href="/entry/180902">180902</a>). The mutations can be classified into 3 groups: those that destabilize the interfaces between the 3 amino-terminal domains, disturb the folding of individual domains, or affect 1 of the 6 interfaces with other parts of the receptor. <a href="#85" class="mim-tip-reference" title="Tung, C.-C., Lobo, P. A., Kimlicka, L., Van Petegem, F. <strong>The amino-terminal disease hotspot of ryanodine receptors forms a cytoplasmic vestibule.</strong> Nature 468: 585-588, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21048710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21048710</a>] [<a href="https://doi.org/10.1038/nature09471" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21048710">Tung et al. (2010)</a> proposed a model whereby the opening of RyR coincides with allosterically couples motions within the N-terminal domains. This process can be affected by mutations that target various interfaces within and across subunits. <a href="#85" class="mim-tip-reference" title="Tung, C.-C., Lobo, P. A., Kimlicka, L., Van Petegem, F. <strong>The amino-terminal disease hotspot of ryanodine receptors forms a cytoplasmic vestibule.</strong> Nature 468: 585-588, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21048710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21048710</a>] [<a href="https://doi.org/10.1038/nature09471" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21048710">Tung et al. (2010)</a> suggested that the crystal structure provides a framework to understand the many disease-associated mutations in RyRs that have been studied using functional methods, and would be useful for developing new strategies to modulate RyR function in disease states. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21048710" 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>Using electron cryomicroscopy, <a href="#18" class="mim-tip-reference" title="Efremov, R. G., Leitner, A., Aebersold, R., Raunser, S. <strong>Architecture and conformational switch mechanism of the ryanodine receptor.</strong> Nature 517: 39-43, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25470059/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25470059</a>] [<a href="https://doi.org/10.1038/nature13916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25470059">Efremov et al. (2015)</a> determined the architecture of rabbit Ryr1 at a resolution of 6.1 angstroms and showed that the cytoplasmic moiety of Ryr1 contains 2 large alpha-solenoid domains and several smaller domains, with folds suggestive of participation in protein-protein interactions. The transmembrane domain represents a chimera of voltage-gated sodium and pH-activated ion channels. <a href="#18" class="mim-tip-reference" title="Efremov, R. G., Leitner, A., Aebersold, R., Raunser, S. <strong>Architecture and conformational switch mechanism of the ryanodine receptor.</strong> Nature 517: 39-43, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25470059/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25470059</a>] [<a href="https://doi.org/10.1038/nature13916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25470059">Efremov et al. (2015)</a> identified the calcium-binding EF-hand domain and showed that it functions as a conformational switch allosterically gating the channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25470059" 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="#91" class="mim-tip-reference" title="Zalk, R., Clarke, O. B., des Georges, A., Grassucci, R. A., Reiken, S., Mancia, F., Hendrickson, W. A., Frank, J., Marks, A. R. <strong>Structure of a mammalian ryanodine receptor.</strong> Nature 517: 44-49, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25470061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25470061</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25470061[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/10.1038/nature13950" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25470061">Zalk et al. (2015)</a> reported the closed-state structure of the 2.3-megadalton complex of rabbit Ryr1, solved by single-particle electron cryomicroscopy at an overall resolution of 4.8 angstroms. They fitted a polyalanine-level model to all 3,757 ordered residues in each protomer, defining the transmembrane pore in great detail and placing all cytosolic domains as tertiary folds. The cytosolic assembly is built on an extended alpha-solenoid scaffold connecting key regulatory domains to the pore. The Ryr1 pore architecture places it in the 6-transmembrane ion channel superfamily. A unique domain inserted between the second and third transmembrane helices interacts intimately with paired EF hands originating from the alpha-solenoid scaffold, suggesting a mechanism for channel gating by calcium. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25470061" 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="#90" class="mim-tip-reference" title="Yan, Z., Bai, X., Yan, C., Wu, J., Li, Z., Xie, T., Peng, W., Yin, C., Li, X., Scheres, S. H. W., Shi, Y., Yan, N. <strong>Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution.</strong> Nature 517: 50-55, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25517095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25517095</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25517095[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/10.1038/nature14063" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25517095">Yan et al. (2015)</a> reported the structure of rabbit Ryr1 in complex with its modulator FKBP12 (<a href="/entry/186945">186945</a>) at an overall resolution of 3.8 angstroms, determined by single-particle electron cryomicroscopy. Three domains, named central, handle, and helical domains, display the armadillo repeat fold. These domains, together with the amino-terminal domain, constitute a network of superhelical scaffold for binding and propagation of conformational changes. The channel domain exhibits the voltage-gated ion channel superfamily fold with distinct features. A negative charge-enriched hairpin loop connecting S5 and the pore helix is positioned above the entrance to the selectivity-filter vestibule. The 4 elongated S6 segments form a right-handed helical bundle that closes the pore at the cytoplasmic border of the membrane. Allosteric regulation of the pore by the cytoplasmic domains is mediated through extensive interactions between the central domains and the channel domain. <a href="#90" class="mim-tip-reference" title="Yan, Z., Bai, X., Yan, C., Wu, J., Li, Z., Xie, T., Peng, W., Yin, C., Li, X., Scheres, S. H. W., Shi, Y., Yan, N. <strong>Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution.</strong> Nature 517: 50-55, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25517095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25517095</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25517095[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/10.1038/nature14063" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25517095">Yan et al. (2015)</a> concluded that these structural features explain high ion conductance by ryanodine receptors and the long-range allosteric regulation of channel activities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25517095" 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>By in situ hybridization, <a href="#48" class="mim-tip-reference" title="MacLennan, D. H., Zorzato, F., Fujii, J., Otsu, K., Phillips, M., Lai, F. A., Meissner, G., Green, N. M., Willard, H. F., Britt, B. A., Worton, R. G., Korneluk, R. G. <strong>Cloning and localization of the human calcium release channel (ryanodine receptor) gene to the proximal long arm (cen-q13.2) of human chromosome 19. (Abstract)</strong> Am. J. Hum. Genet. 45 (suppl.): A205 only, 1989."None>MacLennan et al. (1989)</a> localized the RYR1 gene to chromosome 19cen-q13.2. By fluorescence in situ hybridization, <a href="#84" class="mim-tip-reference" title="Trask, B., Fertitta, A., Christensen, M., Youngblom, J., Bergmann, A., Copeland, A., de Jong, P., Mohrenweiser, H., Olsen, A., Carrano, A., Tynan, K. <strong>Fluorescence in situ hybridization mapping of human chromosome 19: cytogenetic band location of 540 cosmids and 70 genes or DNA markers.</strong> Genomics 15: 133-145, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432525</a>] [<a href="https://doi.org/10.1006/geno.1993.1021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8432525">Trask et al. (1993)</a> assigned the RYR1 gene to 19q13.1. <a href="#47" class="mim-tip-reference" title="MacKenzie, A. E., Korneluk, R. G., Zorzato, F., Fujii, J., Phillips, M., Iles, D., Wieringa, B., Leblond, S., Bailly, J., Willard, H. F., Duff, C., Worton, R. G., MacLennan, D. H. <strong>The human ryanodine receptor gene: its mapping to 19q13.1, placement in a chromosome 19 linkage group, and exclusion as the gene causing myotonic dystrophy.</strong> Am. J. Hum. Genet. 46: 1082-1089, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1971150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1971150</a>]" pmid="1971150">MacKenzie et al. (1990)</a> mapped the RYR1 gene to 19q13.1, distal to GPI (<a href="/entry/172400">172400</a>) and MAG (<a href="/entry/159460">159460</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1971150+8432525" 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>Using somatic cell hybrids, <a href="#35" class="mim-tip-reference" title="Harbitz, I., Chowdhary, B., Thomsen, P. D., Davies, W., Kaufmann, U., Kran, S., Gustavsson, I., Christensen, K., Hauge, J. G. <strong>Assignment of the porcine calcium release channel gene, a candidate for the malignant hyperthermia locus, to the 6p11-q21 segment of chromosome 6.</strong> Genomics 8: 243-248, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2174405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2174405</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90278-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2174405">Harbitz et al. (1990)</a> regionalized the porcine Ryr1 gene (termed CRC by them) to chromosome 6p11-q21. The authors noted homology of synteny with the genes on human chromosome 19. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2174405" 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="#10" class="mim-tip-reference" title="Cavanna, J. S., Greenfield, A. J., Johnson, K. J., Marks, A. R., Nadal-Ginard, B., Brown, S. D. M. <strong>Establishment of the mouse chromosome 7 region with homology to the myotonic dystrophy region of human chromosome 19q.</strong> Genomics 7: 12-18, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1970795/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1970795</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90513-t" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1970795">Cavanna et al. (1990)</a> demonstrated that the Ryr gene in the mouse maps to chromosome 7. By in situ hybridization, <a href="#51" class="mim-tip-reference" title="Mattei, M. G., Giannini, G., Moscatelli, F., Sorrentino, V. <strong>Chromosomal localization of murine ryanodine receptor genes RYR1, RYR2, and RYR3 by in situ hybridization.</strong> Genomics 22: 202-204, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7959768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7959768</a>] [<a href="https://doi.org/10.1006/geno.1994.1362" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7959768">Mattei et al. (1994)</a> mapped the mouse Ryr1 gene to 7A2-7A3. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7959768+1970795" 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><a href="#70" class="mim-tip-reference" title="Robinson, R., Carpenter, D., Shaw, M.-A., Halsall, J., Hopkins, P. <strong>Mutations in RYR1 in malignant hyperthermia and central core disease.</strong> Hum. Mutat. 27: 977-989, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16917943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16917943</a>] [<a href="https://doi.org/10.1002/humu.20356" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16917943">Robinson et al. (2006)</a> provided a detailed review of mutations in the RYR1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16917943" 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>Susceptibility to Malignant Hyperthermia</em></strong></p><p>
|
|
In several porcine breeds that exhibited inheritance of malignant hyperthermia (<a href="/entry/145600">145600</a>), <a href="#61" class="mim-tip-reference" title="Otsu, K., Khanna, V. K., Archibald, A. L., MacLennan, D. H. <strong>Cosegregation of porcine malignant hyperthermia and a probable causal mutation in the skeletal muscle ryanodine receptor gene in backcross families.</strong> Genomics 11: 744-750, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1774073/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1774073</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90083-q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1774073">Otsu et al. (1991)</a> and <a href="#29" class="mim-tip-reference" title="Fujii, J., Otsu, K., Zorzato, F., de Leon, S., Khanna, V. K., Weiler, J. E., O'Brien, P. J., MacLennan, D. H. <strong>Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia.</strong> Science 253: 448-451, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1862346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1862346</a>] [<a href="https://doi.org/10.1126/science.1862346" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1862346">Fujii et al. (1991)</a> identified a mutation in the Ryr1 gene (R615C). In 1 of 35 Canadian families with malignant hyperthermia, <a href="#31" class="mim-tip-reference" title="Gillard, E. F., Otsu, K., Fujii, J., Khanna, V. K., de Leon, S., Derdemezi, J., Britt, B. A., Duff, C. L., Worton, R. G., MacLennan, D. H. <strong>A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia.</strong> Genomics 11: 751-755, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1774074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1774074</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90084-r" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1774074">Gillard et al. (1991)</a> identified the same mutation, which is R614C (<a href="#0001">180901.0001</a>) in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1774073+1774074+1862346" 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 patients with malignant hyperthermia, <a href="#50" class="mim-tip-reference" title="Manning, B. M., Quane, K. A., Ording, H., Urwyler, A., Tegazzin, V., Lehane, M., O'Halloran, J., Hartung, E., Giblin, L. M., Lynch, P. J., Vaughan, P., Censier, K., Bendixen, D., Comi, G., Heytens, L., Monsieurs, K., Fagerlund, T., Wolz, W., Heffron, J. J. A., Muller, C. R., McCarthy, T. V. <strong>Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation.</strong> Am. J. Hum. Genet. 62: 599-609, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9497245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9497245</a>] [<a href="https://doi.org/10.1086/301748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9497245">Manning et al. (1998)</a> identified 4 adjacent mutations in the RYR1 gene: R2163C (<a href="#0010">180901.0010</a>), R2163H (<a href="#0011">180901.0011</a>), V2168M (<a href="#0013">180901.0013</a>), and T2206M (<a href="#0014">180901.0014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9497245" 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="Brandt, A., Schleithoff, L., Jurkat-Rott, K., Klingler, W., Baur, C., Lehmann-Horn, F. <strong>Screening of ryanodine receptor gene in 105 malignant hyperthermia families: novel mutations and concordance with the in vitro contracture test.</strong> Hum. Molec. Genet. 8: 2055-2062, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10484775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10484775</a>] [<a href="https://doi.org/10.1093/hmg/8.11.2055" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10484775">Brandt et al. (1999)</a> stated that 21 RYR1 mutations had been identified in families with malignant hyperthermia, 4 of which were also associated with central core myopathy. By screening for these 21 mutations in 105 MH families, including 10 families with central core disease (CCD) (CMYO1A; <a href="/entry/117000">117000</a>), phenotyped by the IVCT according to the European protocol, the authors determined the approximate mutation frequencies, with R614C (9%; <a href="#0001">180901.0001</a>) and G2434R (7%; <a href="#0007">180901.0007</a>) being the most common mutations. <a href="#7" class="mim-tip-reference" title="Brandt, A., Schleithoff, L., Jurkat-Rott, K., Klingler, W., Baur, C., Lehmann-Horn, F. <strong>Screening of ryanodine receptor gene in 105 malignant hyperthermia families: novel mutations and concordance with the in vitro contracture test.</strong> Hum. Molec. Genet. 8: 2055-2062, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10484775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10484775</a>] [<a href="https://doi.org/10.1093/hmg/8.11.2055" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10484775">Brandt et al. (1999)</a> also detected 2 novel mutations, each in a single pedigree. In the 109 individuals of the 25 families with RYR1 mutations, cosegregation between genetic result and IVCT was almost perfect. Only 3 genotypes were discordant with the IVCT phenotypes, suggesting a true sensitivity of 98.5% and a specificity of minimally 81.8% for this test. Screening of the transmembrane region of RYR1 did not yield a new mutation, confirming the cytosolic portion of the protein to be of main functional importance for pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10484775" 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="#72" class="mim-tip-reference" title="Sambuughin, N., McWilliams, S., de Bantel, A., Sivakumar, K., Nelson, T. E. <strong>Single-amino-acid deletion in the RYR1 gene, associated with malignant hyperthermia susceptibility and unusual contraction phenotype.</strong> Am. J. Hum. Genet. 69: 204-208, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11389482/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11389482</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11389482[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/10.1086/321270" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11389482">Sambuughin et al. (2001)</a> reported that malignant hyperthermia susceptibility (MHS) had been found to be associated with 30 different mutations in the RYR1 gene, all of which represent single-nucleotide changes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11389482" 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="#55" class="mim-tip-reference" title="Monnier, N., Kozak-Ribbens, G., Krivosic-Horber, R., Nivoche, Y., Qi, D., Kraev, N., Loke, J., Sharma, P., Tegazzin, V., Figarella-Branger, D., Romero, N., Mezin, P., Bendahan, D., Payen, J.-F., Depret, T., Maclennan, D. H., Lunardi, J. <strong>Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility.</strong> Hum. Mutat. 26: 413-425, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16163667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16163667</a>] [<a href="https://doi.org/10.1002/humu.20231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16163667">Monnier et al. (2005)</a> reported the results of correlation studies performed with molecular, pharmacologic, histologic, and functional data obtained from 176 families, 129 referred to as 'confirmed' and 46 as 'potential' MHS families. Extensive molecular analysis allowed them to identify a variant in 60% of the confirmed MHS families and resulted in the characterization of 11 new variants in the RYR1 gene. Most of the mutations clustered in the MH1 (52%) and MH2 (36%) domains of the RYR1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16163667" 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="#37" class="mim-tip-reference" title="Johnston, J. J., Dirksen, R. T., Girard, T., Gonsalves, S. G., Hopkins, P. M., Riazi, S., Saddic, L. A., Sambuughin, N., Saxena, R., Stowell, K., Weber, J., Rosenberg, H., Biesecker, L. G. <strong>Variant curation expert panel recommendations for RYR1 pathogenicity classifications in malignant hyperthermia susceptibility.</strong> Genet. Med. 23: 1288-1295, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33767344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33767344</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33767344[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/10.1038/s41436-021-01125-w" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33767344">Johnston et al. (2021)</a> reported an adaptation of the American College of Medical Genetics/Association for Molecular Pathology (ACMG/AMP) pathogenicity criteria by a variant curation expert panel for the classification of RYR1 variants in malignant hyperthermia susceptibility. Using the new criteria, 44 RYR1 gene mutations previously determined to be diagnostic by the European Malignant Hyperthermia Group (EMHG) were categorized: 29 were classified as pathogenic, 13 as likely pathogenic, and 2 as variants of unknown significance. <a href="#37" class="mim-tip-reference" title="Johnston, J. J., Dirksen, R. T., Girard, T., Gonsalves, S. G., Hopkins, P. M., Riazi, S., Saddic, L. A., Sambuughin, N., Saxena, R., Stowell, K., Weber, J., Rosenberg, H., Biesecker, L. G. <strong>Variant curation expert panel recommendations for RYR1 pathogenicity classifications in malignant hyperthermia susceptibility.</strong> Genet. Med. 23: 1288-1295, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33767344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33767344</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33767344[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/10.1038/s41436-021-01125-w" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33767344">Johnston et al. (2021)</a> concluded that use of the new criteria should allow for more consistent classification of RYR1 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33767344" 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 Congenital Myopathy 1A With Susceptibility to Malignant Hyperthermia</em></strong></p><p>
|
|
In affected members of a large multigenerational Canadian family with autosomal dominant congenital myopathy-1A (CMYO1A; <a href="/entry/117000">117000</a>) with central core disease on skeletal muscle biopsy (CCD) and susceptibility to malignant hyperthermia originally reported by <a href="#75" class="mim-tip-reference" title="Shuaib, A., Paasuke, R. T., Brownell, K. W. <strong>Central core disease: clinical features in 13 patients.</strong> Medicine 66: 389-396, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3626847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3626847</a>]" pmid="3626847">Shuaib et al. (1987)</a>, <a href="#92" class="mim-tip-reference" title="Zhang, Y., Chen, H. S., Khanna, V. K., De Leon, S., Phillips, M. S., Schappert, K., Britt, B. A., Brownell, A. K. W., MacLennan, D. H. <strong>A mutation in the human ryanodine receptor gene associated with central core disease.</strong> Nature Genet. 5: 46-50, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8220422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8220422</a>] [<a href="https://doi.org/10.1038/ng0993-46" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8220422">Zhang et al. (1993)</a> identified a heterozygous missense mutation in the RYR1 gene (R2435H; <a href="#0003">180901.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3626847+8220422" 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 2 Italian brothers (family 4T) with CMYO1A manifest as central core disease (CCD) on skeletal muscle biopsy, <a href="#65" class="mim-tip-reference" title="Quane, K. A., Healy, J. M. S., Keating, K. E., Manning, B. M., Couch, F. J., Palmucci, L. M., Doriguzzi, C., Fagerlund, T. H., Berg, K., Ording, H., Bendixen, D., Mortier, W., Linz, U., Muller, C. R., McCarthy, T. V. <strong>Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia.</strong> Nature Genet. 5: 51-55, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8220423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8220423</a>] [<a href="https://doi.org/10.1038/ng0993-51" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8220423">Quane et al. (1993)</a> identified a heterozygous missense mutation in the RYR1 gene (I403M; <a href="#0005">180901.0005</a>). The clinically unaffected father also carried the mutation; he did not undergo muscle biopsy. In 4 members of another Italian family (2T) with variable expression of CMYO1A and malignant hyperthermia, <a href="#65" class="mim-tip-reference" title="Quane, K. A., Healy, J. M. S., Keating, K. E., Manning, B. M., Couch, F. J., Palmucci, L. M., Doriguzzi, C., Fagerlund, T. H., Berg, K., Ording, H., Bendixen, D., Mortier, W., Linz, U., Muller, C. R., McCarthy, T. V. <strong>Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia.</strong> Nature Genet. 5: 51-55, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8220423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8220423</a>] [<a href="https://doi.org/10.1038/ng0993-51" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8220423">Quane et al. (1993)</a> identified a heterozygous mutation in the RYR1 gene (R163C; <a href="#0004">180901.0004</a>). Of note, <a href="#65" class="mim-tip-reference" title="Quane, K. A., Healy, J. M. S., Keating, K. E., Manning, B. M., Couch, F. J., Palmucci, L. M., Doriguzzi, C., Fagerlund, T. H., Berg, K., Ording, H., Bendixen, D., Mortier, W., Linz, U., Muller, C. R., McCarthy, T. V. <strong>Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia.</strong> Nature Genet. 5: 51-55, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8220423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8220423</a>] [<a href="https://doi.org/10.1038/ng0993-51" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8220423">Quane et al. (1993)</a> also identified the R163C mutation in a Danish family (D15) in which a mother and her 2 children had MHS without clinical signs of a myopathy and absence of cores on muscle biopsy. These findings demonstrated phenotypic variability, both within families and between families with the same mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8220423" 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="#46" class="mim-tip-reference" title="Lynch, P. J., Tong, J., Lehane, M., Mallet, A., Giblin, L., Heffron, J. J. A., Vaughan, P., Zafra, G., MacLennan, D. H., McCarthy, T. V. <strong>A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca(2+) release channel function and severe central core disease.</strong> Proc. Nat. Acad. Sci. 96: 4164-4169, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10097181/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10097181</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10097181[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/10.1073/pnas.96.7.4164" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10097181">Lynch et al. (1999)</a> studied a large Mexican kindred in which all affected members had a clinically severe and highly penetrant form of CMYO1A. Sequencing of the entire RYR1 cDNA in an affected member identified a single heterozygous mutation in the C-terminal transmembrane/luminal domain of the protein (<a href="#0012">180901.0012</a>). The introduction of this mutation into a recombinant RyR1 protein expressed in HEK293 cells resulted in loss of channel activation by caffeine and halothane and a significant reduction in ryanodine binding. These and additional findings, which pointed to a high basal activity of the mutant Ca(2+) channel, could explain the muscle weakness and muscle atrophy observed in CCD patients in this family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10097181" 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="#74" class="mim-tip-reference" title="Scacheri, P. C., Hoffman, E. P., Fratkin, J. D., Semino-Mora, C., Senchak, A., Davis, M. R., Laing, N. G., Vedanarayanan, V., Subramony, S. H. <strong>A novel ryanodine receptor gene mutation causing both cores and rods in congenital myopathy.</strong> Neurology 55: 1689-1696, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11113224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11113224</a>] [<a href="https://doi.org/10.1212/wnl.55.11.1689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11113224">Scacheri et al. (2000)</a> identified a heterozygous mutation in the RYR1 gene (<a href="#0030">180901.0030</a>) in affected members of a large family with CMYO1A. Skeletal muscle biopsies from 2 affected individuals showed the presence of central cores in over 85% of myofibers and nemaline rods in 5 to 25% of myofibers. <a href="#74" class="mim-tip-reference" title="Scacheri, P. C., Hoffman, E. P., Fratkin, J. D., Semino-Mora, C., Senchak, A., Davis, M. R., Laing, N. G., Vedanarayanan, V., Subramony, S. H. <strong>A novel ryanodine receptor gene mutation causing both cores and rods in congenital myopathy.</strong> Neurology 55: 1689-1696, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11113224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11113224</a>] [<a href="https://doi.org/10.1212/wnl.55.11.1689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11113224">Scacheri et al. (2000)</a> suggested that nemaline bodies may be a secondary feature in this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11113224" 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 5 members of a French family with CMYO1A, <a href="#58" class="mim-tip-reference" title="Monnier, N., Romero, N. B., Lerale, J., Nivoche, Y., Qi, D., MacLennan, D. H., Fardeau, M., Lunardi, J. <strong>An autosomal dominant congenital myopathy with cores and rods is associated with a neomutation in the RYR1 gene encoding the skeletal muscle ryanodine receptor.</strong> Hum. Molec. Genet. 9: 2599-2608, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11063719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11063719</a>] [<a href="https://doi.org/10.1093/hmg/9.18.2599" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11063719">Monnier et al. (2000)</a> identified a heterozygous missense mutation in the RYR1 gene (Y4796C; <a href="#0016">180901.0016</a>). The mutation occurs in the C-terminal channel-forming domain of the RYR1 protein. Expression of the mutant RYR1 cDNA in rabbit HEK293 cells produced channels with increased caffeine sensitivity, cells with increased resting cytoplasmic Ca(2+) levels, and a significantly reduced maximal level of Ca(2+) release, suggesting an increased rate of Ca(2+) leakage in the mutant channel. The authors hypothesized that the resulting chronic elevation in myoplasmic Ca(2+) concentration may be responsible for the severe phenotype in this family. Haplotype analysis indicated that the mutation arose de novo in the proband. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11063719" 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 affected members of 16 unrelated families with CMYO1A, <a href="#57" class="mim-tip-reference" title="Monnier, N., Romero, N. B., Lerale, J., Landrieu, P., Nivoche, Y., Fardeau, M., Lunardi, J. <strong>Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor.</strong> Hum. Molec. Genet. 10: 2581-2592, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709545</a>] [<a href="https://doi.org/10.1093/hmg/10.22.2581" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11709545">Monnier et al. (2001)</a> identified 12 different missense mutations in the C-terminal domain of RYR1 (see, e.g., I4898T, <a href="#0012">180901.0012</a>; V2168M, <a href="#0013">180901.0013</a>; a 9-bp del, <a href="#0018">180901.0018</a>; R4861H, <a href="#0019">180901.0019</a>; and R4893W, <a href="#0044">180901.0044</a>). Since the muscle symptoms in the families suggested a defect in Ca(2+) homeostasis, the authors sequenced exons in the C-terminal channel-forming domain of RYR1, which is involved in Ca(2+) movement. V2168M occurred in exon 39, but all of the other mutations occurred in exons 91 through 102. Four de novo mutations were found, indicating that de novo mutations in RYR1 are not rare and may confound genetic studies of families that present with congenital myopathies. Functional studies of the mutations were not performed. Molecular modeling based on a 4-transmembrane domain model suggested that the mutations concentrated mostly in the myoplasmic and luminal loops linking, respectively, transmembrane domains T1 and T2 or T3 and T4 of RYR1 and may therefore affect the excitation-contraction process in skeletal muscle. The patients were ascertained from a cohort of 34 families with congenital myopathy associated with central cores on muscle biopsy who underwent genetic analysis; RYR1 mutations were found in 47% of families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709545" 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="#81" class="mim-tip-reference" title="Tilgen, N., Zorzato, F., Halliger-Keller, B., Muntoni, F., Sewry, C., Palumucci, L. M., Schneider, C., Hauser, E., Lehmann-Horn, F., Muller, C. R., Treves, S. <strong>Identification of four novel mutations in the C-terminal membrane spanning domain of the ryanodine receptor 1: association with central core disease and alteration of calcium homeostasis.</strong> Hum. Molec. Genet. 10: 2879-2887, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741831</a>] [<a href="https://doi.org/10.1093/hmg/10.25.2879" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11741831">Tilgen et al. (2001)</a> screened the C-terminal domain of the RYR1 gene for mutations in 50 European patients diagnosed clinically and/or histologically as having congenital myopathy with central cores on biopsy (central core disease, CCD). Four novel missense mutations (see, e.g., <a href="#0012">180901.0012</a> and <a href="#0019">180901.0019</a>) were identified in 13 of 25 index patients. The mutations clustered in exons 101 and 102 and replaced conserved amino acids. Lymphoblasts derived from patients carrying these C-terminal RYR1 mutations exhibited a release of calcium from intracellular stores in the absence of any pharmacologic activators of RYR; significantly smaller thapsigargin-sensitive intracellular calcium stores, compared to lymphoblasts from control individuals; and a normal sensitivity of the calcium release to the RYR inhibitor dantrolene. The authors suggested that the C-terminal domain of RYR1 may be a hotspot for mutations leading to the CCD phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11741831" 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="#95" class="mim-tip-reference" title="Zorzato, F., Yamaguchi, N., Xu, L., Meissner, G., Muller, C. R., Pouliquin, P., Muntoni, F., Sewry, C., Girard, T., Treves, S. <strong>Clinical and functional effects of a deletion in a COOH-terminal lumenal loop of the skeletal muscle ryanodine receptor.</strong> Hum. Molec. Genet. 12: 379-388, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12566385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12566385</a>] [<a href="https://doi.org/10.1093/hmg/ddg032" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12566385">Zorzato et al. (2003)</a> identified a patient with severe CCD and her mother with mild CCD who were both heterozygous for a deletion (amino acids 4863-4869; <a href="#0024">180901.0024</a>) in the pore-forming region of the sarcoplasmic reticulum calcium release channel. The deleted amino acids form part of the luminal loop connecting membrane-spanning segments M8 and M10 and are conserved in all known vertebrate RYR1 isoforms. Lymphoblastoid cells carrying the RYR1 deletion exhibited an 'unprompted' calcium release from intracellular stores, resulting in significantly smaller thapsigargin-sensitive intracellular Ca(2+) stores compared with lymphoblastoid cells from controls. Blocking the RYR1 with dantrolene restored the intracellular calcium stores to levels similar to those found in controls. Single-channel and [3H]ryanodine-binding measurements in HEK293 cells heterologously expressing mutant channels revealed a reduced ion conductance and loss of ryanodine binding and regulation by Ca(2+). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12566385" 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 11 patients from 4 unrelated families with CMYO1A, <a href="#68" class="mim-tip-reference" title="Quinlivan, R. M., Muller, C. R., Davis, M., Laing, N. G., Evans, G. A., Dwyer, J., Dove, J., Roberts, A. P., Sewry, C. A. <strong>Central core disease: clinical, pathological, and genetic features.</strong> Arch. Dis. Child. 88: 1051-1055, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14670767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14670767</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14670767[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/adc.88.12.1051" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14670767">Quinlivan et al. (2003)</a> identified heterozygous mutations in the RYR1 gene (see, e.g., R4861H, <a href="#0019">180901.0019</a>; R4893W, <a href="#0044">180901.0044</a>; and Y4864C, <a href="#0045">180901.0045</a>). All mutations occurred in region 3 of the RYR1 gene. The mutation was inherited in an autosomal dominant pattern in 3 families (families A, B, and C), whereas the mutation occurred de novo in the proband from family D. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14670767" 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 4 unrelated Japanese patients with CMYO1A and a pathologic diagnosis of congenital neuromuscular disease with uniform type 1 fiber (CNMDU1), <a href="#73" class="mim-tip-reference" title="Sato, I., Wu, S., Ibarra, M. C. A., Hayashi, Y. K., Fujita, H., Tojo, M., Oh, S. J., Nonaka, I., Noguchi, S., Nishino, I. <strong>Congenital neuromuscular disease with uniform type 1 fiber and RYR1 mutation.</strong> Neurology 70: 114-122, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17538032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17538032</a>] [<a href="https://doi.org/10.1212/01.wnl.0000269792.63927.86" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17538032">Sato et al. (2008)</a> identified heterozygous mutations in the RYR1 gene (see, e.g., <a href="#0019">180901.0019</a>; <a href="#0033">180901.0033</a>-<a href="#0034">180901.0034</a>). The father of 1 patient had the same mutation as his son (<a href="#0033">180901.0033</a>) and was diagnosed with CCD (<a href="#89" class="mim-tip-reference" title="Wu, S., Ibarra M, C. A., Malicdan, M. C. V., Murayama, K., Ichihara, Y., Kikuchi, H., Nonaka, I., Noguchi, S., Hayashi, Y. K., Nishino, I. <strong>Central core disease is due to RYR1 mutations in more than 90% of patients.</strong> Brain 129: 1470-1480, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16621918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16621918</a>] [<a href="https://doi.org/10.1093/brain/awl077" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16621918">Wu et al., 2006</a>; <a href="#83" class="mim-tip-reference" title="Tojo, M., Ozawa, M., Nonaka, I. <strong>Central core disease and congenital neuromuscular disease with uniform type 1 fibers in one family.</strong> Brain Dev. 22: 262-264, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10838116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10838116</a>] [<a href="https://doi.org/10.1016/s0387-7604(00)00108-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10838116">Tojo et al., 2000</a>), indicating that RYR1 mutations can cause variable findings on skeletal muscle biopsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17538032+16621918+10838116" 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 Recessive Congenital Myopathy 1B</em></strong></p><p>
|
|
In affected members of a consanguineous Algerian family with autosomal recessive congenital myopathy-1B (CMYO1B; <a href="/entry/255320">255320</a>) characterized by the presence of multiple, short-length core lesions (minicores) on skeletal muscle biopsy, <a href="#28" class="mim-tip-reference" title="Ferreiro, A., Monnier, N., Romero, N. B., Leroy, J.-P., Bonnemann, C., Haenggeli, C.-A., Straub, V., Voss, W. D., Nivoche, Y., Jungbluth, H., Lemainque, A., Voit, T., Lunardi, J., Fardeau, M., Guicheney, P. <strong>A recessive form of central core disease, transiently presenting as multi-minicore disease, is associated with a homozygous mutation in the ryanodine receptor type 1 gene.</strong> Ann. Neurol. 51: 750-759, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12112081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12112081</a>] [<a href="https://doi.org/10.1002/ana.10231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12112081">Ferreiro et al. (2002)</a> identified a homozygous missense mutation in the RYR1 gene (P3527S; <a href="#0021">180901.0021</a>). Three children in the family presented in infancy with moderate weakness predominant in axial muscles, pelvic girdle, and hands, joint hyperlaxity, and multiple minicores on skeletal muscle biopsy. New muscle biopsies from the 3 patients in adulthood demonstrated central core disease with rods; no cores were found in the healthy parents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12112081" 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 a 19-year-old girl, born of consanguineous parents (family 1), with CMYO1B, <a href="#39" class="mim-tip-reference" title="Jungbluth, H., Muller, C. R., Halliger-Keller, B., Brockington, M., Brown, S. C., Feng, L., Chattopadhyay, A., Mercuri, E., Manzur, A. Y., Ferreiro, A., Laing, N. G., Davis, M. R., Roper, H. P., Dubowitz, V., Bydder, G., Sewry, C. A., Muntoni, F. <strong>Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores.</strong> Neurology 59: 284-287, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12136074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12136074</a>] [<a href="https://doi.org/10.1212/wnl.59.2.284" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12136074">Jungbluth et al. (2002)</a> identified a homozygous missense mutation in the RYR1 gene (V4849I; <a href="#0022">180901.0022</a>). In a 9-year-old girl, born of consanguineous parents, with autosomal recessive CMYO1B and central core disease on muscle biopsy, <a href="#43" class="mim-tip-reference" title="Kossugue, P. M., Paim, J. F., Navarro, M. M., Silva, H. C., Pavanello, R. C. M., Gurgel-Giannetti, J., Zatz, M., Vainzof, M. <strong>Central core disease due to recessive mutations in RYR1 gene: is it more common than described?</strong> Muscle Nerve 35: 670-674, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17226826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17226826</a>] [<a href="https://doi.org/10.1002/mus.20715" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17226826">Kossugue et al. (2007)</a> identified a homozygous V4849I substitution in the RYR1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17226826+12136074" 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="#54" class="mim-tip-reference" title="Monnier, N., Ferreiro, A., Marty, I., Labarre-Vila, A., Mezin, P., Lunardi, J. <strong>A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia.</strong> Hum. Molec. Genet. 12: 1171-1178, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12719381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12719381</a>] [<a href="https://doi.org/10.1093/hmg/ddg121" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12719381">Monnier et al. (2003)</a> and <a href="#40" class="mim-tip-reference" title="Jungbluth, H., Zhou, H., Hartley, L., Halliger-Keller, B., Messina, S., Longman, C., Brockington, M., Robb, S. A., Straub, V., Voit, T., Swash, M., Ferreiro, A., Bydder, G., Sewry, C. A., Muller, C., Muntoni, F. <strong>Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.</strong> Neurology 65: 1930-1935, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16380615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16380615</a>] [<a href="https://doi.org/10.1212/01.wnl.0000188870.37076.f2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16380615">Jungbluth et al. (2005)</a> identified biallelic mutations in the RYR1 gene (see, e.g., <a href="#0025">180901.0025</a>-<a href="#0029">180901.0029</a>) in patients with CMYO1B manifest as minicore myopathy with external ophthalmoplegia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12719381+16380615" 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="#56" class="mim-tip-reference" title="Monnier, N., Marty, I., Faure, J., Castiglioni, C., Desnuelle, C., Sacconi, S., Estournet, B., Ferreiro, A., Romero, N., Laquerriere, A., Lazaro, L., Martin, J.-J., Morava, E., Rossi, A., Van der Kooi, A., de Visser, M., Verschuuren, C., Lunardi, J. <strong>Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.</strong> Hum. Mutat. 29: 670-678, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18253926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18253926</a>] [<a href="https://doi.org/10.1002/humu.20696" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18253926">Monnier et al. (2008)</a> reported a 9-year-old Dutch boy with a severe autosomal recessive myopathy with ptosis and facial diplegia associated with compound heterozygous mutations in the RYR1 gene: V4849I and a 4-bp insertion (<a href="#0032">180901.0032</a>). <a href="#56" class="mim-tip-reference" title="Monnier, N., Marty, I., Faure, J., Castiglioni, C., Desnuelle, C., Sacconi, S., Estournet, B., Ferreiro, A., Romero, N., Laquerriere, A., Lazaro, L., Martin, J.-J., Morava, E., Rossi, A., Van der Kooi, A., de Visser, M., Verschuuren, C., Lunardi, J. <strong>Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.</strong> Hum. Mutat. 29: 670-678, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18253926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18253926</a>] [<a href="https://doi.org/10.1002/humu.20696" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18253926">Monnier et al. (2008)</a> postulated that since the patient had a hypomorphic frameshift RYR1 allele, the resultant phenotype was more severe compared to those patients with homozygous V4849I mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18253926" 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 17 patients, all from unrelated nonconsanguineous families, with CMYO1B and a clinicopathologic diagnosis of centronuclear myopathy (CNM), <a href="#88" class="mim-tip-reference" title="Wilmshurst, J. M., Lillis, S., Zhou, H., Pillay, K., Henderson, H., Kress, W., Muller, C. R., Ndondo, A., Cloke, V., Cullup, T., Bertini, E., Boennemann, C., and 10 others. <strong>RYR1 mutations are a common cause of congenital myopathies with central nuclei.</strong> Ann. Neurol. 68: 717-726, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20839240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20839240</a>] [<a href="https://doi.org/10.1002/ana.22119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20839240">Wilmshurst et al. (2010)</a> identified mutations in the RYR1 gene (see, e.g., <a href="#0035">180901.0035</a>-<a href="#0037">180901.0037</a>). Compound heterozygosity for a nonsense and missense mutation was found in all except 3 patients, in whom a second pathogenic allele could not be found. The phenotype was characterized by onset at birth, neonatal hypotonia and weakness, delayed motor development, external ophthalmoplegia, and bulbar involvement. In addition to central nuclei, prominent histopathologic findings included multiple internalized nuclei, type 1 fiber predominance and hypotrophy, relative type 2 hypertrophy, and oxidative abnormalities in electron microscopic analysis, although frank cores were not typically seen. Twelve of the patients were from South Africa, and haplotype analysis suggested founder effects for some of the mutant alleles. The 17 patients were ascertained from a larger group of 24 patients with a diagnosis of CNM, indicating that RYR1 mutations can account for this subtype of myopathy. <a href="#88" class="mim-tip-reference" title="Wilmshurst, J. M., Lillis, S., Zhou, H., Pillay, K., Henderson, H., Kress, W., Muller, C. R., Ndondo, A., Cloke, V., Cullup, T., Bertini, E., Boennemann, C., and 10 others. <strong>RYR1 mutations are a common cause of congenital myopathies with central nuclei.</strong> Ann. Neurol. 68: 717-726, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20839240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20839240</a>] [<a href="https://doi.org/10.1002/ana.22119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20839240">Wilmshurst et al. (2010)</a> postulated that disorder resulted from disturbed assembly and/or malfunction of the excitation-contraction machinery. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20839240" 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 (8.3%) of 36 families with CMYO1B manifest as fetal akinesia deformation/lethal pterygium syndrome, <a href="#53" class="mim-tip-reference" title="McKie, A. B., Alsaedi, A., Vogt, J., Stuurman, K. E., Weiss, M. M., Shakeel, H., Tee, L., Morgan, N. V., Nikkels, P. G. J., van Haaften, G., Park, S.-M., van der Smagt, J. J., Bugiani, M., Maher, E. R. <strong>Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome.</strong> Acta Neuropath. Commun. 2: 148, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25476234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25476234</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25476234[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/10.1186/s40478-014-0148-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25476234">McKie et al. (2014)</a> identified 3 different homozygous nonsense or intragenic deletion mutations in the RYR1 gene (<a href="#0039">180901.0039</a>-<a href="#0041">180901.0041</a>). <a href="#53" class="mim-tip-reference" title="McKie, A. B., Alsaedi, A., Vogt, J., Stuurman, K. E., Weiss, M. M., Shakeel, H., Tee, L., Morgan, N. V., Nikkels, P. G. J., van Haaften, G., Park, S.-M., van der Smagt, J. J., Bugiani, M., Maher, E. R. <strong>Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome.</strong> Acta Neuropath. Commun. 2: 148, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25476234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25476234</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25476234[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/10.1186/s40478-014-0148-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25476234">McKie et al. (2014)</a> suggested that RYR1 mutation analysis should be performed in cases with severe early lethal fetal akinesia even in the absence of specific histopathologic indicators of RYR1-related disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25476234" 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>King-Denborough Syndrome</em></strong></p><p>
|
|
In a patient with King-Denborough syndrome (KDS; <a href="/entry/619542">619542</a>), <a href="#13" class="mim-tip-reference" title="D'Arcy, C. E., Bjorksten, A., Yiu, E. M., Bankier, A., Gillies, R., McLean, C. A., Shield, L. K., Ryan, M. M. <strong>King-Denborough syndrome caused by a novel mutation in the ryanodine receptor gene.</strong> Neurology 71: 776-777, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18765655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18765655</a>] [<a href="https://doi.org/10.1212/01.wnl.0000324929.33780.2f" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18765655">D'Arcy et al. (2008)</a> identified a heterozygous mutation in the RYR1 gene (<a href="/entry/180902#0038">180902.0038</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18765655" 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 direct RYR1 sequencing, <a href="#15" class="mim-tip-reference" title="Dowling, J. J., Lillis S., Amburgey, K., Zhou, H., Al-Sarraj, S., Buk, S. J. A., Wraige, E., Chow, G., Abbs, S., Leber, S., Lachlan, K., Baralle, D., Taylor, A., Sewry, C., Muntoni, F., Jungbluth, H. <strong>King-Denborough syndrome with and without mutations in the skeletal muscle ryanodine receptor (RYR1) gene.</strong> Neuromusc. Disord. 21: 420-427, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21514828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21514828</a>] [<a href="https://doi.org/10.1016/j.nmd.2011.03.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21514828">Dowling et al. (2011)</a> identified heterozygous missense mutations in 4 patients with KDS, a 6-year-old boy (T2203M; <a href="#0014">180901.0014</a>) and 3 members of 1 family (R2452W; <a href="#0042">180901.0042</a>). In a patient with severe kyphoscoliosis, moderate proximal weakness, and distal joint laxity, <a href="#15" class="mim-tip-reference" title="Dowling, J. J., Lillis S., Amburgey, K., Zhou, H., Al-Sarraj, S., Buk, S. J. A., Wraige, E., Chow, G., Abbs, S., Leber, S., Lachlan, K., Baralle, D., Taylor, A., Sewry, C., Muntoni, F., Jungbluth, H. <strong>King-Denborough syndrome with and without mutations in the skeletal muscle ryanodine receptor (RYR1) gene.</strong> Neuromusc. Disord. 21: 420-427, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21514828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21514828</a>] [<a href="https://doi.org/10.1016/j.nmd.2011.03.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21514828">Dowling et al. (2011)</a> identified heterozygosity for an S2776F mutation in the RYR1 gene; however, her father, who also had the mutation, was asymptomatic. <a href="#15" class="mim-tip-reference" title="Dowling, J. J., Lillis S., Amburgey, K., Zhou, H., Al-Sarraj, S., Buk, S. J. A., Wraige, E., Chow, G., Abbs, S., Leber, S., Lachlan, K., Baralle, D., Taylor, A., Sewry, C., Muntoni, F., Jungbluth, H. <strong>King-Denborough syndrome with and without mutations in the skeletal muscle ryanodine receptor (RYR1) gene.</strong> Neuromusc. Disord. 21: 420-427, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21514828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21514828</a>] [<a href="https://doi.org/10.1016/j.nmd.2011.03.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21514828">Dowling et al. (2011)</a> concluded that the S2776F mutation was probably pathogenic but not sufficient to cause the patient's phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21514828" 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 a 2-year-old boy with KDS, <a href="#38" class="mim-tip-reference" title="Joseph, M. R., Theroux, M. C., Mooney, J. J., Falitz, S., Brandom, B. W., Byler, D. L. <strong>Intraoperative presentation of malignant hyperthermia (confirmed by RYR1 gene mutation, c.7522C-T; p.R2508C) leads to diagnosis of King-Denborough syndrome in a child with hypotonia and dysmorphic features: a case report.</strong> A. A. Case Rep. 8: 55-57, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27918309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27918309</a>] [<a href="https://doi.org/10.1213/XAA.0000000000000421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27918309">Joseph et al. (2017)</a> identified a heterozygous missense mutation in the RYR1 gene (R2508C; <a href="#0043">180901.0043</a>). Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27918309" 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="genotypePhenotypeCorrelations" class="mim-anchor"></a>
|
|
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGenotypePhenotypeCorrelationsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#50" class="mim-tip-reference" title="Manning, B. M., Quane, K. A., Ording, H., Urwyler, A., Tegazzin, V., Lehane, M., O'Halloran, J., Hartung, E., Giblin, L. M., Lynch, P. J., Vaughan, P., Censier, K., Bendixen, D., Comi, G., Heytens, L., Monsieurs, K., Fagerlund, T., Wolz, W., Heffron, J. J. A., Muller, C. R., McCarthy, T. V. <strong>Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation.</strong> Am. J. Hum. Genet. 62: 599-609, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9497245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9497245</a>] [<a href="https://doi.org/10.1086/301748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9497245">Manning et al. (1998)</a> tabulated the 17 mutations that had been identified in the RYR1 gene in families with MHS and CCD. They estimated that the 4 novel mutations they found accounted for approximately 11% of MH cases. The 13 that had been identified before their study were located in 2 regions, the N-terminal and central regions. Their study and that of others indicated that the gene segment 6400-6700 is a mutation hotspot. Two different amino acid substitutions had been identified in each of 3 codons: 614, 2163, and 2458. Correlation analysis of IVCT data available for pedigrees bearing these 17 RYR1 mutations showed an exceptionally good correlation between caffeine threshold and tension values, whereas no correlation was observed between halothane threshold and tension values. The findings indicated that assessment of recombinant individuals on the basis of caffeine response is justified, whereas assessment on the basis of halothane response may be problematic, and suggested a link between the caffeine threshold and tension values and the MH/CCD phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9497245" 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="#52" class="mim-tip-reference" title="McCarthy, T. V., Quane, K. A., Lynch, P. J. <strong>Ryanodine receptor mutations in malignant hyperthermia and central core disease.</strong> Hum. Mutat. 15: 410-417, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10790202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10790202</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(200005)15:5<410::AID-HUMU2>3.0.CO;2-D" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10790202">McCarthy et al. (2000)</a> noted that the majority of RYR1 mutations appeared to be clustered in the N-terminal amino acid residues 35-614 (referred to as the MH/CCD region-1) and the centrally located residues 2163-2458 (MH/CCD region-2). The only mutation identified outside of these regions was a single mutation associated with a severe form of CCD in the highly conserved C terminus of the gene, I4898T (<a href="#0012">180901.0012</a>). All of the RYR1 mutations result in amino acid substitutions in the myoplasmic portion of the protein, with the exception of the mutation in the C terminus, which resides in the luminal/transmembrane region. The likely deciding factors in determining whether a particular RYR1 mutation results in MHS alone or MHS and CCD are sensitivity of the RYR1 mutant proteins to agonists; the level of abnormal channel-gating caused by the mutation; the consequential decrease in the size of the releasable calcium store and increase in resting concentration of calcium; and the level of compensation achieved by the muscle with respect to maintaining calcium homeostasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10790202" 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="#71" class="mim-tip-reference" title="Robinson, R. L., Brooks, C., Brown, S. L., Ellis, F. R., Halsall, P. J., Quinnell, R. J., Shaw, M.-A., Hopkins, P. M. <strong>RYR1 mutations causing central core disease are associated with more severe malignant hyperthermia in vitro contracture test phenotypes.</strong> Hum. Mutat. 20: 88-97, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12124989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12124989</a>] [<a href="https://doi.org/10.1002/humu.10098" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12124989">Robinson et al. (2002)</a> stated that 15 RYR1 N-terminal mutations are considered causative of MHS, and that 5 of these are also associated with CCD. In an extensive U.K. population survey, they detected 8 of these 15 mutations in 85 of 297 (29%) unrelated MH susceptibility cases, with G2434R (<a href="#0007">180901.0007</a>) detected in 53 cases (18%). R163C (<a href="#0004">180901.0004</a>), R2163H (<a href="#0011">180901.0011</a>), and R2435H (<a href="#0003">180901.0003</a>), RYR1 mutations associated with both CCD and MH, had more severe caffeine and halothane response phenotypes than those associated with MH alone. Mutations near the N terminus (R163C; G341R, <a href="#0006">180901.0006</a>) had a relatively greater effect on response to caffeine than halothane, with a significantly increased caffeine:halothane tension ratio compared to G2434R of the central domain. All phenotypes were more severe in males than females, and were also affected by muscle specimen size and viability. Discordance between RYR1 genotype and IVCT phenotype was observed in 7 families (9 individuals), with 5 false-positives and 4 false-negatives. The clinical and genetic data in this study demonstrated that RYR1 mutations involved in CCD are those associated with 1 end of the spectrum of MH IVCT phenotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12124989" 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="#16" class="mim-tip-reference" title="Ducreux, S., Zorzato, F., Muller, C., Sewry, C., Muntoni, F., Quinlivan, R., Restagno, G., Girard, T., Treves, S. <strong>Effect of ryanodine receptor mutations on interleukin-6 release and intracellular calcium homeostasis in human myotubes from malignant hyperthermia-susceptible individuals and patients affected by central core disease.</strong> J. Biol. Chem. 279: 43838-43846, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15299003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15299003</a>] [<a href="https://doi.org/10.1074/jbc.M403612200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15299003">Ducreux et al. (2004)</a> found that cultured human myotubes with the I4898T mutation in the RYR1 gene (<a href="#0012">180901.0012</a>), which is in the C-terminal hydrophobic membrane-spanning region of the protein and causes CCD, had a 4-fold increase in background levels of IL6 in the absence of RYR1 activation compared to controls; cells with the V2168M (<a href="#0013">180901.0013</a>) mutation, which causes MHS, had background IL6 levels similar to control cells. In addition, cells with the CCD mutation had significantly less agonist-induced calcium release from intracellular stores compared to control cells or MHS cells. The findings indicated that mutations in the C-terminal domain reduce the amount of calcium released via the RYR1 channel, resulting in altered excitation-contraction coupling. Release of IL6, an inflammatory and pyrogenic cytokine, may affect signaling pathways responsible for muscle fiber abnormalities in CCD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15299003" 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="#45" class="mim-tip-reference" title="Lyfenko, A. D., Goonasekera, S. A., Dirksen, R. T. <strong>Dynamic alterations in myoplasmic Ca(2+) in malignant hyperthermia and central core disease.</strong> Biochem. Biophys. Res. Commun. 322: 1256-1266, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15336973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15336973</a>] [<a href="https://doi.org/10.1016/j.bbrc.2004.08.031" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15336973">Lyfenko et al. (2004)</a> reviewed the dynamic alterations in myoplasmic calcium metabolism in disorders caused by mutation in the RYR1 gene, and discussed molecular mechanisms by which these genetic defects lead to distinct clinical and histopathologic manifestations. <a href="#6" class="mim-tip-reference" title="Benkusky, N. A., Farrell, E. F., Valdivia, H. H. <strong>Ryanodine receptor channelopathies.</strong> Biochem. Biophys. Res. Commun. 322: 1280-1285, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15336975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15336975</a>] [<a href="https://doi.org/10.1016/j.bbrc.2004.08.033" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15336975">Benkusky et al. (2004)</a> reviewed RYR1 and RYR2 mutations and their role in muscle and heart disease, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15336973+15336975" 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="#42" class="mim-tip-reference" title="Klein, A., Lillis, S., Munteanu, I., Scoto, M., Zhou, H., Quinlivan, R., Straub, V., Manzur, A. Y., Roper, H., Jeannet, P-Y., Rakowicz, W., Jones, D. H., and 20 others. <strong>Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.</strong> Hum. Mutat. 33: 981-988, 2012. Note: Erratum: Hum. Mutat. 33: 1310, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22473935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22473935</a>] [<a href="https://doi.org/10.1002/humu.22056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22473935">Klein et al. (2012)</a> noted that dominant mutations involved in congenital myopathy-1A (CMYO1A; <a href="/entry/117000">117000</a>) are mostly confined to the C-terminal region of the gene, particularly region 3, whereas mutations involved in MHS are mostly detected in regions 1 and 2 within the N terminal. Most dominant mutations are missense. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22473935" 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="populationGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimPopulationGeneticsFold" id="mimPopulationGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimPopulationGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimPopulationGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#52" class="mim-tip-reference" title="McCarthy, T. V., Quane, K. A., Lynch, P. J. <strong>Ryanodine receptor mutations in malignant hyperthermia and central core disease.</strong> Hum. Mutat. 15: 410-417, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10790202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10790202</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(200005)15:5<410::AID-HUMU2>3.0.CO;2-D" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10790202">McCarthy et al. (2000)</a> pointed out that the RYR1 G341R mutation (<a href="#0006">180901.0006</a>) is present in about 6% of Irish/English/French families, but is rare in northern Europe. The R614C mutation (<a href="#0001">180901.0001</a>) is more common in German families (9%), while the V2168M (<a href="#0013">180901.0013</a>) mutation is common in Swiss families but relatively rare otherwise. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10790202" 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="#55" class="mim-tip-reference" title="Monnier, N., Kozak-Ribbens, G., Krivosic-Horber, R., Nivoche, Y., Qi, D., Kraev, N., Loke, J., Sharma, P., Tegazzin, V., Figarella-Branger, D., Romero, N., Mezin, P., Bendahan, D., Payen, J.-F., Depret, T., Maclennan, D. H., Lunardi, J. <strong>Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility.</strong> Hum. Mutat. 26: 413-425, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16163667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16163667</a>] [<a href="https://doi.org/10.1002/humu.20231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16163667">Monnier et al. (2005)</a> found that the RYR1 R614C mutation is the most prevalent mutation in French families with MHS, whereas it is poorly represented in affected families from the U.K. In contrast, the G2434R (<a href="#0007">180901.0007</a>) and V2168M (<a href="#0013">180901.0013</a>) mutations, which are the most prevalent in MHS families from the U.K. (<a href="#71" class="mim-tip-reference" title="Robinson, R. L., Brooks, C., Brown, S. L., Ellis, F. R., Halsall, P. J., Quinnell, R. J., Shaw, M.-A., Hopkins, P. M. <strong>RYR1 mutations causing central core disease are associated with more severe malignant hyperthermia in vitro contracture test phenotypes.</strong> Hum. Mutat. 20: 88-97, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12124989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12124989</a>] [<a href="https://doi.org/10.1002/humu.10098" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12124989">Robinson et al., 2002</a>) and Switzerland (<a href="#32" class="mim-tip-reference" title="Girard, T., Urwyler, A., Censier, K., Mueller, C. R., Zorzato, F., Treves, S. <strong>Genotype-phenotype comparison of the Swiss malignant hyperthermia population.</strong> Hum. Mutat. 18: 357-358, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11668625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11668625</a>] [<a href="https://doi.org/10.1002/humu.1203" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11668625">Girard et al., 2001</a>), respectively, are present at a much lower level in affected French families. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12124989+11668625+16163667" 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>In several porcine breeds exhibiting inheritance of malignant hyperthermia, <a href="#61" class="mim-tip-reference" title="Otsu, K., Khanna, V. K., Archibald, A. L., MacLennan, D. H. <strong>Cosegregation of porcine malignant hyperthermia and a probable causal mutation in the skeletal muscle ryanodine receptor gene in backcross families.</strong> Genomics 11: 744-750, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1774073/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1774073</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90083-q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1774073">Otsu et al. (1991)</a> and <a href="#29" class="mim-tip-reference" title="Fujii, J., Otsu, K., Zorzato, F., de Leon, S., Khanna, V. K., Weiler, J. E., O'Brien, P. J., MacLennan, D. H. <strong>Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia.</strong> Science 253: 448-451, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1862346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1862346</a>] [<a href="https://doi.org/10.1126/science.1862346" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1862346">Fujii et al. (1991)</a> identified a 1843C-T transition in the RYR1 gene, resulting in an arg615-to-cys (R615C) substitution. The same mutation was found in 5 major breeds (see <a href="#36" class="mim-tip-reference" title="Harbitz, I., Kristensen, T., Bosnes, M., Kran, S., Davies, W. <strong>DNA sequence of the skeletal muscle calcium release channel cDNA and verification of the arg615-to-cys615 mutation, associated with porcine malignant hyperthermia, in Norwegian Landrace pigs.</strong> Animal Genet. 23: 395-402, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1329581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1329581</a>] [<a href="https://doi.org/10.1111/j.1365-2052.1992.tb02157.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1329581">Harbitz et al. (1992)</a> for a sixth) of lean, heavily muscled swine, and haplotyping suggested that the mutation in all had a common origin, demonstrating a founder effect in these animals. <a href="#29" class="mim-tip-reference" title="Fujii, J., Otsu, K., Zorzato, F., de Leon, S., Khanna, V. K., Weiler, J. E., O'Brien, P. J., MacLennan, D. H. <strong>Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia.</strong> Science 253: 448-451, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1862346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1862346</a>] [<a href="https://doi.org/10.1126/science.1862346" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1862346">Fujii et al. (1991)</a> suggested that the mutation had been selected for by breeders because it was associated with lean and heavy muscles. The porcine R615C mutation corresponds to the R614C mutation identified in humans with malignant hyperthermia (<a href="#0001">180901.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1774073+1329581+1862346" 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="#78" class="mim-tip-reference" title="Takeshima, H., Iino, M., Takekura, H., Nishi, M., Kuno, J., Minowa, O., Takano, H., Noda, T. <strong>Excitation-contraction uncoupling and muscular degeneration in mice lacking functional skeletal muscle ryanodine-receptor gene.</strong> Nature 369: 556-559, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7515481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7515481</a>] [<a href="https://doi.org/10.1038/369556a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7515481">Takeshima et al. (1994)</a> developed mice with a targeted mutation in the Ryr1 gene. Homozygous mice died perinatally with gross abnormalities of skeletal muscle. The contractile response to electrical stimulation under physiologic conditions was totally abolished in mutant embryonic muscle. However, ryanodine receptors other than Ryr1 seemed to exist, because a response to caffeine was retained. <a href="#78" class="mim-tip-reference" title="Takeshima, H., Iino, M., Takekura, H., Nishi, M., Kuno, J., Minowa, O., Takano, H., Noda, T. <strong>Excitation-contraction uncoupling and muscular degeneration in mice lacking functional skeletal muscle ryanodine-receptor gene.</strong> Nature 369: 556-559, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7515481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7515481</a>] [<a href="https://doi.org/10.1038/369556a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7515481">Takeshima et al. (1994)</a> concluded that RYR1 is essential for both muscular maturation and excitation-contraction coupling and that RYR1 function during excitation-contraction coupling cannot be substituted by other receptor subtypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7515481" 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="#79" class="mim-tip-reference" title="Takeshima, H., Yamazawa, T., Ikemoto, T., Takekura, H., Nishi, M., Noda, T., Iino, M. <strong>Ca(2+)-induced Ca(2+) release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor.</strong> EMBO J. 14: 2999-3006, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7621815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7621815</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1995.tb07302.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7621815">Takeshima et al. (1995)</a> demonstrated that the residual caffeine-activated calcium release in Ryr1 null mice is likely mediated by Ryr3 (<a href="/entry/180903">180903</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7621815" 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="#4" class="mim-tip-reference" title="Barone, V., Bertocchini, F., Bottinelli, R., Protasi, F., Allen, P. D., Armstrong, C. F., Reggiani, C., Sorrentino, V. <strong>Contractile impairment and structural alterations of skeletal muscles from knockout mice lacking type 1 and type 3 ryanodine receptors.</strong> FEBS Lett. 422: 160-164, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489997</a>] [<a href="https://doi.org/10.1016/s0014-5793(98)00003-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9489997">Barone et al. (1998)</a> generated double mutant mice carrying a targeted disruption of both the Ryr1 and the Ryr3 (<a href="/entry/180903">180903</a>) genes. Skeletal muscles from mice homozygous for both mutations did not contract in response to caffeine or ryanodine. In addition, these muscles showed very low tension when directly activated with micromolar ionized calcium after membrane permeabilization, indicating either poor development or degeneration of the myofibrils. This was confirmed by biochemical analysis of contractile proteins. Electron microscopy confirmed small size of myofibrils and showed complete absence of ryanodine receptors in the junctional sarcoplasmic reticulum. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9489997" 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="Chelu, M. G., Goonasekera, S. A., Durham, W. J., Tang, W., Lueck, J. D., Riehl, J., Pessah, I. N., Zhang, P., Bhattacharjee, M. B., Dirksen, R. T., Hamilton, S. L. <strong>Heat- and anesthesia-induced malignant hyperthermia in an RyR1 knock-in mouse.</strong> FASEB J. 20: 329-330, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16284304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16284304</a>] [<a href="https://doi.org/10.1096/fj.05-4497fje" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16284304">Chelu et al. (2006)</a> found that mice with a homozygous for the Y522S (<a href="#0031">180901.0031</a>) mutation in the Ryr1 gene exhibited skeletal defects and died during embryonic development or soon after birth. Heterozygous mice, corresponding to the human occurrence of this mutation, were susceptible to malignant hyperthermia and showed whole body contractions and elevated core temperatures in response to isoflurane exposure or heat stress. Skeletal muscles from heterozygous mice exhibit increased susceptibility to caffeine- and heat-induced contractures in vitro. In addition, the heterozygous expression of the mutation resulted in enhanced RyR1 sensitivity to activation by temperature, caffeine, and voltage but not uncompensated sarcoplasmic reticulum calcium leak or store depletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16284304" 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="Durham, W. J., Aracena-Parks, P., Long, C., Rossi, A. E., Goonasekera, S. A., Boncompagni, S., Galvan, D. L., Gilman, C. P., Baker, M. R., Shirokova, N., Protasi, F., Dirksen, R., Hamilton, S. L. <strong>RyR1 S-nitrosylation underlies environmental heat stroke and sudden death in Y522S RyR1 knockin mice.</strong> Cell 133: 53-65, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18394989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18394989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18394989[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/10.1016/j.cell.2008.02.042" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18394989">Durham et al. (2008)</a> found that skeletal muscle from heterozygous Y522S-mutant mice displayed increased basal oxidative stress with increased levels of reactive oxygen and nitrogen species compared to wildtype mice. Further studies suggested that the reactive species resulted from increased calcium release from the leaky mutant RyR1 channel in resting muscles. Increased calcium combined with increased reactive nitrogen species produced S-nitrosylation of the mutant leaky channel that further enhanced channel activity at increased temperatures. <a href="#17" class="mim-tip-reference" title="Durham, W. J., Aracena-Parks, P., Long, C., Rossi, A. E., Goonasekera, S. A., Boncompagni, S., Galvan, D. L., Gilman, C. P., Baker, M. R., Shirokova, N., Protasi, F., Dirksen, R., Hamilton, S. L. <strong>RyR1 S-nitrosylation underlies environmental heat stroke and sudden death in Y522S RyR1 knockin mice.</strong> Cell 133: 53-65, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18394989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18394989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18394989[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/10.1016/j.cell.2008.02.042" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18394989">Durham et al. (2008)</a> postulated a destructive feed-forward cycle of increased calcium release, increased temperature-sensitivity of the mutant channel, and increased muscle contraction with elevated temperature and heat stress. Over time, this cycle induced a myopathy characterized by damaged mitochondria and decreased force generation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18394989" 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="Bellinger, A. M., Reiken, S., Carlson, C., Mongillo, M., Liu, X., Rothman, L., Matecki, S., Lacampagne, A., Marks, A. R. <strong>Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle.</strong> Nature Med. 15: 325-330, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19198614/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19198614</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19198614[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/10.1038/nm.1916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19198614">Bellinger et al. (2009)</a> found that the Ryr1 channel in skeletal muscle from the mdx mouse, a model of Duchenne muscular dystrophy (DMD; <a href="/entry/310200">310200</a>) with disruption of the dystrophin gene (DMD; <a href="/entry/300377">300377</a>), showed increased inducible nitric oxide (NOS2A; <a href="/entry/163730">163730</a>)-mediated S-nitrosylation of cysteine residues, which depleted the channel complex of calstabin-1 (FKBP12; <a href="/entry/186945">186945</a>). This resulted in leaky channels with increased calcium flux. These changes were age-dependent and coincided with dystrophic changes in muscle. Prevention of calstabin-1 depletion from Ryr1 with S107, a compound that binds the Ryr1 channel and enhances binding affinity, inhibited sarcoplasmic reticulum calcium leak, reduced biochemical and histologic evidence of muscle damage, improved muscle function, and increased exercise performance in mdx mice. <a href="#5" class="mim-tip-reference" title="Bellinger, A. M., Reiken, S., Carlson, C., Mongillo, M., Liu, X., Rothman, L., Matecki, S., Lacampagne, A., Marks, A. R. <strong>Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle.</strong> Nature Med. 15: 325-330, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19198614/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19198614</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19198614[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/10.1038/nm.1916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19198614">Bellinger et al. (2009)</a> proposed that the increased calcium flux via a defective Ryr1 channel contributes to muscle weakness and degeneration in DMD by increasing calcium-activated proteases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19198614" 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>To understand the skeletal muscle pathology in patients with an RYR1 mutation that results in decreased RYR1 protein content (e.g., Q1979X), <a href="#20" class="mim-tip-reference" title="Elbaz, M., Ruiz, A., Eckhardt, J., Pelczar, O., Muntoni, F. Boncompagni, S., Treves, S., Zorzato, F. <strong>Quantitative reduction of RyR1 protein caused by a single-allele frameshift mutation in RYR1 ex36 impairs the strength of adult skeletal muscle fibres.</strong> Hum. Molec. Genet. 28: 1872-1884, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30689883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30689883</a>] [<a href="https://doi.org/10.1093/hmg/ddz025" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30689883">Elbaz et al. (2019)</a> generated a mouse model with a heterozygous mutation in exon 36 (Gln1970fsTer16) of the Ryr1 gene. Mice heterozygous for the mutation had lower running distance before and after exercise training, and lower median cruise speed, compared to wildtype littermates. Ryr1 protein content was lower in mutant mice compared to wildtype in the extensor digitorum longus (EDL) (37.6% of wildtype) and soleus muscles (58.7% of wildtype), and gene transcript levels were 50% of wildtype levels. Electron microscopy studies in EDL muscles from mutant mice showed an uneven distribution and abnormal morphology of calcium release units (CRUs), including an increase of CRUs with only 2 elements, suggesting a reduction in the number of calcium release sites. Functional studies showed that muscle strength and depolarization-induced calcium transients were reduced in mutant mice, at 20% and 15% of wildtype, respectively. Because the level of Ryr1 protein content was quantitatively more abnormal than strength and peak calcium transient deficiencies in the mutant mice, <a href="#20" class="mim-tip-reference" title="Elbaz, M., Ruiz, A., Eckhardt, J., Pelczar, O., Muntoni, F. Boncompagni, S., Treves, S., Zorzato, F. <strong>Quantitative reduction of RyR1 protein caused by a single-allele frameshift mutation in RYR1 ex36 impairs the strength of adult skeletal muscle fibres.</strong> Hum. Molec. Genet. 28: 1872-1884, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30689883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30689883</a>] [<a href="https://doi.org/10.1093/hmg/ddz025" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30689883">Elbaz et al. (2019)</a> suggested that there may be an adaptation to chronic Ryr1 protein deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30689883" 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="Elbaz, M., Ruiz, A., Bachmann, C., Eckhardt, J., Pelczar, P., Venturi, E., Lindsay, C., Wilson, A. D., Alhussni, A., Humberstone, T., Pietrangelo, L., Boncompagni, S., Sitsapesan, R., Treves, S., Zorzato, F. <strong>Quantitative RyR1 reduction and loss of calcium sensitivity of RyR1Q1970fsX16+A4329D cause cores and loss of muscle strength.</strong> Hum. Molec. Genet. 28: 2987-2999, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31044239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31044239</a>] [<a href="https://doi.org/10.1093/hmg/ddz092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31044239">Elbaz et al. (2019)</a> generated a mouse model with compound heterozygous mutations in RYR1, Q1970fsX16 in exon 36 and A4329D in exon 91, which are isogenic to the RYR1 mutations identified in a severely affected child with autosomal recessive multiminicore disease (see <a href="/entry/255320">255320</a>). Both Ryr1 protein and transcript levels were reduced in muscle from the mutant mice, and Hdac4 protein (<a href="/entry/605314">605314</a>) was found to be upregulated. Compared to their wildtype littermates, mutant mice had lower body weight at age 18 weeks, and lower spontaneous running distance and cruising speed at age 3 months. Histologic examination of mutant muscles showed regions of severe myofibrillar disorganization as well as reduced numbers of calcium release units (CRUs) and mitochondria. Functional testing showed that the mutant muscles developed less isometric force and had smaller evoked calcium transients. <a href="#19" class="mim-tip-reference" title="Elbaz, M., Ruiz, A., Bachmann, C., Eckhardt, J., Pelczar, P., Venturi, E., Lindsay, C., Wilson, A. D., Alhussni, A., Humberstone, T., Pietrangelo, L., Boncompagni, S., Sitsapesan, R., Treves, S., Zorzato, F. <strong>Quantitative RyR1 reduction and loss of calcium sensitivity of RyR1Q1970fsX16+A4329D cause cores and loss of muscle strength.</strong> Hum. Molec. Genet. 28: 2987-2999, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31044239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31044239</a>] [<a href="https://doi.org/10.1093/hmg/ddz092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31044239">Elbaz et al. (2019)</a> concluded that the mutant mice recapitulated the clinical features seen in patients with multiminicore disease and provided insight into the pathologic mechanism of the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31044239" 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="#8" class="mim-tip-reference" title="Brennan, S., Garcia-Castaneda, M., Michelucci, A., Sabha, N., Malik, S., Groom, L., LaPierre, L. W., Dowling, J. J., Dirksen, R. T. <strong>Mouse model of severe recessive RYR1-related myopathy.</strong> Hum. Molec. Genet. 28: 3024-3036, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31107960/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31107960</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31107960[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/ddz105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31107960">Brennan et al. (2019)</a> generated a compound heterozygous mouse model of RYR1-related myopathy (RYR1-RM) in which one allele of Ryr1 had a thr4709-to-met (T4709M) mutation, equivalent to human T4706M, and the other allele had a 16-bp frameshift deletion in exon 96. Mutant mice were born at the expected mendelian frequency, although a small number died during the first 3 days of life. Mutant mice that survived beyond 3 days exhibited reduced body weight due to a substantial reduction of the myofiber compartment. The disease progressed rapidly, with most mice dying before 57 days of age due to respiratory failure caused by spine changes and muscle weakness. Mutant mice exhibited reduced muscle force generation, and mutant muscles had decreased myofiber size but preserved muscle structure. Levels of Ryr1 and Dhpr (QDPR; <a href="/entry/612676">612676</a>) proteins were reduced in mutant muscles, and combined with reduced muscle force generation, this reduction led to aberrant intracellular calcium dynamics in mutant mice. Knockin mice homozygous for the T4709M mutation displayed a potentially lethal hyperthermic response during isoflurane exposure, recapitulating the enhanced sensitivity to volatile anesthetics seen in RYR1-RM patients with malignant hyperthermia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31107960" 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>45 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/180901" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=180901[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 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, ARG614CYS
|
|
</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> rs118192172 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192172;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/rs118192172?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=rs118192172" 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=rs118192172" 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=RCV000013830 OR RCV000119586 OR RCV000538121 OR RCV000608635 OR RCV000624176 OR RCV001787388 OR RCV001787389 OR RCV001787390 OR RCV001787391 OR RCV001787392 OR RCV001787393 OR RCV001787394 OR RCV002496349" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013830, RCV000119586, RCV000538121, RCV000608635, RCV000624176, RCV001787388, RCV001787389, RCV001787390, RCV001787391, RCV001787392, RCV001787393, RCV001787394, RCV002496349" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013830...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 members of 1 of 35 Canadian families with malignant hyperthermia (MHS1; <a href="/entry/145600">145600</a>), <a href="#31" class="mim-tip-reference" title="Gillard, E. F., Otsu, K., Fujii, J., Khanna, V. K., de Leon, S., Derdemezi, J., Britt, B. A., Duff, C. L., Worton, R. G., MacLennan, D. H. <strong>A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia.</strong> Genomics 11: 751-755, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1774074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1774074</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90084-r" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1774074">Gillard et al. (1991)</a> identified a heterozygous c.1840C-T transition in the RYR1 gene, resulting in an arg614-to-cys (R614C) substitution, which is comparable to the R615C mutation found in pigs with malignant hyperthermia (see ANIMAL MODEL). Of the mutation carriers, the proband experienced an episode of malignant hyperthermia during surgery, and the other 2 (her mother and sister) had positive muscle biopsy contracture tests. The proband's father and brother, who did not carry the mutation, had negative contracture tests. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1774074" 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="#34" class="mim-tip-reference" title="Hall-Curran, J. L., Stewart, A. D., Ball, S. P., Halsall, J. P., Hopkins, P. M., Ellis, F. R. <strong>No C1840 to T mutation in RYR1 in malignant hyperthermia. (Letter)</strong> Hum. Mutat. 2: 330, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8401544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8401544</a>] [<a href="https://doi.org/10.1002/humu.1380020418" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8401544">Hall-Curran et al. (1993)</a> did not identify the R614C mutation in in 100 British families with malignant hyperthermia, suggesting that the prevalence of this mutation is less than 3% in the U.K. population. The authors concluded that presymptomatic testing for R614C, as suggested by <a href="#63" class="mim-tip-reference" title="Otsu, K., Phillips, M. S., Khanna, V. K., de Leon, S., MacLennan, D. H. <strong>Refinement of diagnostic assays for a probable causal mutation for porcine and human malignant hyperthermia.</strong> Genomics 13: 835-837, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1639409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1639409</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90163-m" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1639409">Otsu et al. (1992)</a>, would have no practicality in the British population. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8401544+1639409" 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 a German family with MHS, <a href="#14" class="mim-tip-reference" title="Deufel, T., Sudbrak, R., Feist, Y., Rubsam, B., Du Chesne, I., Schafer, K.-L., Roewer, N., Grimm, T., Lehmann-Horn, F., Hartung, E. J., Muller, C. R. <strong>Discordance, in a malignant hyperthermia pedigree, between in vitro contracture-test phenotypes and haplotypes for the MHS1 region on chromosome 19q12-13.2, comprising the C1840T transition in the RYR1 gene.</strong> Am. J. Hum. Genet. 56: 1334-1342, 1995. Note: Erratum: Am. J. Hum. Genet. 57: 520 only, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7762556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7762556</a>]" pmid="7762556">Deufel et al. (1995)</a> identified the R614C mutation in homozygosity or heterozygosity in affected individuals. In vitro contracture test (IVCT) phenotypes were similar between heterozygotes and 1 homozygous individual (408). The mutation was present on 2 different haplotypes in the family. In addition, 3 individuals with MHS in a different branch of the family did not carry the R614C mutation; IVCT results for these affected individuals did not differ from those carrying the R614C mutation. The authors suggested that the results may challenge the causative role of the mutation and possibly the role of the RYR1 gene itself in human malignant hyperthermia susceptibility, at least in some cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7762556" 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>Fagerlund et al. (<a href="#26" class="mim-tip-reference" title="Fagerlund, T., Ording, H., Bendixen, D., Berg, K. <strong>Search for three known mutations in the RYR gene in 48 Danish families with malignant hyperthermia.</strong> Clin. Genet. 46: 401-404, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7889656/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7889656</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1994.tb04406.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7889656">1994</a>, <a href="#23" class="mim-tip-reference" title="Fagerlund, T. H., Islander, G., Twetman, E. R., Berg, K. <strong>A search for three known RYR1 gene mutations in 41 Swedish families with predisposition to malignant hyperthermia.</strong> Clin. Genet. 48: 12-16, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7586638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7586638</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1995.tb04047.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7586638">1995</a>) found the R614C mutation in 3 of 41 Swedish families with MHS, but in none of 48 Danish families. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7889656+7586638" 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="Fagerlund, T. H., Ording, H., Bendixen, D., Islander, G., Ranklev Twetman, E., Berg, K. <strong>Discordance between malignant hyperthermia susceptibility and RYR1 mutation C1840T in two Scandinavian MH families exhibiting this mutation.</strong> Clin. Genet. 52: 416-421, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9520251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9520251</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1997.tb02561.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9520251">Fagerlund et al. (1997)</a> reported 2 families in which there was recombination between MH susceptibility and the R614C mutation, in 1 and 3 individuals, respectively. They suggested that these findings make it necessary to reconsider the specificity of the in vitro contracture test (IVCT) and/or the role of R614C as a cause of MH susceptibility in some families exhibiting this mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9520251" 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>Variant Function</em></strong></p><p>
|
|
<a href="#62" class="mim-tip-reference" title="Otsu, K., Nishida, K., Kimura, Y., Kuzuya, T., Hori, M., Kamada, T., Tada, M. <strong>The point mutation arg615-to-cys in the Ca(2+) release channel of skeletal sarcoplasmic reticulum is responsible for hypersensitivity to caffeine and halothane in malignant hyperthermia.</strong> J. Biol. Chem. 269: 9413-9415, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7511586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7511586</a>]" pmid="7511586">Otsu et al. (1994)</a> designed experiments to demonstrate physiologically that the R614C mutation alters ryanodine receptor function. They estimated cytoplasmic calcium ion responses to halothane and caffeine in myoblastic cells expressing the normal or mutant ryanodine receptor by transfecting the corresponding cDNAs. Exposure to clinical doses of halothane resulted in a rapid increase in calcium ion in cells expressing the mutant receptor, whereas no calcium changes were observed in cells expressing the wildtype receptor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7511586" 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 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, GLY248ARG
|
|
</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> rs1801086 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1801086;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/rs1801086?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=rs1801086" 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=rs1801086" 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=RCV000013831 OR RCV000119713 OR RCV001851834 OR RCV004017237" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013831, RCV000119713, RCV001851834, RCV004017237" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013831...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs (TJ and SJ, family 39) with malignant hyperthermia (MHS1; <a href="/entry/145600">145600</a>), <a href="#30" class="mim-tip-reference" title="Gillard, E. F., Otsu, K., Fujii, J., Duff, C., de Leon, S., Khanna, V. K., Britt, B. A., Worton, R. G., MacLennan, D. H. <strong>Polymorphisms and deduced amino acid substitutions in the coding sequence of the ryanodine receptor (RYR1) gene in individuals with malignant hyperthermia.</strong> Genomics 13: 1247-1254, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1354642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1354642</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90042-q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1354642">Gillard et al. (1992)</a> identified a heterozygous G-to-A transition in the RYR1 gene that resulted in a gly248-to-arg (G248R) substitution. The mutation was identified by PCR amplification followed by direct sequencing. The proband, TJ, experienced an episode of malignant hyperthermia while undergoing tonsillectomy, and also had muscle cramps. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1354642" 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 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT, WITH SUSCEPTIBILITY TO MALIGNANT HYPERTHERMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, ARG2435HIS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28933396 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933396;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=rs28933396" 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=rs28933396" 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=RCV000013832 OR RCV000119699 OR RCV000707405 OR RCV001787395 OR RCV001787396 OR RCV001787397 OR RCV001787398 OR RCV001787399 OR RCV001787400 OR RCV001787401 OR RCV002281705 OR RCV004017238" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013832, RCV000119699, RCV000707405, RCV001787395, RCV001787396, RCV001787397, RCV001787398, RCV001787399, RCV001787400, RCV001787401, RCV002281705, RCV004017238" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013832...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a large Canadian family with congenital myopathy-1A (CMYO1A; <a href="/entry/117000">117000</a>) manifest as central core disease on skeletal muscle biopsy, <a href="#92" class="mim-tip-reference" title="Zhang, Y., Chen, H. S., Khanna, V. K., De Leon, S., Phillips, M. S., Schappert, K., Britt, B. A., Brownell, A. K. W., MacLennan, D. H. <strong>A mutation in the human ryanodine receptor gene associated with central core disease.</strong> Nature Genet. 5: 46-50, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8220422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8220422</a>] [<a href="https://doi.org/10.1038/ng0993-46" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8220422">Zhang et al. (1993)</a> identified a heterozygous c.7301G-A transition in the RYR1 gene, resulting in an arg2434-to-his (ARG2434HIS) substitution. This appeared to be a 'private' mutation since it was restricted to this single large family among more than 100 Canadian CCD and MHS families tested. Some members of the family had previously been reported by <a href="#75" class="mim-tip-reference" title="Shuaib, A., Paasuke, R. T., Brownell, K. W. <strong>Central core disease: clinical features in 13 patients.</strong> Medicine 66: 389-396, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3626847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3626847</a>]" pmid="3626847">Shuaib et al. (1987)</a> as having mild myopathy, central cores on muscle biopsy, and susceptibility to malignant hyperthermia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3626847+8220422" 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="#69" class="mim-tip-reference" title="Richter, M., Schleithoff, L., Deufel, T., Lehmann-Horn, F., Herrmann-Frank, A. <strong>Functional characterization of a distinct ryanodine receptor mutation in human malignant hyperthermia-susceptible muscle.</strong> J. Biol. Chem. 272: 5256-5260, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9030597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9030597</a>] [<a href="https://doi.org/10.1074/jbc.272.8.5256" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9030597">Richter et al. (1997)</a> referred to this mutation as arg2435-to- his (R2435H), according to the revised numbering of amino acids based on the corrected sequence data of <a href="#64" class="mim-tip-reference" title="Phillips, M. S., Fujii, J., Khanna, V. K., DeLeon, S., Yokobata, K., De Jong, P. J., MacLennan, D. H. <strong>The structural organization of the human skeletal muscle ryanodine receptor (RYR1) gene.</strong> Genomics 34: 24-41, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8661021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8661021</a>] [<a href="https://doi.org/10.1006/geno.1996.0238" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8661021">Phillips et al. (1996)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9030597+8661021" 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 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT, WITH SUSCEPTIBILITY TO MALIGNANT HYPERTHERMIA, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, ARG163CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118192161 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192161;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=rs118192161" 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=rs118192161" 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=RCV000013833 OR RCV000013834 OR RCV000119625 OR RCV000806352 OR RCV001787402 OR RCV001787706 OR RCV001787707 OR RCV001787708 OR RCV001787709 OR RCV001787710 OR RCV001787711 OR RCV004017239" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013833, RCV000013834, RCV000119625, RCV000806352, RCV001787402, RCV001787706, RCV001787707, RCV001787708, RCV001787709, RCV001787710, RCV001787711, RCV004017239" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013833...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 2 unrelated families (2T and D15) with susceptibility to malignant hyperthermia (MHS1; <a href="/entry/145600">145600</a>), <a href="#65" class="mim-tip-reference" title="Quane, K. A., Healy, J. M. S., Keating, K. E., Manning, B. M., Couch, F. J., Palmucci, L. M., Doriguzzi, C., Fagerlund, T. H., Berg, K., Ording, H., Bendixen, D., Mortier, W., Linz, U., Muller, C. R., McCarthy, T. V. <strong>Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia.</strong> Nature Genet. 5: 51-55, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8220423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8220423</a>] [<a href="https://doi.org/10.1038/ng0993-51" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8220423">Quane et al. (1993)</a> identified heterozygosity for a c.487C-T transition in the RYR1 gene that resulted in an arg163-to-cys (R163C) substitution. In family 2T, some persons also had manifestations of a congenital myopathy (CMYO1A; <a href="/entry/117000">117000</a>) with central cores on skeletal muscle biopsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8220423" 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="#60" class="mim-tip-reference" title="O'Brien, R. O., Taske, N. L., Hansbro, P. M., Matthaei, K. I., Hogan, S. P., Denborough, M. A., Foster, P. S. <strong>Exclusion of defects in the skeletal muscle specific regions of the DHPR alpha-1 subunit as frequent causes of malignant hyperthermia.</strong> J. Med. Genet. 32: 913-914, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8592342/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8592342</a>] [<a href="https://doi.org/10.1136/jmg.32.11.913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8592342">O'Brien et al. (1995)</a> reported a family in which 2 members diagnosed with MHS by means of the in vitro contracture test were found to be heterozygous for the R163C mutation, but 2 other members diagnosed with MHS on the same basis did not have the mutation. Reference was made to other families in which the major phenotype did not cosegregate with the arg614-to-cys (R614C; <a href="#0001">180901.0001</a>) or the gly341-to-arg (G341R; <a href="#0006">180901.0006</a>) mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8592342" 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>Fagerlund et al. (<a href="#26" class="mim-tip-reference" title="Fagerlund, T., Ording, H., Bendixen, D., Berg, K. <strong>Search for three known mutations in the RYR gene in 48 Danish families with malignant hyperthermia.</strong> Clin. Genet. 46: 401-404, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7889656/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7889656</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1994.tb04406.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7889656">1994</a>, <a href="#23" class="mim-tip-reference" title="Fagerlund, T. H., Islander, G., Twetman, E. R., Berg, K. <strong>A search for three known RYR1 gene mutations in 41 Swedish families with predisposition to malignant hyperthermia.</strong> Clin. Genet. 48: 12-16, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7586638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7586638</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1995.tb04047.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7586638">1995</a>) found the heterozygous R163C mutation in 1 of 48 Danish families with MHS, but in none of 41 Swedish families. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7889656+7586638" 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="#82" class="mim-tip-reference" title="Tobin, J. R., Jason, D. R., Challa, V. R., Nelson, T. E., Sambuughin, N. <strong>Malignant hyperthermia and apparent heat stroke. (Letter)</strong> JAMA 286: 168-169, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11448278/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11448278</a>] [<a href="https://doi.org/10.1001/jama.286.2.168" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11448278">Tobin et al. (2001)</a> identified a heterozygous R163C mutation in a 12-year-old boy with MHS. The patient's father also carried the mutation. The boy experienced an episode of MH during surgery for reduction of a humerus fracture, from which he recovered; he died 8 months later after participation in a football game when the ambient temperature was approximately 80 degrees F, with apparent heat stroke (rectal temperature greater than 108 degrees F). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11448278" 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 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, ILE403MET
|
|
</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> rs118192116 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192116;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/rs118192116?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=rs118192116" 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=rs118192116" 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=RCV000013835 OR RCV000119453 OR RCV001787712 OR RCV001787713 OR RCV001787714 OR RCV001787715 OR RCV001787716 OR RCV001787717 OR RCV001787718 OR RCV003231102 OR RCV003591629 OR RCV004782014" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013835, RCV000119453, RCV001787712, RCV001787713, RCV001787714, RCV001787715, RCV001787716, RCV001787717, RCV001787718, RCV003231102, RCV003591629, RCV004782014" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013835...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 affected brothers from an Italian family (4T) with congenital myopathy-1A (CMYO1A; <a href="/entry/117000">117000</a>) and central cores on skeletal muscle biopsy, <a href="#65" class="mim-tip-reference" title="Quane, K. A., Healy, J. M. S., Keating, K. E., Manning, B. M., Couch, F. J., Palmucci, L. M., Doriguzzi, C., Fagerlund, T. H., Berg, K., Ording, H., Bendixen, D., Mortier, W., Linz, U., Muller, C. R., McCarthy, T. V. <strong>Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia.</strong> Nature Genet. 5: 51-55, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8220423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8220423</a>] [<a href="https://doi.org/10.1038/ng0993-51" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8220423">Quane et al. (1993)</a> demonstrated heterozygosity for a c.1209C-G transversion in the RYR1 gene that resulted in an ile403-to-met substitution (I403M). The sibs inherited the mutation from their clinically normal father, who was not available for biopsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8220423" 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 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, GLY341ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121918592 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918592;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=rs121918592" 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=rs121918592" 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=RCV000013836 OR RCV000119406 OR RCV000655541" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013836, RCV000119406, RCV000655541" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013836...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected individuals from 3 unrelated families with malignant hyperthermia susceptibility (MHS1; <a href="/entry/145600">145600</a>), <a href="#67" class="mim-tip-reference" title="Quane, K. A., Keating, K. E., Manning, B. M., Healy, J. M. S., Monsieurs, K., Heffron, J. J. A., Lehane, M., Heytens, L., Krivosic-Horber, R., Adnet, P., Ellis, F. R., Monnier, N., Lunardi, J., McCarthy, T. V. <strong>Detection of a novel common mutation in the ryanodine receptor gene in malignant hyperthermia: implications for diagnosis and heterogeneity studies.</strong> Hum. Molec. Genet. 3: 471-476, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8012359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8012359</a>] [<a href="https://doi.org/10.1093/hmg/3.3.471" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8012359">Quane et al. (1994)</a> identified a heterozygous c.1021G-A transition in the RYR1 gene, resulting in a gly341-to-arg (G341R) substitution. The authors suggested that the G341R mutation may be responsible for approximately 10% of all MHS cases in Caucasians. However, <a href="#27" class="mim-tip-reference" title="Fagerlund, T., Ording, H., Bendixen, D., Islander, G., Ranklev-Twetman, E., Berg, K. <strong>RYR1 mutation G1021A (gly341-to-arg) is not frequent in Danish and Swedish families with malignant hyperthermia susceptibility.</strong> Clin. Genet. 49: 186-188, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8828983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8828983</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1996.tb03284.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8828983">Fagerlund et al. (1996)</a> discovered this mutation in only 1 of 89 Swedish and Danish families with MHS. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8828983+8012359" 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="#2" class="mim-tip-reference" title="Alestrom, A., Fagerlund, T. H., Berg, K. <strong>A simple method to detect the RYR1 mutation G1021A, a cause of malignant hyperthermia susceptibility.</strong> Clin. Genet. 47: 274-275, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7554356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7554356</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1995.tb04311.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7554356">Alestrom et al. (1995)</a> used the amplification-created restriction sites (ACRS) technique to detect the G341R mutation. The method discriminated quickly and efficiently between homozygotes with the mutation, heterozygotes, and homozygotes without the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7554356" 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="Adeokun, A. M., West, S. P., Ellis, F. R., Halsall, P. J., Hopkins, P. M., Foroughmand, A. M., Iles, D. E., Robinson, R. L., Stewart, A. D., Curran, J. L. <strong>The G1021A substitution in the RYR1 gene does not cosegregate with malignant hyperthermia susceptibility in a British pedigree.</strong> Am. J. Hum. Genet. 60: 833-341, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9106529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9106529</a>]" pmid="9106529">Adeokun et al. (1997)</a> reported a large family in which the G341R mutation did not show complete cosegregation with MHS: it occurred in only 7 of 12 individuals in the kinship demonstrated to be MH sensitive by in vitro contracture tests (IVCTs), and susceptibility was inherited from parents who were homozygous wildtype c.1021G, as well as from parents who were heterozygotes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9106529" 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="#59" class="mim-tip-reference" title="Monsieurs, K. G., Van Broeckhoven, C., Martin, J.-J., Van Hoof, V. O., Heytens, L. <strong>Gly341arg mutation indicating malignant hyperthermia susceptibility: specific cause of chronically elevated serum creatine kinase activity.</strong> J. Neurol. Sci. 154: 62-65, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9543323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9543323</a>] [<a href="https://doi.org/10.1016/s0022-510x(97)00215-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9543323">Monsieurs et al. (1998)</a> found that 9 of 13 carriers of the G341R mutation in 2 families had elevated serum creatine kinase levels (up to 6 times the upper limit of normal). All had normal neurologic exams and muscle histology. The third family did not show increased creatine kinase levels. The authors suggested that the G341R mutation may be a cause of chronic elevation of serum creatine kinase in asymptomatic individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9543323" 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>Whereas the G341R mutation is a frequent cause of malignant hyperthermia in European populations, <a href="#76" class="mim-tip-reference" title="Stewart, S. L., Rosenberg, H., Fletcher, J. E. <strong>Failure to identify the ryanodine receptor G1021A mutation in a large North American population with malignant hyperthermia.</strong> Clin. Genet. 54: 358-361, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9831351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9831351</a>] [<a href="https://doi.org/10.1034/j.1399-0004.1998.5440417.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9831351">Stewart et al. (1998)</a> did not find the mutation in 114 North American individuals screened because of a family history or personal history of malignant hyperthermia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9831351" 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 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, GLY2434ARG
|
|
</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> rs121918593 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918593;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/rs121918593?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=rs121918593" 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=rs121918593" 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=RCV000013837 OR RCV000119698 OR RCV000551243 OR RCV000612258 OR RCV001787719 OR RCV001787720 OR RCV001787721 OR RCV001787722 OR RCV001787723 OR RCV001787724 OR RCV001787725 OR RCV002288488 OR RCV002513026 OR RCV005025050" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013837, RCV000119698, RCV000551243, RCV000612258, RCV001787719, RCV001787720, RCV001787721, RCV001787722, RCV001787723, RCV001787724, RCV001787725, RCV002288488, RCV002513026, RCV005025050" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013837...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected individuals from 4 of 104 unrelated families with malignant hyperthermia susceptibility (MHS1; <a href="/entry/145600">145600</a>), <a href="#41" class="mim-tip-reference" title="Keating, K. E., Quane, K. A., Manning, B. M., Lehane, M., Hartung, E., Censier, K., Urwyler, A., Klausnitzer, M., Muller, C. R., Heffron, J. J. A., McCarthy, T. V. <strong>Detection of a novel RYR1 mutation in four malignant hyperthermia pedigrees.</strong> Hum. Molec. Genet. 3: 1855-1858, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7849712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7849712</a>] [<a href="https://doi.org/10.1093/hmg/3.10.1855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7849712">Keating et al. (1994)</a> identified a heterozygous gly2433-to-arg (GLY2433ARG) change in the RYR1 gene resulting from a c.7297G-A transition. The authors noted that this mutation is adjacent to the R2434H mutation (<a href="#0003">180901.0003</a>), which may indicate a second cluster in the RYR1 gene where MHS and/or central core disease (CMYO1A; <a href="/entry/117000">117000</a>) mutations occur. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7849712" 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 the numbering system of amino acids provided by the corrected sequence data for human RYR1 according to <a href="#64" class="mim-tip-reference" title="Phillips, M. S., Fujii, J., Khanna, V. K., DeLeon, S., Yokobata, K., De Jong, P. J., MacLennan, D. H. <strong>The structural organization of the human skeletal muscle ryanodine receptor (RYR1) gene.</strong> Genomics 34: 24-41, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8661021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8661021</a>] [<a href="https://doi.org/10.1006/geno.1996.0238" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8661021">Phillips et al. (1996)</a>, this mutation was referred to as G2434R by <a href="#69" class="mim-tip-reference" title="Richter, M., Schleithoff, L., Deufel, T., Lehmann-Horn, F., Herrmann-Frank, A. <strong>Functional characterization of a distinct ryanodine receptor mutation in human malignant hyperthermia-susceptible muscle.</strong> J. Biol. Chem. 272: 5256-5260, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9030597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9030597</a>] [<a href="https://doi.org/10.1074/jbc.272.8.5256" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9030597">Richter et al. (1997)</a>. Functional studies showed that the G2434R mutation enhanced the sensitivity of RYR1 to activating concentrations of calcium and to caffeine. In parallel, the sensitivity to inhibiting concentrations of calcium and calmodulin was reduced, transferring the mutant calcium-release channel into a hyperexcitable state. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9030597+8661021" 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 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, ARG2458CYS
|
|
</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> rs28933397 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933397;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/rs28933397?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=rs28933397" 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=rs28933397" 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=RCV000013838 OR RCV000119711 OR RCV000614410 OR RCV000796565 OR RCV001787726 OR RCV001787727 OR RCV001787728 OR RCV001787729 OR RCV001787730 OR RCV001787731 OR RCV001787732 OR RCV002490361" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013838, RCV000119711, RCV000614410, RCV000796565, RCV001787726, RCV001787727, RCV001787728, RCV001787729, RCV001787730, RCV001787731, RCV001787732, RCV002490361" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013838...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In families with malignant hyperthermia susceptibility (MHS1; <a href="/entry/145600">145600</a>), <a href="#49" class="mim-tip-reference" title="Manning, B. M., Quane, K. A., Lynch, P. J., Urwyler, A., Tegazzin, V., Krivosic-Horber, R., Censier, K., Comi, G., Adnet, P., Wolz, W., Lunardi, J., Muller, C. R., McCarthy, T. V. <strong>Novel mutations at a CpG dinucleotide in the ryanodine receptor in malignant hyperthermia.</strong> Hum. Mutat. 11: 45-50, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9450902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9450902</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:1<45::AID-HUMU7>3.0.CO;2-K" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9450902">Manning et al. (1998)</a> reported 2 novel mutations in the RYR1 gene: a heterozygous c.7372C-T transition, resulting in an arg2458-to-cys (R2458C) substitution, and a heterozygous c.7373G-A transition, resulting in an arg2458-to-his (R2458H; <a href="#0009">180901.0009</a>) substitution. Both changes occurred at a CpG dinucleotide in the central region of the RYR1 gene. The R2458C mutation was observed in a Swiss pedigree and in an Italian pedigree; the R2458H mutation was found in a French pedigree. Both mutations segregated with the malignant hyperthermia susceptibility phenotype or the MH equivocal (MHE) phenotype. The authors noted that these mutations represented the most C-terminal mutations in the RYR1 gene reported to that time. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9450902" 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 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, ARG2458HIS
|
|
</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> rs121918594 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918594;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/rs121918594?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=rs121918594" 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=rs121918594" 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=RCV000013839 OR RCV000079164 OR RCV000793289 OR RCV001787733 OR RCV001787734 OR RCV001787735 OR RCV001787736 OR RCV001787737 OR RCV001787738 OR RCV001787739 OR RCV004017240" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013839, RCV000079164, RCV000793289, RCV001787733, RCV001787734, RCV001787735, RCV001787736, RCV001787737, RCV001787738, RCV001787739, RCV004017240" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013839...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See <a href="#0008">180901.0008</a> and <a href="#49" class="mim-tip-reference" title="Manning, B. M., Quane, K. A., Lynch, P. J., Urwyler, A., Tegazzin, V., Krivosic-Horber, R., Censier, K., Comi, G., Adnet, P., Wolz, W., Lunardi, J., Muller, C. R., McCarthy, T. V. <strong>Novel mutations at a CpG dinucleotide in the ryanodine receptor in malignant hyperthermia.</strong> Hum. Mutat. 11: 45-50, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9450902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9450902</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:1<45::AID-HUMU7>3.0.CO;2-K" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9450902">Manning et al. (1998)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9450902" 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 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, ARG2163CYS
|
|
</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> rs118192175 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192175;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/rs118192175?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=rs118192175" 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=rs118192175" 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=RCV000013840 OR RCV000056223 OR RCV000119653 OR RCV001385701 OR RCV001787740 OR RCV001787741 OR RCV001787742 OR RCV001787743 OR RCV001787744 OR RCV001787745 OR RCV001787746" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013840, RCV000056223, RCV000119653, RCV001385701, RCV001787740, RCV001787741, RCV001787742, RCV001787743, RCV001787744, RCV001787745, RCV001787746" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013840...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated families (D1 and D2), <a href="#50" class="mim-tip-reference" title="Manning, B. M., Quane, K. A., Ording, H., Urwyler, A., Tegazzin, V., Lehane, M., O'Halloran, J., Hartung, E., Giblin, L. M., Lynch, P. J., Vaughan, P., Censier, K., Bendixen, D., Comi, G., Heytens, L., Monsieurs, K., Fagerlund, T., Wolz, W., Heffron, J. J. A., Muller, C. R., McCarthy, T. V. <strong>Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation.</strong> Am. J. Hum. Genet. 62: 599-609, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9497245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9497245</a>] [<a href="https://doi.org/10.1086/301748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9497245">Manning et al. (1998)</a> demonstrated that members with malignant hyperthermia (MHS1; <a href="/entry/145600">145600</a>) had a heterozygous c.6487C-T transition in the RYR1 gene, resulting in an arg2163-to-cys (R2163C) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9497245" 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 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, ARG2163HIS
|
|
</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> rs118192163 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192163;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/rs118192163?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=rs118192163" 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=rs118192163" 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=RCV000013841 OR RCV000013842 OR RCV000119654 OR RCV001204982 OR RCV001787747 OR RCV001787748 OR RCV001787749 OR RCV001787750 OR RCV001787751 OR RCV001787752 OR RCV001787753" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013841, RCV000013842, RCV000119654, RCV001204982, RCV001787747, RCV001787748, RCV001787749, RCV001787750, RCV001787751, RCV001787752, RCV001787753" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013841...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian mother and daughter (family It2) with MHS (<a href="/entry/145600">145600</a>), <a href="#50" class="mim-tip-reference" title="Manning, B. M., Quane, K. A., Ording, H., Urwyler, A., Tegazzin, V., Lehane, M., O'Halloran, J., Hartung, E., Giblin, L. M., Lynch, P. J., Vaughan, P., Censier, K., Bendixen, D., Comi, G., Heytens, L., Monsieurs, K., Fagerlund, T., Wolz, W., Heffron, J. J. A., Muller, C. R., McCarthy, T. V. <strong>Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation.</strong> Am. J. Hum. Genet. 62: 599-609, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9497245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9497245</a>] [<a href="https://doi.org/10.1086/301748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9497245">Manning et al. (1998)</a> identified a heterozygous c.6488G-A transition in the RYR1 gene, resulting in an arg2163-to-cys (R2163C) substitution. The family had been studied by <a href="#80" class="mim-tip-reference" title="Tegazzin, V., Accorsi, A., Gritti, G., Arcelli, L., Di Giovanni, A. <strong>MH fulminant reaction after eight anaesthetics: a case report.</strong> Minerva Anestesiol. 60: 217-219, 1994."None>Tegazzin et al. (1994)</a>. The proband had undergone 8 previous surgical procedures under general anesthesia before presenting with an MH crisis. On 6 of these previous occasions, an MH-triggering anesthetic had been used. Histologic examination of muscle biopsy from the mother revealed a predominance of type 1 fibers with central cores present in many fibers. Neither she nor her daughter had symptoms of a congenital myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9497245" 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="0012" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT, WITH SUSCEPTIBILITY TO MALIGNANT HYPERTHERMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, ILE4898THR
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118192170 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192170;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=rs118192170" 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=rs118192170" 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=RCV000013843 OR RCV000013844 OR RCV000119552 OR RCV000535754 OR RCV000763430 OR RCV001787754 OR RCV001787755 OR RCV001787756 OR RCV001787757 OR RCV001787758 OR RCV001787759 OR RCV001787760 OR RCV004586003 OR RCV004737150" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013843, RCV000013844, RCV000119552, RCV000535754, RCV000763430, RCV001787754, RCV001787755, RCV001787756, RCV001787757, RCV001787758, RCV001787759, RCV001787760, RCV004586003, RCV004737150" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013843...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a large Mexican kindred in which affected members through 4 generations had autosomal dominant congenital myopathy-1A (CMYO1A; <a href="/entry/117000">117000</a>) associated with central cores on muscle biopsy, <a href="#46" class="mim-tip-reference" title="Lynch, P. J., Tong, J., Lehane, M., Mallet, A., Giblin, L., Heffron, J. J. A., Vaughan, P., Zafra, G., MacLennan, D. H., McCarthy, T. V. <strong>A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca(2+) release channel function and severe central core disease.</strong> Proc. Nat. Acad. Sci. 96: 4164-4169, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10097181/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10097181</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10097181[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/10.1073/pnas.96.7.4164" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10097181">Lynch et al. (1999)</a> identified a heterozygous c.14693T-C transition in the RYR1 gene, resulting in an ile4898-to-thr (I4898T) mutation in the C-terminal transmembrane region of the RYR1 protein. In 2 family members tested, malignant hyperthermia was also present. <a href="#46" class="mim-tip-reference" title="Lynch, P. J., Tong, J., Lehane, M., Mallet, A., Giblin, L., Heffron, J. J. A., Vaughan, P., Zafra, G., MacLennan, D. H., McCarthy, T. V. <strong>A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca(2+) release channel function and severe central core disease.</strong> Proc. Nat. Acad. Sci. 96: 4164-4169, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10097181/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10097181</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10097181[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/10.1073/pnas.96.7.4164" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10097181">Lynch et al. (1999)</a> noted that all previously reported RYR1 mutations had been located either in the cytoplasmic N terminus or in a central cytoplasmic region of the protein. Introduction of the I4898T mutation into a rabbit RYR1 cDNA and expression in HEK293 cells resulted in abolition of response to the agonists halothane and caffeine. Coexpression of normal and mutant RYR1 cDNAs in a 1:1 ratio, however, produced RYR1 channels with normal halothane and caffeine sensitivities, but maximal levels of Ca(2+) release were reduced by 67%. Binding of [3H]ryanodine indicated that the heterozygous channel was activated by Ca(2+) concentrations 4-fold lower than normal. Single-cell analysis of cotransfected cells showed a significantly increased resting cytoplasmic Ca(2+) level and a significantly reduced luminal Ca(2+) level. These data indicated a leaky channel, possibly caused by a reduction in the Ca(2+) concentration required for channel activation. Comparison with 2 other coexpressed mutant/normal channels suggested that the I4898T mutation produces one of the most abnormal RYR1 channels that had been investigated, and this level of abnormality was reflected in the severe and penetrant phenotype of the patients with congenital myopathy in the pedigree. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10097181" 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="#81" class="mim-tip-reference" title="Tilgen, N., Zorzato, F., Halliger-Keller, B., Muntoni, F., Sewry, C., Palumucci, L. M., Schneider, C., Hauser, E., Lehmann-Horn, F., Muller, C. R., Treves, S. <strong>Identification of four novel mutations in the C-terminal membrane spanning domain of the ryanodine receptor 1: association with central core disease and alteration of calcium homeostasis.</strong> Hum. Molec. Genet. 10: 2879-2887, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741831</a>] [<a href="https://doi.org/10.1093/hmg/10.25.2879" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11741831">Tilgen et al. (2001)</a> identified the I4898T mutation, resulting from a c.14693T-C transition, in 3 of 25 unrelated individuals with CMYO1A. The isoleucine residue is highly conserved and is located in the C-terminal hydrophobic membrane-spanning region of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11741831" 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 2 members of a family (CCD05) and an unrelated patient (CCD11) with CMYO1A, <a href="#57" class="mim-tip-reference" title="Monnier, N., Romero, N. B., Lerale, J., Landrieu, P., Nivoche, Y., Fardeau, M., Lunardi, J. <strong>Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor.</strong> Hum. Molec. Genet. 10: 2581-2592, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709545</a>] [<a href="https://doi.org/10.1093/hmg/10.22.2581" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11709545">Monnier et al. (2001)</a> identified a heterozygous I4898T mutation in exon 102 of the RYR1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709545" 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>Variant Function</em></strong></p><p>
|
|
<a href="#3" class="mim-tip-reference" title="Avila, G., O'Brien, J. J., Dirksen, R. T. <strong>Excitation-contraction uncoupling by a human central core disease mutation in the ryanodine receptor.</strong> Proc. Nat. Acad. Sci. 98: 4215-4220, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11274444/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11274444</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11274444[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/10.1073/pnas.071048198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11274444">Avila et al. (2001)</a> expressed the analogous rabbit mutation (I4897T) in skeletal myotubes derived from Ryr1-knockout mice. They found that homozygous expression of I4897T in myotubes resulted in a complete uncoupling of sarcolemmal excitation from voltage-gated sarcoplasmic reticulum (SR) calcium ion release without significantly altering resting cytosolic calcium ion levels, sarcoplasmic reticulum calcium ion content, or Ryr1-mediated enhancement of dihydropyridine receptor (DHPR) channel activity. Coexpression of both I4897T and wildtype Ryr1 resulted in a 60% reduction in voltage-gated SR calcium ion release, again without altering resting cytosolic calcium ion levels, SR calcium ion content, or DHPR channel activity. These findings indicated that muscle weakness in patients with the I4898T mutation involves a functional uncoupling of sarcolemmal excitation from SR calcium ion release, rather than the expression of overactive or leaky SR calcium ion release channels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11274444" 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="0013" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, VAL2168MET
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118192176 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192176;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=rs118192176" 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=rs118192176" 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=RCV000013845 OR RCV000119656 OR RCV000557804 OR RCV000578323 OR RCV001729347 OR RCV001787761 OR RCV001787762 OR RCV001787763 OR RCV001787764 OR RCV001787765 OR RCV001787766 OR RCV001787767 OR RCV003398498" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013845, RCV000119656, RCV000557804, RCV000578323, RCV001729347, RCV001787761, RCV001787762, RCV001787763, RCV001787764, RCV001787765, RCV001787766, RCV001787767, RCV003398498" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013845...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected individuals from 8 Swiss families with malignant hyperthermia (MHS1; <a href="/entry/145600">145600</a>), <a href="#50" class="mim-tip-reference" title="Manning, B. M., Quane, K. A., Ording, H., Urwyler, A., Tegazzin, V., Lehane, M., O'Halloran, J., Hartung, E., Giblin, L. M., Lynch, P. J., Vaughan, P., Censier, K., Bendixen, D., Comi, G., Heytens, L., Monsieurs, K., Fagerlund, T., Wolz, W., Heffron, J. J. A., Muller, C. R., McCarthy, T. V. <strong>Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation.</strong> Am. J. Hum. Genet. 62: 599-609, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9497245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9497245</a>] [<a href="https://doi.org/10.1086/301748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9497245">Manning et al. (1998)</a> identified a heterozygous G-to-A change in the RYR1 gene, resulting in a val2168-to-met (V2168M) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9497245" 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="#57" class="mim-tip-reference" title="Monnier, N., Romero, N. B., Lerale, J., Landrieu, P., Nivoche, Y., Fardeau, M., Lunardi, J. <strong>Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor.</strong> Hum. Molec. Genet. 10: 2581-2592, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709545</a>] [<a href="https://doi.org/10.1093/hmg/10.22.2581" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11709545">Monnier et al. (2001)</a> identified a heterozygous V2168M mutation resulting from a c.6502G-A transition in exon 39 of the RYR1 gene in a 52-year-old patient (CCD14) with congenital myopathy-1A (CMYO1A; <a href="/entry/117000">117000</a>). She had a history of mild orthopedic problems during infancy, mild proximal muscle weakness, and cores on muscle biopsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709545" 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="0014" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
KING-DENBOROUGH SYNDROME, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, THR2206MET
|
|
</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> rs118192177 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192177;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/rs118192177?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=rs118192177" 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=rs118192177" 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=RCV000013846 OR RCV000119662 OR RCV000162149 OR RCV000606881 OR RCV000655558 OR RCV001729348 OR RCV004556715 OR RCV004658961 OR RCV005016260" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013846, RCV000119662, RCV000162149, RCV000606881, RCV000655558, RCV001729348, RCV004556715, RCV004658961, RCV005016260" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013846...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Malignant Hyperthermia, Susceptibility to, 1</em></strong></p><p>
|
|
In affected members of a family with malignant hyperthermia (MHS1; <a href="/entry/145600">145600</a>), <a href="#50" class="mim-tip-reference" title="Manning, B. M., Quane, K. A., Ording, H., Urwyler, A., Tegazzin, V., Lehane, M., O'Halloran, J., Hartung, E., Giblin, L. M., Lynch, P. J., Vaughan, P., Censier, K., Bendixen, D., Comi, G., Heytens, L., Monsieurs, K., Fagerlund, T., Wolz, W., Heffron, J. J. A., Muller, C. R., McCarthy, T. V. <strong>Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation.</strong> Am. J. Hum. Genet. 62: 599-609, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9497245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9497245</a>] [<a href="https://doi.org/10.1086/301748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9497245">Manning et al. (1998)</a> identified a heterozygous c.6617C-T transition in the RYR1 gene, resulting in a thr2206-to-met (T2206M) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9497245" 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="#87" class="mim-tip-reference" title="Wehner, M., Rueffert, H., Koenig, F., Neuhaus, J., Olthoff, D. <strong>Increased sensitivity to 4-chloro-m-cresol and caffeine in primary myotubes from malignant hyperthermia susceptible individuals carrying the ryanodine receptor 1 thr2206met (C6617T) mutation.</strong> Clin. Genet. 62: 135-146, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12220451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12220451</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2002.620206.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12220451">Wehner et al. (2002)</a> identified the T2206M mutation in patients with MHS. Myotubes derived from individuals with the T2206M mutation had an abnormal response of the intracellular calcium concentration to 4-chloro-m-cresol and to caffeine. In myotubes, the EC50 for 4-chloro-m-cresol and for caffeine was reduced strikingly, indicating that this mutation is pathogenic for malignant hyperthermia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12220451" 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>King-Denborough Syndrome</em></strong></p><p>
|
|
In a 6-year-old boy (patient 1) with King-Denborough syndrome (KDS; <a href="/entry/619542">619542</a>), <a href="#15" class="mim-tip-reference" title="Dowling, J. J., Lillis S., Amburgey, K., Zhou, H., Al-Sarraj, S., Buk, S. J. A., Wraige, E., Chow, G., Abbs, S., Leber, S., Lachlan, K., Baralle, D., Taylor, A., Sewry, C., Muntoni, F., Jungbluth, H. <strong>King-Denborough syndrome with and without mutations in the skeletal muscle ryanodine receptor (RYR1) gene.</strong> Neuromusc. Disord. 21: 420-427, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21514828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21514828</a>] [<a href="https://doi.org/10.1016/j.nmd.2011.03.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21514828">Dowling et al. (2011)</a> identified heterozygosity for the c.6617C-T transition in exon 40 of the RYR1 gene, resulting in a T2206M substitution. The mutation was identified by RYR1 gene sequencing. Western blot analysis in patient muscle tissue showed an 84% reduction in RyR1 protein level compared to control. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21514828" 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="0015" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, THR4826ILE
|
|
</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> rs121918595 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918595;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/rs121918595?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=rs121918595" 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=rs121918595" 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=RCV000013847 OR RCV000119520 OR RCV001787768 OR RCV001787769 OR RCV001787770 OR RCV001787771 OR RCV001787772 OR RCV001787773 OR RCV001787774 OR RCV003591630" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013847, RCV000119520, RCV001787768, RCV001787769, RCV001787770, RCV001787771, RCV001787772, RCV001787773, RCV001787774, RCV003591630" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013847...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#9" class="mim-tip-reference" title="Brown, R. L., Pollock, A. N., Couchman, K. G., Hodges, M., Hutchinson, D. O., Waaka, R., Lynch, P., McCarthy, T. V., Stowell, K. M. <strong>A novel ryanodine receptor mutation and genotype-phenotype correlation in a large malignant hyperthermia New Zealand Maori pedigree.</strong> Hum. Molec. Genet. 9: 1515-1524, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10888602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10888602</a>] [<a href="https://doi.org/10.1093/hmg/9.10.1515" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10888602">Brown et al. (2000)</a> reported a large Maori pedigree consisting of 5 probands who experienced clinical episodes of malignant hyperthermia (MHS1; <a href="/entry/145600">145600</a>) and 130 members diagnosed by in vitro contracture testing (IVCT). Sequencing of RYR1 cDNA in an affected individual from this pedigree identified a novel heterozygous c.14477C-T transition, resulting in a thr4826-to-ile (T4826I) substitution in the C-terminal region/transmembrane loop of the skeletal muscle ryanodine receptor. This was the first mutation in the RYR1 C-terminal region associated solely with MHS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10888602" 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="0016" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT, WITH SUSCEPTIBILITY TO MALIGNANT HYPERTHERMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, TYR4796CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118192167 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192167;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=rs118192167" 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=rs118192167" 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=RCV000013848 OR RCV000013849 OR RCV000119509 OR RCV001060960 OR RCV001787775 OR RCV001787776 OR RCV001787777 OR RCV001787778 OR RCV001787779 OR RCV001787780 OR RCV001787781" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013848, RCV000013849, RCV000119509, RCV001060960, RCV001787775, RCV001787776, RCV001787777, RCV001787778, RCV001787779, RCV001787780, RCV001787781" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013848...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 affected members of a 3-generation French family with congenital myopathy-1A (CMYO1A; <a href="/entry/117000">117000</a>), <a href="#58" class="mim-tip-reference" title="Monnier, N., Romero, N. B., Lerale, J., Nivoche, Y., Qi, D., MacLennan, D. H., Fardeau, M., Lunardi, J. <strong>An autosomal dominant congenital myopathy with cores and rods is associated with a neomutation in the RYR1 gene encoding the skeletal muscle ryanodine receptor.</strong> Hum. Molec. Genet. 9: 2599-2608, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11063719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11063719</a>] [<a href="https://doi.org/10.1093/hmg/9.18.2599" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11063719">Monnier et al. (2000)</a> identified a heterozygous c.14387G-A transition in exon 100 of the RYR1 gene, resulting in a tyr4796-to-cys (Y4796C) substitution in the C-terminal channel-forming domain of the RYR1 protein. Expression of the mutant RYR1 cDNA in rabbit HEK293 cells produced channels with increased caffeine sensitivity, cells with increased resting cytoplasmic Ca(2+) levels, and a significantly reduced maximal level of Ca(2+) release, suggesting an increased rate of Ca(2+) leakage in the mutant channel. The authors hypothesized that the resulting chronic elevation in myoplasmic Ca(2+) concentration may be responsible for the severe phenotype in this family. Haplotype analysis indicated that the mutation arose de novo in the proband. Testing of skeletal muscle from the proband showed susceptibility to malignant hyperthermia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11063719" 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="0017" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, GLU2347DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121918596 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918596;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=rs121918596" 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=rs121918596" 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=RCV000013850 OR RCV000119679 OR RCV000171131 OR RCV001384027 OR RCV001787979 OR RCV001787980 OR RCV001787981 OR RCV001787982 OR RCV001787983 OR RCV001787984 OR RCV001787985" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013850, RCV000119679, RCV000171131, RCV001384027, RCV001787979, RCV001787980, RCV001787981, RCV001787982, RCV001787983, RCV001787984, RCV001787985" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013850...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 2 unrelated families with malignant hyperthermia (MHS1; <a href="/entry/145600">145600</a>), <a href="#72" class="mim-tip-reference" title="Sambuughin, N., McWilliams, S., de Bantel, A., Sivakumar, K., Nelson, T. E. <strong>Single-amino-acid deletion in the RYR1 gene, associated with malignant hyperthermia susceptibility and unusual contraction phenotype.</strong> Am. J. Hum. Genet. 69: 204-208, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11389482/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11389482</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11389482[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/10.1086/321270" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11389482">Sambuughin et al. (2001)</a> identified a heterozygous 3-bp deletion (GGA) in exon 44 of the RYR1 gene, resulting in deletion of the conserved glutamic acid at position 2347. The deletion of glu2347 was accompanied by an unusually large electrically evoked contraction tension in the in vitro diagnostic pharmacologic contracture test in MH-positive persons, suggesting that this deletion produces an alteration in skeletal muscle calcium regulation, even in the absence of pharmacologic agents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11389482" 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="0018" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, 9-BP DEL, NT12640
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118192165 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192165;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=rs118192165" 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=rs118192165" 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=RCV000013851 OR RCV000119463" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013851, RCV000119463" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013851...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a 4-generation family (CCD10) with autosomal dominant congenital myopathy-1A (CMYO1A; <a href="/entry/117000">117000</a>), <a href="#57" class="mim-tip-reference" title="Monnier, N., Romero, N. B., Lerale, J., Landrieu, P., Nivoche, Y., Fardeau, M., Lunardi, J. <strong>Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor.</strong> Hum. Molec. Genet. 10: 2581-2592, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709545</a>] [<a href="https://doi.org/10.1093/hmg/10.22.2581" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11709545">Monnier et al. (2001)</a> identified a heterozygous 9-bp deletion (amino acids 12640-12648, 12640delCGCCAGTTC) in exon 91 of the RYR1 gene, eliminating the codons for arg4214, gln4215, and phe4216 from the transcript. The authors noted that these 3 amino acids are conserved among all 3 human RYR genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709545" 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="0019" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, ARG4861HIS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs63749869 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs63749869;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=rs63749869" 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=rs63749869" 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=RCV000013852 OR RCV000119533 OR RCV000534187 OR RCV000851296 OR RCV001787782 OR RCV001787783 OR RCV001787784 OR RCV001787785 OR RCV001787786 OR RCV001787787 OR RCV001787788 OR RCV004017241 OR RCV004991972" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013852, RCV000119533, RCV000534187, RCV000851296, RCV001787782, RCV001787783, RCV001787784, RCV001787785, RCV001787786, RCV001787787, RCV001787788, RCV004017241, RCV004991972" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013852...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Among 7 of 25 unrelated individuals with congenital myopathy-1A (CMYO1A; <a href="/entry/117000">117000</a>) with central cores on muscle biopsy, <a href="#81" class="mim-tip-reference" title="Tilgen, N., Zorzato, F., Halliger-Keller, B., Muntoni, F., Sewry, C., Palumucci, L. M., Schneider, C., Hauser, E., Lehmann-Horn, F., Muller, C. R., Treves, S. <strong>Identification of four novel mutations in the C-terminal membrane spanning domain of the ryanodine receptor 1: association with central core disease and alteration of calcium homeostasis.</strong> Hum. Molec. Genet. 10: 2879-2887, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741831</a>] [<a href="https://doi.org/10.1093/hmg/10.25.2879" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11741831">Tilgen et al. (2001)</a> identified a heterozygous c.14582G-A transition in the RYR1 gene, resulting in an arg4861-to-his (R4861H) substitution at a highly conserved residue in the C-terminal region of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11741831" 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 affected members of 2 unrelated families (CCD07 and CCD15) and an unrelated patient (CCD09) with CMYO1A, <a href="#57" class="mim-tip-reference" title="Monnier, N., Romero, N. B., Lerale, J., Landrieu, P., Nivoche, Y., Fardeau, M., Lunardi, J. <strong>Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor.</strong> Hum. Molec. Genet. 10: 2581-2592, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709545</a>] [<a href="https://doi.org/10.1093/hmg/10.22.2581" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11709545">Monnier et al. (2001)</a> identified a heterozygous R4861H mutation in exon 101 of the RYR1 gene. The mutation occurred de novo in patient CCD09. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709545" 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="#68" class="mim-tip-reference" title="Quinlivan, R. M., Muller, C. R., Davis, M., Laing, N. G., Evans, G. A., Dwyer, J., Dove, J., Roberts, A. P., Sewry, C. A. <strong>Central core disease: clinical, pathological, and genetic features.</strong> Arch. Dis. Child. 88: 1051-1055, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14670767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14670767</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14670767[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/adc.88.12.1051" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14670767">Quinlivan et al. (2003)</a> identified a de novo heterozygous R4861H mutation in exon 101 of the RYR1 gene in an 11-year-old boy (family D) with CMYO1A. Functional studies of the variant were not performed. As an infant, he had hypotonia with poor feeding. He later showed delayed motor development, inability to walk independently, congenital hip dislocation, lordosis, and upper limb involvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14670767" 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="#73" class="mim-tip-reference" title="Sato, I., Wu, S., Ibarra, M. C. A., Hayashi, Y. K., Fujita, H., Tojo, M., Oh, S. J., Nonaka, I., Noguchi, S., Nishino, I. <strong>Congenital neuromuscular disease with uniform type 1 fiber and RYR1 mutation.</strong> Neurology 70: 114-122, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17538032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17538032</a>] [<a href="https://doi.org/10.1212/01.wnl.0000269792.63927.86" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17538032">Sato et al. (2008)</a> identified heterozygosity for the R4861H mutation in a 6-month-old Japanese boy (patient 2) with CMYO1A manifest as 'congenital neuromuscular disease with uniform type 1 fiber' (CNMDU1). He had poor sucking, muscle weakness, joint contractures, and 99.9% type 1 muscle fibers on skeletal muscle biopsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17538032" 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="0020" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 MOVED TO <a href="/entry/180901#0012">180901.0012</a></strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0021" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, PRO3527SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118192164 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192164;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=rs118192164" 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=rs118192164" 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=RCV000119413 OR RCV004558247" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000119413, RCV004558247" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000119413...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a consanguineous Algerian family (family 1) with autosomal recessive congenital myopathy-1B (CMYO1B; <a href="/entry/255320">255320</a>) characterized by the presence of multiple, short-length core lesions (minicores) in both muscle fiber types, <a href="#28" class="mim-tip-reference" title="Ferreiro, A., Monnier, N., Romero, N. B., Leroy, J.-P., Bonnemann, C., Haenggeli, C.-A., Straub, V., Voss, W. D., Nivoche, Y., Jungbluth, H., Lemainque, A., Voit, T., Lunardi, J., Fardeau, M., Guicheney, P. <strong>A recessive form of central core disease, transiently presenting as multi-minicore disease, is associated with a homozygous mutation in the ryanodine receptor type 1 gene.</strong> Ann. Neurol. 51: 750-759, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12112081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12112081</a>] [<a href="https://doi.org/10.1002/ana.10231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12112081">Ferreiro et al. (2002)</a> identified homozygosity for a c.10579C-T transition in exon 71 of the RYR1 gene that resulted in a pro3527-to-ser (P3527S) substitution. Three children in the family presented in infancy with moderate weakness predominant in axial muscles, pelvic girdle and hands, joint hyperlaxity, hand involvement, and multiple minicores on skeletal muscle biopsy. New muscle biopsies from the 3 patients in adulthood demonstrated central core disease with rods; no cores were found in the healthy parents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12112081" 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="0022" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, VAL4849ILE
|
|
</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> rs118192168 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192168;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/rs118192168?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=rs118192168" 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=rs118192168" 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=RCV000013856 OR RCV000119527 OR RCV000990211 OR RCV001060435 OR RCV001787789 OR RCV001787790 OR RCV001787791 OR RCV001787792 OR RCV001787793 OR RCV001787794 OR RCV001787795 OR RCV004017242 OR RCV004586004 OR RCV004658962 OR RCV004786258" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013856, RCV000119527, RCV000990211, RCV001060435, RCV001787789, RCV001787790, RCV001787791, RCV001787792, RCV001787793, RCV001787794, RCV001787795, RCV004017242, RCV004586004, RCV004658962, RCV004786258" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013856...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 19-year-old girl, born of consanguineous parents (family 1), with autosomal recessive congenital myopathy-1B (CMYO1B; <a href="/entry/255320">255320</a>) with both multiminicores and cores on muscle biopsy and confirmed linkage to the RYR1 locus, <a href="#39" class="mim-tip-reference" title="Jungbluth, H., Muller, C. R., Halliger-Keller, B., Brockington, M., Brown, S. C., Feng, L., Chattopadhyay, A., Mercuri, E., Manzur, A. Y., Ferreiro, A., Laing, N. G., Davis, M. R., Roper, H. P., Dubowitz, V., Bydder, G., Sewry, C. A., Muntoni, F. <strong>Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores.</strong> Neurology 59: 284-287, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12136074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12136074</a>] [<a href="https://doi.org/10.1212/wnl.59.2.284" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12136074">Jungbluth et al. (2002)</a> identified a homozygous c.14545G-A transition in exon 101 of the RYR1 gene, resulting in a val4849-to-ile (V4849I) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12136074" 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 a 9-year-old girl, born of consanguineous parents, with autosomal recessive CMYO1B and central core disease on muscle biopsy, <a href="#43" class="mim-tip-reference" title="Kossugue, P. M., Paim, J. F., Navarro, M. M., Silva, H. C., Pavanello, R. C. M., Gurgel-Giannetti, J., Zatz, M., Vainzof, M. <strong>Central core disease due to recessive mutations in RYR1 gene: is it more common than described?</strong> Muscle Nerve 35: 670-674, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17226826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17226826</a>] [<a href="https://doi.org/10.1002/mus.20715" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17226826">Kossugue et al. (2007)</a> identified a homozygous V4849I substitution in the RYR1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17226826" 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="#56" class="mim-tip-reference" title="Monnier, N., Marty, I., Faure, J., Castiglioni, C., Desnuelle, C., Sacconi, S., Estournet, B., Ferreiro, A., Romero, N., Laquerriere, A., Lazaro, L., Martin, J.-J., Morava, E., Rossi, A., Van der Kooi, A., de Visser, M., Verschuuren, C., Lunardi, J. <strong>Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.</strong> Hum. Mutat. 29: 670-678, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18253926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18253926</a>] [<a href="https://doi.org/10.1002/humu.20696" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18253926">Monnier et al. (2008)</a> reported a 9-year-old Dutch boy with a severe autosomal recessive myopathy with ptosis and facial diplegia associated with compound heterozygous mutations in the RYR1 gene: V4849I and a 4-bp insertion (<a href="#0032">180901.0032</a>). The patient had severe neonatal hypotonia, delayed motor development, amyotrophy, kyphoscoliosis, required ventilatory assistance at age 4 years, and was never able to walk. A sister had died at age 5 years of myopathic respiratory insufficiency. <a href="#56" class="mim-tip-reference" title="Monnier, N., Marty, I., Faure, J., Castiglioni, C., Desnuelle, C., Sacconi, S., Estournet, B., Ferreiro, A., Romero, N., Laquerriere, A., Lazaro, L., Martin, J.-J., Morava, E., Rossi, A., Van der Kooi, A., de Visser, M., Verschuuren, C., Lunardi, J. <strong>Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.</strong> Hum. Mutat. 29: 670-678, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18253926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18253926</a>] [<a href="https://doi.org/10.1002/humu.20696" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18253926">Monnier et al. (2008)</a> postulated that since the patient had a hypomorphic frameshift RYR1 allele, the resultant phenotype was more severe compared to those patients with homozygous V4849I mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18253926" 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="0023" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, ARG2676TRP AND THR2787SER
|
|
</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> rs193922826 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193922826;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/rs193922826?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=rs193922826" 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=rs193922826" 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> rs35180584 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs35180584;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/rs35180584?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=rs35180584" 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=rs35180584" 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=RCV000013857 OR RCV000119737 OR RCV000119746 OR RCV000147446 OR RCV000202878 OR RCV000209984 OR RCV000335435 OR RCV000392959 OR RCV000403812 OR RCV000817589 OR RCV001079361 OR RCV001802876 OR RCV001802881 OR RCV002288603 OR RCV002498553" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013857, RCV000119737, RCV000119746, RCV000147446, RCV000202878, RCV000209984, RCV000335435, RCV000392959, RCV000403812, RCV000817589, RCV001079361, RCV001802876, RCV001802881, RCV002288603, RCV002498553" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013857...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with susceptibility to malignant hyperthermia (MHS1; <a href="/entry/145600">145600</a>), <a href="#33" class="mim-tip-reference" title="Guis, S., Figarella-Branger, D., Monnier, N., Bendahan, D., Kozak-Ribbens, G., Mattei, J.-P., Lunardi, J., Cozzone, P. J., Pellissier, J.-F. <strong>Multiminicore disease in a family susceptible to malignant hyperthermia: histology, in vitro contracture tests, and genetic characterization.</strong> Arch. Neurol. 61: 106-113, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14732627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14732627</a>] [<a href="https://doi.org/10.1001/archneur.61.1.106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14732627">Guis et al. (2004)</a> identified heterozygosity for 2 mutations in the RYR1 gene on the same allele: an c.8026C-T transition in exon 50, resulting in an arg2676-to-trp (R2676W) substitution, and an c.8160C-G transversion in exon 53, resulting in a thr2787-to-ser (T2787S) substitution. Affected members of the family had an unusual clinical phenotype including multiminicore myopathy without clinical muscle involvement. <a href="#33" class="mim-tip-reference" title="Guis, S., Figarella-Branger, D., Monnier, N., Bendahan, D., Kozak-Ribbens, G., Mattei, J.-P., Lunardi, J., Cozzone, P. J., Pellissier, J.-F. <strong>Multiminicore disease in a family susceptible to malignant hyperthermia: histology, in vitro contracture tests, and genetic characterization.</strong> Arch. Neurol. 61: 106-113, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14732627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14732627</a>] [<a href="https://doi.org/10.1001/archneur.61.1.106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14732627">Guis et al. (2004)</a> suggested that the R2676W mutation is the candidate mutation responsible for MHS and that the T2787S mutation is a 'secondary aggravating' mutation leading to histologic multiminicores. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14732627" 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="0024" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, 18-BP DEL, NT14588
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118192169 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192169;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=rs118192169" 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=rs118192169" 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=RCV000013858" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013858" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013858</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In DNA from a patient with congenital myopathy-1A (CMYO1A; <a href="/entry/117000">117000</a>), <a href="#95" class="mim-tip-reference" title="Zorzato, F., Yamaguchi, N., Xu, L., Meissner, G., Muller, C. R., Pouliquin, P., Muntoni, F., Sewry, C., Girard, T., Treves, S. <strong>Clinical and functional effects of a deletion in a COOH-terminal lumenal loop of the skeletal muscle ryanodine receptor.</strong> Hum. Molec. Genet. 12: 379-388, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12566385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12566385</a>] [<a href="https://doi.org/10.1093/hmg/ddg032" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12566385">Zorzato et al. (2003)</a> detected a heterozygous deletion of nucleotides 14588 to 14606 in exon 101 of the RYR1 gene. The deletion was also detected in the patient's mildly affected mother. The deletion was predicted to result in the deletion of 7 amino acids (4863-4869, FYNKSED) and insertion of a novel tyrosine residue in the pore-forming region of the sarcoplasmic reticulum calcium release channel. Heterologous expression of recombinant RYR1 peptides and analysis of their membrane topology demonstrated that the deleted amino acids are localized in the luminal loop connecting membrane-spanning segments M8 and M10. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12566385" 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="0025" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, 119-BP INS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193922886 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193922886;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=rs193922886" 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=rs193922886" 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=RCV000013859 OR RCV000119539" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013859, RCV000119539" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013859...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 17-year-old Tunisian boy, born of first-cousin parents, with congenital myopathy-1B (CMYO1B; <a href="/entry/255320">255320</a>) manifest as multiminicore disease with ophthalmoplegia, <a href="#54" class="mim-tip-reference" title="Monnier, N., Ferreiro, A., Marty, I., Labarre-Vila, A., Mezin, P., Lunardi, J. <strong>A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia.</strong> Hum. Molec. Genet. 12: 1171-1178, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12719381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12719381</a>] [<a href="https://doi.org/10.1093/hmg/ddg121" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12719381">Monnier et al. (2003)</a> identified a homozygous 119-bp insertion at position 14646 of the RYR1 gene and an A-to-G transition at position +1 from the insertion fragment, resulting in a frameshift of the last 94 amino acids downstream of the insertion site and a premature stop codon. The mutation, designated 14646+2.99 kb A-to-G, resulted in a 90% decrease of the normal RYR1 transcript in skeletal muscle. The mutation was not expressed in lymphoblastoid cells, suggesting a tissue-specific splicing mechanism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12719381" 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="0026" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, ARG109TRP
|
|
</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> rs118192173 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192173;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/rs118192173?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=rs118192173" 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=rs118192173" 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=RCV000013860 OR RCV000119608 OR RCV000655512 OR RCV001199051 OR RCV003447473 OR RCV003996093 OR RCV004586005 OR RCV005003354" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013860, RCV000119608, RCV000655512, RCV001199051, RCV003447473, RCV003996093, RCV004586005, RCV005003354" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013860...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs with congenital myopathy-1B (CMYO1B; <a href="/entry/255320">255320</a>) manifest as minicore myopathy with external ophthalmoplegia, <a href="#40" class="mim-tip-reference" title="Jungbluth, H., Zhou, H., Hartley, L., Halliger-Keller, B., Messina, S., Longman, C., Brockington, M., Robb, S. A., Straub, V., Voit, T., Swash, M., Ferreiro, A., Bydder, G., Sewry, C. A., Muller, C., Muntoni, F. <strong>Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.</strong> Neurology 65: 1930-1935, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16380615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16380615</a>] [<a href="https://doi.org/10.1212/01.wnl.0000188870.37076.f2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16380615">Jungbluth et al. (2005)</a> identified a c.325C-T transition in exon 4 of the RYR1 gene, resulting in an arg109-to-trp (R109W) substitution in a highly conserved region. Analysis of cDNA showed homozygosity for the mutation, but genomic DNA showed heterozygosity. <a href="#40" class="mim-tip-reference" title="Jungbluth, H., Zhou, H., Hartley, L., Halliger-Keller, B., Messina, S., Longman, C., Brockington, M., Robb, S. A., Straub, V., Voit, T., Swash, M., Ferreiro, A., Bydder, G., Sewry, C. A., Muller, C., Muntoni, F. <strong>Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.</strong> Neurology 65: 1930-1935, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16380615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16380615</a>] [<a href="https://doi.org/10.1212/01.wnl.0000188870.37076.f2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16380615">Jungbluth et al. (2005)</a> postulated that the second allele was either not expressed or deleted and may indicate a promoter mutation or a large deletion. Haplotype analysis and the unaffected parental carrier status were consistent with biallelic mutations and autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16380615" 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="#42" class="mim-tip-reference" title="Klein, A., Lillis, S., Munteanu, I., Scoto, M., Zhou, H., Quinlivan, R., Straub, V., Manzur, A. Y., Roper, H., Jeannet, P-Y., Rakowicz, W., Jones, D. H., and 20 others. <strong>Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.</strong> Hum. Mutat. 33: 981-988, 2012. Note: Erratum: Hum. Mutat. 33: 1310, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22473935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22473935</a>] [<a href="https://doi.org/10.1002/humu.22056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22473935">Klein et al. (2012)</a> reanalyzed one of these patients as patient 41 and identified an additional missense and nonsense mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22473935" 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="0027" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, MET2423LYS
|
|
</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> rs118192174 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192174;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/rs118192174?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=rs118192174" 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=rs118192174" 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=RCV000013861 OR RCV000119694 OR RCV000415169 OR RCV001197410 OR RCV001851835 OR RCV002504782 OR RCV003996094 OR RCV004017243 OR RCV004813035" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013861, RCV000119694, RCV000415169, RCV001197410, RCV001851835, RCV002504782, RCV003996094, RCV004017243, RCV004813035" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013861...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 sibs with congenital myopathy-1B (CMYO1B; <a href="/entry/255320">255320</a>) manifest as minicore myopathy with external ophthalmoplegia originally reported by <a href="#77" class="mim-tip-reference" title="Swash, M., Schwartz, M. S. <strong>Familial multicore disease with focal loss of cross-striations and ophthalmoplegia.</strong> J. Neurol. Sci. 52: 1-10, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7299413/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7299413</a>] [<a href="https://doi.org/10.1016/0022-510x(81)90129-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7299413">Swash and Schwartz (1981)</a>, <a href="#40" class="mim-tip-reference" title="Jungbluth, H., Zhou, H., Hartley, L., Halliger-Keller, B., Messina, S., Longman, C., Brockington, M., Robb, S. A., Straub, V., Voit, T., Swash, M., Ferreiro, A., Bydder, G., Sewry, C. A., Muller, C., Muntoni, F. <strong>Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.</strong> Neurology 65: 1930-1935, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16380615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16380615</a>] [<a href="https://doi.org/10.1212/01.wnl.0000188870.37076.f2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16380615">Jungbluth et al. (2005)</a> identified a c.7268T-A transversion in exon 45 the RYR1 gene, resulting in a met2423-to-lys substitution in a highly conserved region. Analysis of cDNA showed homozygosity for the mutation, but genomic DNA showed heterozygosity. <a href="#40" class="mim-tip-reference" title="Jungbluth, H., Zhou, H., Hartley, L., Halliger-Keller, B., Messina, S., Longman, C., Brockington, M., Robb, S. A., Straub, V., Voit, T., Swash, M., Ferreiro, A., Bydder, G., Sewry, C. A., Muller, C., Muntoni, F. <strong>Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.</strong> Neurology 65: 1930-1935, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16380615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16380615</a>] [<a href="https://doi.org/10.1212/01.wnl.0000188870.37076.f2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16380615">Jungbluth et al. (2005)</a> postulated that the second allele was either not expressed or deleted and may indicate a promoter mutation or a large deletion. Haplotype analysis and the unaffected parental carrier status were consistent with biallelic mutations and autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7299413+16380615" 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="#42" class="mim-tip-reference" title="Klein, A., Lillis, S., Munteanu, I., Scoto, M., Zhou, H., Quinlivan, R., Straub, V., Manzur, A. Y., Roper, H., Jeannet, P-Y., Rakowicz, W., Jones, D. H., and 20 others. <strong>Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.</strong> Hum. Mutat. 33: 981-988, 2012. Note: Erratum: Hum. Mutat. 33: 1310, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22473935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22473935</a>] [<a href="https://doi.org/10.1002/humu.22056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22473935">Klein et al. (2012)</a> reanalyzed one of these patients as patient 44 and identified a W661X mutation in trans with the M2423 allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22473935" 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="0028" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, IVS99AS, A-T, -2
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193922870 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193922870;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=rs193922870" 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=rs193922870" 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=RCV000013862 OR RCV000119507" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013862, RCV000119507" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013862...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs (family 5) with congenital myopathy-1B (CMYO1B; <a href="/entry/255320">255320</a>) manifest as minicore myopathy with external ophthalmoplegia, <a href="#40" class="mim-tip-reference" title="Jungbluth, H., Zhou, H., Hartley, L., Halliger-Keller, B., Messina, S., Longman, C., Brockington, M., Robb, S. A., Straub, V., Voit, T., Swash, M., Ferreiro, A., Bydder, G., Sewry, C. A., Muller, C., Muntoni, F. <strong>Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.</strong> Neurology 65: 1930-1935, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16380615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16380615</a>] [<a href="https://doi.org/10.1212/01.wnl.0000188870.37076.f2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16380615">Jungbluth et al. (2005)</a> identified compound heterozygosity for 2 mutations in the RYR1 gene: an A-to-T transversion in intron 99 (c.14365-2A-T), resulting in a splice site mutation, and a c.10349C-T transition in exon 68, resulting in a ser3450-to-phe (S3450F) substitution (<a href="#0029">180901.0029</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16380615" 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="0029" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, SER3450PHE
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193922836 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193922836;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=rs193922836" 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=rs193922836" 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=RCV000013863 OR RCV000119408 OR RCV003996095" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013863, RCV000119408, RCV003996095" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013863...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the ser3450-to-phe (S3450F) mutation in the RYR1 gene that was found in 2 sibs with congenital myopathy-1B (CMYO1B; <a href="/entry/255320">255320</a>) by <a href="#40" class="mim-tip-reference" title="Jungbluth, H., Zhou, H., Hartley, L., Halliger-Keller, B., Messina, S., Longman, C., Brockington, M., Robb, S. A., Straub, V., Voit, T., Swash, M., Ferreiro, A., Bydder, G., Sewry, C. A., Muller, C., Muntoni, F. <strong>Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.</strong> Neurology 65: 1930-1935, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16380615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16380615</a>] [<a href="https://doi.org/10.1212/01.wnl.0000188870.37076.f2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16380615">Jungbluth et al. (2005)</a>, see <a href="#0028">180901.0028</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16380615" 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="0030" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, THR4637ALA
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118192166 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192166;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=rs118192166" 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=rs118192166" 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=RCV000013864 OR RCV000119487 OR RCV001824568 OR RCV001851836" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013864, RCV000119487, RCV001824568, RCV001851836" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013864...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a large family with autosomal dominant congenital myopathy-1A (CMYO1A; <a href="/entry/117000">117000</a>), <a href="#74" class="mim-tip-reference" title="Scacheri, P. C., Hoffman, E. P., Fratkin, J. D., Semino-Mora, C., Senchak, A., Davis, M. R., Laing, N. G., Vedanarayanan, V., Subramony, S. H. <strong>A novel ryanodine receptor gene mutation causing both cores and rods in congenital myopathy.</strong> Neurology 55: 1689-1696, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11113224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11113224</a>] [<a href="https://doi.org/10.1212/wnl.55.11.1689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11113224">Scacheri et al. (2000)</a> identified a heterozygous c.13996A-G transition in exon 95 of the RYR1 gene, resulting in a thr4637-to-ala (T4637A) substitution within the transmembrane domain. Skeletal muscle biopsies from 2 affected individuals showed the presence of central cores in over 85% of myofibers and nemaline rods in 5 to 25% of myofibers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11113224" 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="0031" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, TYR522SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118192162 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192162;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=rs118192162" 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=rs118192162" 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=RCV000013865 OR RCV000119574 OR RCV001787796 OR RCV001787797 OR RCV001787798 OR RCV001787799 OR RCV001787800 OR RCV001787801 OR RCV001787802" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013865, RCV000119574, RCV001787796, RCV001787797, RCV001787798, RCV001787799, RCV001787800, RCV001787801, RCV001787802" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013865...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a French family with malignant hyperthermia (MHS1; <a href="/entry/145600">145600</a>), <a href="#66" class="mim-tip-reference" title="Quane, K. A., Keating, K. E., Healy, J. M. S., Manning, B. M., Krivosic-Horber, R., Krivosic, I., Monnier, N., Lunardi, J., McCarthy, T. V. <strong>Mutation screening of the RYR1 gene in malignant hyperthermia: detection of a novel tyr to ser mutation in a pedigree with associated central cores.</strong> Genomics 23: 236-239, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7829078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7829078</a>] [<a href="https://doi.org/10.1006/geno.1994.1483" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7829078">Quane et al. (1994)</a> identified a heterozygous c.1565A-C transversion in the RYR1 gene, resulting in a tyr522-to-ser (Y522S) substitution. Skeletal muscle biopsies from 2 patients in this family showed central cores in the absence of clinical features of a myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7829078" 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="0032" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0032 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, 4-BP INS, 1742ATCA
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193922771 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193922771;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=rs193922771" 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=rs193922771" 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=RCV000013867 OR RCV000119584 OR RCV003591631" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013867, RCV000119584, RCV003591631" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013867...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 9-year-old Dutch boy with a severe form of autosomal recessive congenital myopathy-1B (CMYO1B; <a href="/entry/255320">255320</a>), <a href="#56" class="mim-tip-reference" title="Monnier, N., Marty, I., Faure, J., Castiglioni, C., Desnuelle, C., Sacconi, S., Estournet, B., Ferreiro, A., Romero, N., Laquerriere, A., Lazaro, L., Martin, J.-J., Morava, E., Rossi, A., Van der Kooi, A., de Visser, M., Verschuuren, C., Lunardi, J. <strong>Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.</strong> Hum. Mutat. 29: 670-678, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18253926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18253926</a>] [<a href="https://doi.org/10.1002/humu.20696" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18253926">Monnier et al. (2008)</a> detected compound heterozygous mutations in the RYR1 gene: V4849I (<a href="#0022">180901.0022</a>) and a 4-bp insertion (c.1742insATCA). The patient had severe neonatal hypotonia, delayed motor development, amyotrophy, kyphoscoliosis, required ventilatory assistance at age 4 years, and was never able to walk. A sister had died at age 5 years of myopathic respiratory insufficiency. The 4-bp insertion was predicted to result in a premature stop codon and an unstable truncated protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18253926" 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="0033" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0033 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, 2-BP DEL/2-BP INS, NT14761
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118192171 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192171;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=rs118192171" 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=rs118192171" 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=RCV000013868 OR RCV000119559 OR RCV002513027" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013868, RCV000119559, RCV002513027" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013868...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 11-year-old Japanese patient with congenital myopathy-1A (CMYO1A; <a href="/entry/117000">117000</a>), <a href="#73" class="mim-tip-reference" title="Sato, I., Wu, S., Ibarra, M. C. A., Hayashi, Y. K., Fujita, H., Tojo, M., Oh, S. J., Nonaka, I., Noguchi, S., Nishino, I. <strong>Congenital neuromuscular disease with uniform type 1 fiber and RYR1 mutation.</strong> Neurology 70: 114-122, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17538032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17538032</a>] [<a href="https://doi.org/10.1212/01.wnl.0000269792.63927.86" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17538032">Sato et al. (2008)</a> identified a heterozygous 2-bp deletion/2-bp insertion (c.14761delTTinsAC) in exon 102 of the RYR1 gene, resulting in a phe4921-to-thr (F4921T) substitution. The patient had delayed motor milestones, proximal muscle weakness, and uniform type 1 fibers on muscle biopsy. The patient's affected father, who carried the same mutation (<a href="#89" class="mim-tip-reference" title="Wu, S., Ibarra M, C. A., Malicdan, M. C. V., Murayama, K., Ichihara, Y., Kikuchi, H., Nonaka, I., Noguchi, S., Hayashi, Y. K., Nishino, I. <strong>Central core disease is due to RYR1 mutations in more than 90% of patients.</strong> Brain 129: 1470-1480, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16621918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16621918</a>] [<a href="https://doi.org/10.1093/brain/awl077" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16621918">Wu et al., 2006</a>), showed typical central cores on muscle biopsy. The family had previously been reported by <a href="#83" class="mim-tip-reference" title="Tojo, M., Ozawa, M., Nonaka, I. <strong>Central core disease and congenital neuromuscular disease with uniform type 1 fibers in one family.</strong> Brain Dev. 22: 262-264, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10838116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10838116</a>] [<a href="https://doi.org/10.1016/s0387-7604(00)00108-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10838116">Tojo et al. (2000)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17538032+16621918+10838116" 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="0034" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0034 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, 20-BP DEL, NT13013
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193922856 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193922856;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=rs193922856" 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=rs193922856" 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=RCV000013870 OR RCV000119472 OR RCV001216605 OR RCV002288489 OR RCV004737151" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013870, RCV000119472, RCV001216605, RCV002288489, RCV004737151" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013870...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 8-year-old Japanese patient (P1) with congenital myopathy-1A (CMYO1A; <a href="/entry/117000">117000</a>), <a href="#73" class="mim-tip-reference" title="Sato, I., Wu, S., Ibarra, M. C. A., Hayashi, Y. K., Fujita, H., Tojo, M., Oh, S. J., Nonaka, I., Noguchi, S., Nishino, I. <strong>Congenital neuromuscular disease with uniform type 1 fiber and RYR1 mutation.</strong> Neurology 70: 114-122, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17538032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17538032</a>] [<a href="https://doi.org/10.1212/01.wnl.0000269792.63927.86" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17538032">Sato et al. (2008)</a> identified a heterozygous 20-bp deletion beginning in exon 91 of the RYR1 gene and predicted to result in premature termination and removal of 464 residues from the C terminus of the protein (Ala4338fs). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17538032" 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="0035" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0035 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, 2-BP DEL, 5726AG AND MET3081THR
|
|
</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> rs147012990 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs147012990;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/rs147012990?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=rs147012990" 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=rs147012990" 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">rs387906681 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906681;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=rs387906681" 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=rs387906681" 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=RCV000022757 OR RCV000210003 OR RCV000253393 OR RCV000300656 OR RCV000357829 OR RCV000404978 OR RCV000721732 OR RCV001086670" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022757, RCV000210003, RCV000253393, RCV000300656, RCV000357829, RCV000404978, RCV000721732, RCV001086670" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022757...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 South African patient (patient 1) with a severe form of autosomal recessive congenital myopathy-1B (CMYO1B; <a href="/entry/255320">255320</a>), <a href="#88" class="mim-tip-reference" title="Wilmshurst, J. M., Lillis, S., Zhou, H., Pillay, K., Henderson, H., Kress, W., Muller, C. R., Ndondo, A., Cloke, V., Cullup, T., Bertini, E., Boennemann, C., and 10 others. <strong>RYR1 mutations are a common cause of congenital myopathies with central nuclei.</strong> Ann. Neurol. 68: 717-726, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20839240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20839240</a>] [<a href="https://doi.org/10.1002/ana.22119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20839240">Wilmshurst et al. (2010)</a> identified compound heterozygosity for 2 alleles containing complex mutations in the RYR1 gene: 1 allele carried a 2-bp deletion (5726delAG) in exon 35 and a 9242T-C transition in exon 63, resulting in a met3081-to-thr (M3081T) substitution, and the other allele carried a splice site mutation and a V4842M substitution (<a href="#0036">180901.0036</a>). The 2-bp del/M3081T allele was also found in patient 12, also South African, in whom a mutation on the second allele was not identified. Haplotype analysis indicated a founder effect in the South African population. The phenotype was characterized by onset at birth, neonatal hypotonia and weakness, delayed motor development, external ophthalmoplegia, and bulbar involvement. Histopathologic findings included central nuclei, multiple internalized nuclei, type 1 fiber predominance and hypotrophy, relative type 2 hypertrophy, and oxidative abnormalities in electron microscopic analysis, although frank cores were not typically seen. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20839240" 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="0036" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0036 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, IVS68AS, C-G, -6 AND VAL4842MET
|
|
</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> rs193922837 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193922837;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/rs193922837?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=rs193922837" 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=rs193922837" 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> rs193922879 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193922879;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/rs193922879?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=rs193922879" 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=rs193922879" 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=RCV000022758 OR RCV000119410 OR RCV000119524 OR RCV000148830 OR RCV000226744 OR RCV000535801 OR RCV000546614 OR RCV000616859 OR RCV000624604 OR RCV001132276 OR RCV001249074 OR RCV001588937 OR RCV001775081 OR RCV002247501 OR RCV002498549 OR RCV003997313 OR RCV004586556 OR RCV004586558 OR RCV004689614 OR RCV005003479" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022758, RCV000119410, RCV000119524, RCV000148830, RCV000226744, RCV000535801, RCV000546614, RCV000616859, RCV000624604, RCV001132276, RCV001249074, RCV001588937, RCV001775081, RCV002247501, RCV002498549, RCV003997313, RCV004586556, RCV004586558, RCV004689614, RCV005003479" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022758...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 11 South African patients with a severe form of autosomal recessive congenital myopathy-1B (CMYO1B; <a href="/entry/255320">255320</a>), <a href="#88" class="mim-tip-reference" title="Wilmshurst, J. M., Lillis, S., Zhou, H., Pillay, K., Henderson, H., Kress, W., Muller, C. R., Ndondo, A., Cloke, V., Cullup, T., Bertini, E., Boennemann, C., and 10 others. <strong>RYR1 mutations are a common cause of congenital myopathies with central nuclei.</strong> Ann. Neurol. 68: 717-726, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20839240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20839240</a>] [<a href="https://doi.org/10.1002/ana.22119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20839240">Wilmshurst et al. (2010)</a> found a common complex allele containing 2 mutations in the RYR1 gene: a C-to-G transversion in intron 68 (10348-6C-G) and a 14524G-A transition in exon 101, resulting in a val4842-to-met (V4842M) substitution. The splice site mutation results in the production of an aberrant transcript that includes intron 68 and introduces a premature stop codon (His3449ins33fsTer54), but penetrance of this mutation is incomplete, resulting in the expression of both spliced and unspliced transcripts (<a href="#56" class="mim-tip-reference" title="Monnier, N., Marty, I., Faure, J., Castiglioni, C., Desnuelle, C., Sacconi, S., Estournet, B., Ferreiro, A., Romero, N., Laquerriere, A., Lazaro, L., Martin, J.-J., Morava, E., Rossi, A., Van der Kooi, A., de Visser, M., Verschuuren, C., Lunardi, J. <strong>Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.</strong> Hum. Mutat. 29: 670-678, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18253926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18253926</a>] [<a href="https://doi.org/10.1002/humu.20696" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18253926">Monnier et al., 2008</a>). <a href="#88" class="mim-tip-reference" title="Wilmshurst, J. M., Lillis, S., Zhou, H., Pillay, K., Henderson, H., Kress, W., Muller, C. R., Ndondo, A., Cloke, V., Cullup, T., Bertini, E., Boennemann, C., and 10 others. <strong>RYR1 mutations are a common cause of congenital myopathies with central nuclei.</strong> Ann. Neurol. 68: 717-726, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20839240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20839240</a>] [<a href="https://doi.org/10.1002/ana.22119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20839240">Wilmshurst et al. (2010)</a> hypothesized that this allele determines the phenotype by 2 interrelated mechanisms: by reducing the amount of the RYR1 protein and by the V4842M substitution on residual protein. Haplotype analysis indicated a founder effect in the South African population, but <a href="#56" class="mim-tip-reference" title="Monnier, N., Marty, I., Faure, J., Castiglioni, C., Desnuelle, C., Sacconi, S., Estournet, B., Ferreiro, A., Romero, N., Laquerriere, A., Lazaro, L., Martin, J.-J., Morava, E., Rossi, A., Van der Kooi, A., de Visser, M., Verschuuren, C., Lunardi, J. <strong>Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.</strong> Hum. Mutat. 29: 670-678, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18253926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18253926</a>] [<a href="https://doi.org/10.1002/humu.20696" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18253926">Monnier et al. (2008)</a> also found it in 2 sibs from Chile with severe neonatal hypotonia. All except 1 of the 11 patients were compound heterozygous for this allele and another pathogenic allele affecting the RYR1 gene (see, e.g., <a href="#0035">180901.0035</a> and <a href="#0037">180901.0037</a>). The phenotype was characterized by onset at birth, neonatal hypotonia and weakness, delayed motor development, external ophthalmoplegia, and bulbar involvement. Histopathologic findings included central nuclei, multiple internalized nuclei, type 1 fiber predominance and hypotrophy, relative type 2 hypertrophy, and oxidative abnormalities in electron microscopic analysis, although frank cores were not typically seen. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18253926+20839240" 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="0037" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0037 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, 2-BP DEL, 8342TA AND HIS3981TYR
|
|
</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> rs148772854 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs148772854;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/rs148772854?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=rs148772854" 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=rs148772854" 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> rs758580075 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs758580075;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/rs758580075?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=rs758580075" 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=rs758580075" 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=RCV000022759 OR RCV000079122 OR RCV000327345 OR RCV000333023 OR RCV000389868 OR RCV000515090 OR RCV000721705 OR RCV001081494 OR RCV001209505 OR RCV002535011 OR RCV003388645 OR RCV003514405 OR RCV004586901 OR RCV005004388" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022759, RCV000079122, RCV000327345, RCV000333023, RCV000389868, RCV000515090, RCV000721705, RCV001081494, RCV001209505, RCV002535011, RCV003388645, RCV003514405, RCV004586901, RCV005004388" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022759...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 South African patients with a severe form of autosomal recessive congenital myopathy-1B (CMYO1B; <a href="/entry/255320">255320</a>), <a href="#88" class="mim-tip-reference" title="Wilmshurst, J. M., Lillis, S., Zhou, H., Pillay, K., Henderson, H., Kress, W., Muller, C. R., Ndondo, A., Cloke, V., Cullup, T., Bertini, E., Boennemann, C., and 10 others. <strong>RYR1 mutations are a common cause of congenital myopathies with central nuclei.</strong> Ann. Neurol. 68: 717-726, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20839240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20839240</a>] [<a href="https://doi.org/10.1002/ana.22119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20839240">Wilmshurst et al. (2010)</a> identified compound heterozygosity for 2 alleles containing complex mutations in the RYR1 gene: 1 allele carried a 2-bp deletion in exon 53 (8342delTA) and a 11941C-T transition in exon 87, resulting in a his3981-to-tyr (H3981Y) substitution, and the other allele carried a splice site mutation and a V4842M substitution (<a href="#0036">180901.0036</a>). Haplotype analysis indicated a founder effect in the South African population. The phenotype was characterized by onset at birth, neonatal hypotonia and weakness, delayed motor development, external ophthalmoplegia, and bulbar involvement. Histopathologic findings included central nuclei, multiple internalized nuclei, type 1 fiber predominance and hypotrophy, relative type 2 hypertrophy, and oxidative abnormalities in electron microscopic analysis, although frank cores were not typically seen. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20839240" 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="0038" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0038 KING-DENBOROUGH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, LYS33GLU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193922746 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193922746;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=rs193922746" 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=rs193922746" 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=RCV000049252 OR RCV000119774 OR RCV001588881 OR RCV003591651" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000049252, RCV000119774, RCV001588881, RCV003591651" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000049252...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 27-year-old woman with King-Denborough syndrome (KDS; <a href="/entry/619542">619542</a>), <a href="#13" class="mim-tip-reference" title="D'Arcy, C. E., Bjorksten, A., Yiu, E. M., Bankier, A., Gillies, R., McLean, C. A., Shield, L. K., Ryan, M. M. <strong>King-Denborough syndrome caused by a novel mutation in the ryanodine receptor gene.</strong> Neurology 71: 776-777, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18765655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18765655</a>] [<a href="https://doi.org/10.1212/01.wnl.0000324929.33780.2f" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18765655">D'Arcy et al. (2008)</a> identified a heterozygous c.97A-G transition in exon 2 of the RYR1 gene, resulting in a lys33-to-glu (K33E) substitution at a highly conserved residue. The mutation was not present in other family members or in 200 normal controls. She was born at term after a pregnancy complicated by decreased fetal movements and breech presentation. At birth, she was noted to have hypotonia, ptosis, high-arched palate, prominent philtrum, and scaphocephaly. The father and paternal grandfather had congenital ptosis, but no other signs of neuromuscular disease. She underwent surgery for ptosis at ages 2 and 9 years without complications. Facial and proximal limb weakness became more apparent with age, and she developed kyphoscoliosis, myopathic facies with flat midface, prominent columella, and webbed neck. An EMG was myopathic and serum creatine kinase was increased. At age 15 years, she developed hyperthermia during surgery for scoliosis repair, and subsequent muscle testing confirmed susceptibility to malignant hyperthermia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18765655" 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="0039" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0039 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, ARG2241TER (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs200563280;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs200563280</a>)
|
|
</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> rs200563280 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs200563280;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/rs200563280?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=rs200563280" 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=rs200563280" 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=RCV000147436 OR RCV000148787 OR RCV000171129 OR RCV000178453 OR RCV000263175 OR RCV000525302 OR RCV001257398 OR RCV001530191 OR RCV002505131" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000147436, RCV000148787, RCV000171129, RCV000178453, RCV000263175, RCV000525302, RCV001257398, RCV001530191, RCV002505131" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000147436...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 6 fetuses, conceived by consanguineous Dutch parents, with congenital myopathy-1B (CMYO1B; <a href="/entry/255320">255320</a>) presenting as lethal fetal akinesia, <a href="#53" class="mim-tip-reference" title="McKie, A. B., Alsaedi, A., Vogt, J., Stuurman, K. E., Weiss, M. M., Shakeel, H., Tee, L., Morgan, N. V., Nikkels, P. G. J., van Haaften, G., Park, S.-M., van der Smagt, J. J., Bugiani, M., Maher, E. R. <strong>Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome.</strong> Acta Neuropath. Commun. 2: 148, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25476234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25476234</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25476234[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/10.1186/s40478-014-0148-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25476234">McKie et al. (2014)</a> identified a homozygous c.6721C-T transition (c.6721C-T, NM_000540.2) in the RYR1 gene, resulting in an arg2241-to-ter (R2241X) substitution. The mutation, which was found by homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. A heterozygous c.6721C-T transition (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs200563280;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs200563280</a>) had been found in 1 of 6,503 genotypes in the Exome Variant Server database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25476234" 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="0040" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0040 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, 27-BP DEL, NT2097
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs876661306 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs876661306;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=rs876661306" 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=rs876661306" 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=RCV000171130" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000171130" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000171130</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 fetuses, conceived by consanguineous Pakistani parents, with congenital myopathy-1B (CMYO1B; <a href="/entry/255320">255320</a>) presenting as lethal fetal akinesia, <a href="#53" class="mim-tip-reference" title="McKie, A. B., Alsaedi, A., Vogt, J., Stuurman, K. E., Weiss, M. M., Shakeel, H., Tee, L., Morgan, N. V., Nikkels, P. G. J., van Haaften, G., Park, S.-M., van der Smagt, J. J., Bugiani, M., Maher, E. R. <strong>Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome.</strong> Acta Neuropath. Commun. 2: 148, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25476234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25476234</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25476234[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/10.1186/s40478-014-0148-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25476234">McKie et al. (2014)</a> identified a homozygous 27-bp deletion (c.2097_2123del, NM_000540.2) in the RYR1 gene that removes 9 conserved amino acids from the SPRY2 domain and replaces glu699 with asp (glu699_gly707del). Each unaffected parent was heterozygous for the mutation. The family was 1 of 36 with a similar lethal phenotype who underwent direct sequencing of the RYR1 gene. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25476234" 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="0041" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0041 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, 3-BP DEL, 7043GAG (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918596;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs121918596</a>)
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000013850 OR RCV000119679 OR RCV000171131 OR RCV001384027 OR RCV001787979 OR RCV001787980 OR RCV001787981 OR RCV001787982 OR RCV001787983 OR RCV001787984 OR RCV001787985" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013850, RCV000119679, RCV000171131, RCV001384027, RCV001787979, RCV001787980, RCV001787981, RCV001787982, RCV001787983, RCV001787984, RCV001787985" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013850...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 fetuses, conceived of consanguineous Palestinian parents, with congenital myopathy-1B (CMYO1B; <a href="/entry/255320">255320</a>) presenting as lethal fetal akinesia, <a href="#53" class="mim-tip-reference" title="McKie, A. B., Alsaedi, A., Vogt, J., Stuurman, K. E., Weiss, M. M., Shakeel, H., Tee, L., Morgan, N. V., Nikkels, P. G. J., van Haaften, G., Park, S.-M., van der Smagt, J. J., Bugiani, M., Maher, E. R. <strong>Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome.</strong> Acta Neuropath. Commun. 2: 148, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25476234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25476234</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25476234[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/10.1186/s40478-014-0148-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25476234">McKie et al. (2014)</a> identified a homozygous 3-bp deletion (c.7043_7045delGAG, NM_000540.2) in the RYR1 gene, resulting in the deletion of the conserved residue glu2347 (E2347del). Each unaffected parent was heterozygous for the mutation. The family was 1 of 36 with a similar phenotype who underwent direct sequencing of the RYR1 gene. Functional studies of the variant were not performed. A different 3-bp deletion results in the deletion of the same residue (<a href="#0017">180901.0017</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25476234" 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="0042" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0042 KING-DENBOROUGH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, ARG2452TRP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118192124 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192124;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=rs118192124" 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=rs118192124" 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=RCV000056226 OR RCV000119706 OR RCV000527240 OR RCV001729374 OR RCV001787847 OR RCV001787848 OR RCV001787849 OR RCV001787850 OR RCV001787851 OR RCV001787852 OR RCV001787853 OR RCV002221195 OR RCV002281899" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056226, RCV000119706, RCV000527240, RCV001729374, RCV001787847, RCV001787848, RCV001787849, RCV001787850, RCV001787851, RCV001787852, RCV001787853, RCV002221195, RCV002281899" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056226...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 14-year-old proband (patient 2) with King-Denborough syndrome (KDS; <a href="/entry/619542">619542</a>), <a href="#15" class="mim-tip-reference" title="Dowling, J. J., Lillis S., Amburgey, K., Zhou, H., Al-Sarraj, S., Buk, S. J. A., Wraige, E., Chow, G., Abbs, S., Leber, S., Lachlan, K., Baralle, D., Taylor, A., Sewry, C., Muntoni, F., Jungbluth, H. <strong>King-Denborough syndrome with and without mutations in the skeletal muscle ryanodine receptor (RYR1) gene.</strong> Neuromusc. Disord. 21: 420-427, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21514828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21514828</a>] [<a href="https://doi.org/10.1016/j.nmd.2011.03.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21514828">Dowling et al. (2011)</a> identified heterozygosity for a c.7354C-T transition in exon 46 of the RYR1 gene, resulting in an arg2452-to-trp (R2452W) substitution at a highly conserved residue. The mutation, which was found by RYR1 gene sequencing, was also identified in the boy's symptomatic mother and sib. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21514828" 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="0043" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0043 KING-DENBOROUGH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, ARG2508CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118192178 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192178;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=rs118192178" 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=rs118192178" 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=RCV000056228 OR RCV000119718 OR RCV000552166 OR RCV000624571 OR RCV001198416 OR RCV001731347 OR RCV001814037 OR RCV002281900" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056228, RCV000119718, RCV000552166, RCV000624571, RCV001198416, RCV001731347, RCV001814037, RCV002281900" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056228...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-year-old boy with King-Denborough syndrome (KDS; <a href="/entry/619542">619542</a>), <a href="#38" class="mim-tip-reference" title="Joseph, M. R., Theroux, M. C., Mooney, J. J., Falitz, S., Brandom, B. W., Byler, D. L. <strong>Intraoperative presentation of malignant hyperthermia (confirmed by RYR1 gene mutation, c.7522C-T; p.R2508C) leads to diagnosis of King-Denborough syndrome in a child with hypotonia and dysmorphic features: a case report.</strong> A. A. Case Rep. 8: 55-57, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27918309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27918309</a>] [<a href="https://doi.org/10.1213/XAA.0000000000000421" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27918309">Joseph et al. (2017)</a> identified heterozygosity for an c.7522C-T transition in the RYR1 gene, resulting in an arg2508-to-cys (R2508C) substitution. The mutation was identified by RYR1 gene sequencing. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27918309" 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="0044" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0044 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, ARG4893TRP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118192150 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192150;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=rs118192150" 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=rs118192150" 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=RCV000056236 OR RCV000119545 OR RCV001046476 OR RCV002496742 OR RCV003996489" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056236, RCV000119545, RCV001046476, RCV002496742, RCV003996489" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056236...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 2 unrelated families (CCD04 and CCD08) with autosomal dominant congenital myopathy-1A (CMYO1A; <a href="/entry/117000">117000</a>), <a href="#57" class="mim-tip-reference" title="Monnier, N., Romero, N. B., Lerale, J., Landrieu, P., Nivoche, Y., Fardeau, M., Lunardi, J. <strong>Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor.</strong> Hum. Molec. Genet. 10: 2581-2592, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709545</a>] [<a href="https://doi.org/10.1093/hmg/10.22.2581" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11709545">Monnier et al. (2001)</a> identified a heterozygous c.14677C-T transition in exon 102 of the RYR1 gene, resulting in an arg4893-to-trp (R4893W) substitution in the C-terminal domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709545" 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 members of a 2-generation Asian family (family B) with CMYO1A, <a href="#68" class="mim-tip-reference" title="Quinlivan, R. M., Muller, C. R., Davis, M., Laing, N. G., Evans, G. A., Dwyer, J., Dove, J., Roberts, A. P., Sewry, C. A. <strong>Central core disease: clinical, pathological, and genetic features.</strong> Arch. Dis. Child. 88: 1051-1055, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14670767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14670767</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14670767[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/adc.88.12.1051" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14670767">Quinlivan et al. (2003)</a> identified a heterozygous R4893W mutation in the RYR1 gene. The mutation occurred in region 3 in the C terminus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14670767" 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="0045" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0045 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
RYR1, TYR4864CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs118192146 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118192146;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=rs118192146" 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=rs118192146" 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=RCV000056251 OR RCV000119535" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056251, RCV000119535" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056251...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 affected individuals from a 2-generation family (family C) with autosomal dominant congenital myopathy-1A (CMYO1A; <a href="/entry/117000">117000</a>), <a href="#68" class="mim-tip-reference" title="Quinlivan, R. M., Muller, C. R., Davis, M., Laing, N. G., Evans, G. A., Dwyer, J., Dove, J., Roberts, A. P., Sewry, C. A. <strong>Central core disease: clinical, pathological, and genetic features.</strong> Arch. Dis. Child. 88: 1051-1055, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14670767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14670767</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14670767[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/adc.88.12.1051" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14670767">Quinlivan et al. (2003)</a> identified a heterozygous mutation in the RYR1 gene, resulting in a tyr4864-to-cys (R4864C) substitution in exon 102. The mutation occurred in region 3 in the C terminus. Of note, a 44-year-old male family member who carried the mutation was unaffected, suggesting incomplete penetrance, although he had a son with a congenital foot deformity who was not studied. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14670767" 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="seeAlso" class="mim-anchor"></a>
|
|
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<a href="#Fagerlund1996" class="mim-tip-reference" title="Fagerlund, T., Ording, H., Bendixen, D., Islander, G., Ranklev-Twetman, E., Berg, K. <strong>RYR1 mutation G1021A (gly341-to-arg) is not frequent in Danish and Swedish families with malignant hyperthermia susceptibility.</strong> Clin. Genet. 49: 186-188, 1996.">Fagerlund et al. (1996)</a>; <a href="#Fagerlund1992" class="mim-tip-reference" title="Fagerlund, T., Islander, G., Ranklev, E., Harbitz, I., Hauge, J. G., Mokleby, E., Berg, K. <strong>Genetic recombination between malignant hyperthermia and calcium release channel in skeletal muscle.</strong> Clin. Genet. 41: 270-272, 1992.">Fagerlund et al. (1992)</a>; <a href="#Levitt1991" class="mim-tip-reference" title="Levitt, R. C., Nouri, N., Jedlicka, A. E., McKusick, V. A., Marks, A. R., Shutack, J. G., Fletcher, J. E., Rosenberg, H., Meyers, D. A. <strong>Evidence for genetic heterogeneity in malignant hyperthermia susceptibility.</strong> Genomics 11: 543-547, 1991.">Levitt et al.
|
|
(1991)</a>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</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="Adeokun1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Adeokun, A. M., West, S. P., Ellis, F. R., Halsall, P. J., Hopkins, P. M., Foroughmand, A. M., Iles, D. E., Robinson, R. L., Stewart, A. D., Curran, J. L.
|
|
<strong>The G1021A substitution in the RYR1 gene does not cosegregate with malignant hyperthermia susceptibility in a British pedigree.</strong>
|
|
Am. J. Hum. Genet. 60: 833-341, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9106529/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9106529</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9106529" 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="2" class="mim-anchor"></a>
|
|
<a id="Alestrom1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Alestrom, A., Fagerlund, T. H., Berg, K.
|
|
<strong>A simple method to detect the RYR1 mutation G1021A, a cause of malignant hyperthermia susceptibility.</strong>
|
|
Clin. Genet. 47: 274-275, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7554356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7554356</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7554356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1995.tb04311.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Avila2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Avila, G., O'Brien, J. J., Dirksen, R. T.
|
|
<strong>Excitation-contraction uncoupling by a human central core disease mutation in the ryanodine receptor.</strong>
|
|
Proc. Nat. Acad. Sci. 98: 4215-4220, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11274444/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11274444</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11274444[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=11274444" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.071048198" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Barone1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Barone, V., Bertocchini, F., Bottinelli, R., Protasi, F., Allen, P. D., Armstrong, C. F., Reggiani, C., Sorrentino, V.
|
|
<strong>Contractile impairment and structural alterations of skeletal muscles from knockout mice lacking type 1 and type 3 ryanodine receptors.</strong>
|
|
FEBS Lett. 422: 160-164, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9489997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9489997</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9489997" 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/s0014-5793(98)00003-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Bellinger2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bellinger, A. M., Reiken, S., Carlson, C., Mongillo, M., Liu, X., Rothman, L., Matecki, S., Lacampagne, A., Marks, A. R.
|
|
<strong>Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle.</strong>
|
|
Nature Med. 15: 325-330, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19198614/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19198614</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19198614[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=19198614" 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/nm.1916" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Benkusky2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Benkusky, N. A., Farrell, E. F., Valdivia, H. H.
|
|
<strong>Ryanodine receptor channelopathies.</strong>
|
|
Biochem. Biophys. Res. Commun. 322: 1280-1285, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15336975/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15336975</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15336975" 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.bbrc.2004.08.033" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Brandt1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brandt, A., Schleithoff, L., Jurkat-Rott, K., Klingler, W., Baur, C., Lehmann-Horn, F.
|
|
<strong>Screening of ryanodine receptor gene in 105 malignant hyperthermia families: novel mutations and concordance with the in vitro contracture test.</strong>
|
|
Hum. Molec. Genet. 8: 2055-2062, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10484775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10484775</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10484775" 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/8.11.2055" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Brennan2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brennan, S., Garcia-Castaneda, M., Michelucci, A., Sabha, N., Malik, S., Groom, L., LaPierre, L. W., Dowling, J. J., Dirksen, R. T.
|
|
<strong>Mouse model of severe recessive RYR1-related myopathy.</strong>
|
|
Hum. Molec. Genet. 28: 3024-3036, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31107960/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31107960</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31107960[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=31107960" 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/ddz105" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Brown2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brown, R. L., Pollock, A. N., Couchman, K. G., Hodges, M., Hutchinson, D. O., Waaka, R., Lynch, P., McCarthy, T. V., Stowell, K. M.
|
|
<strong>A novel ryanodine receptor mutation and genotype-phenotype correlation in a large malignant hyperthermia New Zealand Maori pedigree.</strong>
|
|
Hum. Molec. Genet. 9: 1515-1524, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10888602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10888602</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10888602" 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/9.10.1515" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Cavanna1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cavanna, J. S., Greenfield, A. J., Johnson, K. J., Marks, A. R., Nadal-Ginard, B., Brown, S. D. M.
|
|
<strong>Establishment of the mouse chromosome 7 region with homology to the myotonic dystrophy region of human chromosome 19q.</strong>
|
|
Genomics 7: 12-18, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1970795/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1970795</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1970795" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(90)90513-t" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Chelu2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chelu, M. G., Goonasekera, S. A., Durham, W. J., Tang, W., Lueck, J. D., Riehl, J., Pessah, I. N., Zhang, P., Bhattacharjee, M. B., Dirksen, R. T., Hamilton, S. L.
|
|
<strong>Heat- and anesthesia-induced malignant hyperthermia in an RyR1 knock-in mouse.</strong>
|
|
FASEB J. 20: 329-330, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16284304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16284304</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16284304" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1096/fj.05-4497fje" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Cheng1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cheng, H., Lederer, W. J., Cannell, M. B.
|
|
<strong>Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle.</strong>
|
|
Science 262: 740-744, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8235594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8235594</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8235594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.8235594" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="D'Arcy2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
D'Arcy, C. E., Bjorksten, A., Yiu, E. M., Bankier, A., Gillies, R., McLean, C. A., Shield, L. K., Ryan, M. M.
|
|
<strong>King-Denborough syndrome caused by a novel mutation in the ryanodine receptor gene.</strong>
|
|
Neurology 71: 776-777, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18765655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18765655</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18765655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000324929.33780.2f" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Deufel1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Deufel, T., Sudbrak, R., Feist, Y., Rubsam, B., Du Chesne, I., Schafer, K.-L., Roewer, N., Grimm, T., Lehmann-Horn, F., Hartung, E. J., Muller, C. R.
|
|
<strong>Discordance, in a malignant hyperthermia pedigree, between in vitro contracture-test phenotypes and haplotypes for the MHS1 region on chromosome 19q12-13.2, comprising the C1840T transition in the RYR1 gene.</strong>
|
|
Am. J. Hum. Genet. 56: 1334-1342, 1995. Note: Erratum: Am. J. Hum. Genet. 57: 520 only, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7762556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7762556</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7762556" 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="15" class="mim-anchor"></a>
|
|
<a id="Dowling2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dowling, J. J., Lillis S., Amburgey, K., Zhou, H., Al-Sarraj, S., Buk, S. J. A., Wraige, E., Chow, G., Abbs, S., Leber, S., Lachlan, K., Baralle, D., Taylor, A., Sewry, C., Muntoni, F., Jungbluth, H.
|
|
<strong>King-Denborough syndrome with and without mutations in the skeletal muscle ryanodine receptor (RYR1) gene.</strong>
|
|
Neuromusc. Disord. 21: 420-427, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21514828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21514828</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21514828" 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.2011.03.006" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Ducreux2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ducreux, S., Zorzato, F., Muller, C., Sewry, C., Muntoni, F., Quinlivan, R., Restagno, G., Girard, T., Treves, S.
|
|
<strong>Effect of ryanodine receptor mutations on interleukin-6 release and intracellular calcium homeostasis in human myotubes from malignant hyperthermia-susceptible individuals and patients affected by central core disease.</strong>
|
|
J. Biol. Chem. 279: 43838-43846, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15299003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15299003</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15299003" 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.M403612200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Durham2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Durham, W. J., Aracena-Parks, P., Long, C., Rossi, A. E., Goonasekera, S. A., Boncompagni, S., Galvan, D. L., Gilman, C. P., Baker, M. R., Shirokova, N., Protasi, F., Dirksen, R., Hamilton, S. L.
|
|
<strong>RyR1 S-nitrosylation underlies environmental heat stroke and sudden death in Y522S RyR1 knockin mice.</strong>
|
|
Cell 133: 53-65, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18394989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18394989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18394989[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=18394989" 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.cell.2008.02.042" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Efremov2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Efremov, R. G., Leitner, A., Aebersold, R., Raunser, S.
|
|
<strong>Architecture and conformational switch mechanism of the ryanodine receptor.</strong>
|
|
Nature 517: 39-43, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25470059/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25470059</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25470059" 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/nature13916" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Elbaz2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Elbaz, M., Ruiz, A., Bachmann, C., Eckhardt, J., Pelczar, P., Venturi, E., Lindsay, C., Wilson, A. D., Alhussni, A., Humberstone, T., Pietrangelo, L., Boncompagni, S., Sitsapesan, R., Treves, S., Zorzato, F.
|
|
<strong>Quantitative RyR1 reduction and loss of calcium sensitivity of RyR1Q1970fsX16+A4329D cause cores and loss of muscle strength.</strong>
|
|
Hum. Molec. Genet. 28: 2987-2999, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31044239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31044239</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31044239" 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/ddz092" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Elbaz2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Elbaz, M., Ruiz, A., Eckhardt, J., Pelczar, O., Muntoni, F. Boncompagni, S., Treves, S., Zorzato, F.
|
|
<strong>Quantitative reduction of RyR1 protein caused by a single-allele frameshift mutation in RYR1 ex36 impairs the strength of adult skeletal muscle fibres.</strong>
|
|
Hum. Molec. Genet. 28: 1872-1884, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30689883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30689883</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30689883" 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/ddz025" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Eu2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eu, J. P., Sun, J., Xu, L., Stamler, J. S., Meissner, G.
|
|
<strong>The skeletal muscle calcium release channel: coupled O2 sensor and NO signaling functions.</strong>
|
|
Cell 102: 499-509, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10966111/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10966111</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10966111" 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/s0092-8674(00)00054-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Fagerlund1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fagerlund, T. H., Islander, G., Ranklev-Twetman, E., Berg, K.
|
|
<strong>Recombination between the postulated CCD/MHE/MHS locus and RYR1 gene markers.</strong>
|
|
Clin. Genet. 50: 455-458, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9147872/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9147872</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9147872" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1996.tb02711.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Fagerlund1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fagerlund, T. H., Islander, G., Twetman, E. R., Berg, K.
|
|
<strong>A search for three known RYR1 gene mutations in 41 Swedish families with predisposition to malignant hyperthermia.</strong>
|
|
Clin. Genet. 48: 12-16, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7586638/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7586638</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7586638" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1995.tb04047.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Fagerlund1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fagerlund, T. H., Ording, H., Bendixen, D., Islander, G., Ranklev Twetman, E., Berg, K.
|
|
<strong>Discordance between malignant hyperthermia susceptibility and RYR1 mutation C1840T in two Scandinavian MH families exhibiting this mutation.</strong>
|
|
Clin. Genet. 52: 416-421, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9520251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9520251</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9520251" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1997.tb02561.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Fagerlund1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fagerlund, T., Islander, G., Ranklev, E., Harbitz, I., Hauge, J. G., Mokleby, E., Berg, K.
|
|
<strong>Genetic recombination between malignant hyperthermia and calcium release channel in skeletal muscle.</strong>
|
|
Clin. Genet. 41: 270-272, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1318804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1318804</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1318804" 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="26" class="mim-anchor"></a>
|
|
<a id="Fagerlund1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fagerlund, T., Ording, H., Bendixen, D., Berg, K.
|
|
<strong>Search for three known mutations in the RYR gene in 48 Danish families with malignant hyperthermia.</strong>
|
|
Clin. Genet. 46: 401-404, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7889656/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7889656</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7889656" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1994.tb04406.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Fagerlund1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fagerlund, T., Ording, H., Bendixen, D., Islander, G., Ranklev-Twetman, E., Berg, K.
|
|
<strong>RYR1 mutation G1021A (gly341-to-arg) is not frequent in Danish and Swedish families with malignant hyperthermia susceptibility.</strong>
|
|
Clin. Genet. 49: 186-188, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8828983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8828983</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8828983" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1996.tb03284.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Ferreiro2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ferreiro, A., Monnier, N., Romero, N. B., Leroy, J.-P., Bonnemann, C., Haenggeli, C.-A., Straub, V., Voss, W. D., Nivoche, Y., Jungbluth, H., Lemainque, A., Voit, T., Lunardi, J., Fardeau, M., Guicheney, P.
|
|
<strong>A recessive form of central core disease, transiently presenting as multi-minicore disease, is associated with a homozygous mutation in the ryanodine receptor type 1 gene.</strong>
|
|
Ann. Neurol. 51: 750-759, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12112081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12112081</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12112081" 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.10231" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Fujii1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fujii, J., Otsu, K., Zorzato, F., de Leon, S., Khanna, V. K., Weiler, J. E., O'Brien, P. J., MacLennan, D. H.
|
|
<strong>Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia.</strong>
|
|
Science 253: 448-451, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1862346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1862346</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1862346" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1862346" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Gillard1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gillard, E. F., Otsu, K., Fujii, J., Duff, C., de Leon, S., Khanna, V. K., Britt, B. A., Worton, R. G., MacLennan, D. H.
|
|
<strong>Polymorphisms and deduced amino acid substitutions in the coding sequence of the ryanodine receptor (RYR1) gene in individuals with malignant hyperthermia.</strong>
|
|
Genomics 13: 1247-1254, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1354642/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1354642</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1354642" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(92)90042-q" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Gillard1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gillard, E. F., Otsu, K., Fujii, J., Khanna, V. K., de Leon, S., Derdemezi, J., Britt, B. A., Duff, C. L., Worton, R. G., MacLennan, D. H.
|
|
<strong>A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia.</strong>
|
|
Genomics 11: 751-755, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1774074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1774074</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1774074" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(91)90084-r" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Girard2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Girard, T., Urwyler, A., Censier, K., Mueller, C. R., Zorzato, F., Treves, S.
|
|
<strong>Genotype-phenotype comparison of the Swiss malignant hyperthermia population.</strong>
|
|
Hum. Mutat. 18: 357-358, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11668625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11668625</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11668625" 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/humu.1203" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Guis2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guis, S., Figarella-Branger, D., Monnier, N., Bendahan, D., Kozak-Ribbens, G., Mattei, J.-P., Lunardi, J., Cozzone, P. J., Pellissier, J.-F.
|
|
<strong>Multiminicore disease in a family susceptible to malignant hyperthermia: histology, in vitro contracture tests, and genetic characterization.</strong>
|
|
Arch. Neurol. 61: 106-113, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14732627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14732627</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14732627" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archneur.61.1.106" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Hall-Curran1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hall-Curran, J. L., Stewart, A. D., Ball, S. P., Halsall, J. P., Hopkins, P. M., Ellis, F. R.
|
|
<strong>No C1840 to T mutation in RYR1 in malignant hyperthermia. (Letter)</strong>
|
|
Hum. Mutat. 2: 330, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8401544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8401544</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8401544" 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/humu.1380020418" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Harbitz1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Harbitz, I., Chowdhary, B., Thomsen, P. D., Davies, W., Kaufmann, U., Kran, S., Gustavsson, I., Christensen, K., Hauge, J. G.
|
|
<strong>Assignment of the porcine calcium release channel gene, a candidate for the malignant hyperthermia locus, to the 6p11-q21 segment of chromosome 6.</strong>
|
|
Genomics 8: 243-248, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2174405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2174405</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2174405" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(90)90278-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Harbitz1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Harbitz, I., Kristensen, T., Bosnes, M., Kran, S., Davies, W.
|
|
<strong>DNA sequence of the skeletal muscle calcium release channel cDNA and verification of the arg615-to-cys615 mutation, associated with porcine malignant hyperthermia, in Norwegian Landrace pigs.</strong>
|
|
Animal Genet. 23: 395-402, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1329581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1329581</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1329581" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2052.1992.tb02157.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Johnston2021" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johnston, J. J., Dirksen, R. T., Girard, T., Gonsalves, S. G., Hopkins, P. M., Riazi, S., Saddic, L. A., Sambuughin, N., Saxena, R., Stowell, K., Weber, J., Rosenberg, H., Biesecker, L. G.
|
|
<strong>Variant curation expert panel recommendations for RYR1 pathogenicity classifications in malignant hyperthermia susceptibility.</strong>
|
|
Genet. Med. 23: 1288-1295, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33767344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33767344</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33767344[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=33767344" 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/s41436-021-01125-w" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Joseph2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Joseph, M. R., Theroux, M. C., Mooney, J. J., Falitz, S., Brandom, B. W., Byler, D. L.
|
|
<strong>Intraoperative presentation of malignant hyperthermia (confirmed by RYR1 gene mutation, c.7522C-T; p.R2508C) leads to diagnosis of King-Denborough syndrome in a child with hypotonia and dysmorphic features: a case report.</strong>
|
|
A. A. Case Rep. 8: 55-57, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27918309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27918309</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27918309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1213/XAA.0000000000000421" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Jungbluth2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jungbluth, H., Muller, C. R., Halliger-Keller, B., Brockington, M., Brown, S. C., Feng, L., Chattopadhyay, A., Mercuri, E., Manzur, A. Y., Ferreiro, A., Laing, N. G., Davis, M. R., Roper, H. P., Dubowitz, V., Bydder, G., Sewry, C. A., Muntoni, F.
|
|
<strong>Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores.</strong>
|
|
Neurology 59: 284-287, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12136074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12136074</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12136074" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.59.2.284" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Jungbluth2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jungbluth, H., Zhou, H., Hartley, L., Halliger-Keller, B., Messina, S., Longman, C., Brockington, M., Robb, S. A., Straub, V., Voit, T., Swash, M., Ferreiro, A., Bydder, G., Sewry, C. A., Muller, C., Muntoni, F.
|
|
<strong>Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.</strong>
|
|
Neurology 65: 1930-1935, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16380615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16380615</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16380615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000188870.37076.f2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Keating1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Keating, K. E., Quane, K. A., Manning, B. M., Lehane, M., Hartung, E., Censier, K., Urwyler, A., Klausnitzer, M., Muller, C. R., Heffron, J. J. A., McCarthy, T. V.
|
|
<strong>Detection of a novel RYR1 mutation in four malignant hyperthermia pedigrees.</strong>
|
|
Hum. Molec. Genet. 3: 1855-1858, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7849712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7849712</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7849712" 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/3.10.1855" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Klein2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Klein, A., Lillis, S., Munteanu, I., Scoto, M., Zhou, H., Quinlivan, R., Straub, V., Manzur, A. Y., Roper, H., Jeannet, P-Y., Rakowicz, W., Jones, D. H., and 20 others.
|
|
<strong>Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.</strong>
|
|
Hum. Mutat. 33: 981-988, 2012. Note: Erratum: Hum. Mutat. 33: 1310, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22473935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22473935</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22473935" 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/humu.22056" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Kossugue2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kossugue, P. M., Paim, J. F., Navarro, M. M., Silva, H. C., Pavanello, R. C. M., Gurgel-Giannetti, J., Zatz, M., Vainzof, M.
|
|
<strong>Central core disease due to recessive mutations in RYR1 gene: is it more common than described?</strong>
|
|
Muscle Nerve 35: 670-674, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17226826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17226826</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17226826" 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.20715" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Levitt1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Levitt, R. C., Nouri, N., Jedlicka, A. E., McKusick, V. A., Marks, A. R., Shutack, J. G., Fletcher, J. E., Rosenberg, H., Meyers, D. A.
|
|
<strong>Evidence for genetic heterogeneity in malignant hyperthermia susceptibility.</strong>
|
|
Genomics 11: 543-547, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1774061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1774061</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1774061" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(91)90061-i" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Lyfenko2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lyfenko, A. D., Goonasekera, S. A., Dirksen, R. T.
|
|
<strong>Dynamic alterations in myoplasmic Ca(2+) in malignant hyperthermia and central core disease.</strong>
|
|
Biochem. Biophys. Res. Commun. 322: 1256-1266, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15336973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15336973</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15336973" 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.bbrc.2004.08.031" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Lynch1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lynch, P. J., Tong, J., Lehane, M., Mallet, A., Giblin, L., Heffron, J. J. A., Vaughan, P., Zafra, G., MacLennan, D. H., McCarthy, T. V.
|
|
<strong>A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca(2+) release channel function and severe central core disease.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 4164-4169, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10097181/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10097181</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10097181[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=10097181" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.96.7.4164" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="MacKenzie1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
MacKenzie, A. E., Korneluk, R. G., Zorzato, F., Fujii, J., Phillips, M., Iles, D., Wieringa, B., Leblond, S., Bailly, J., Willard, H. F., Duff, C., Worton, R. G., MacLennan, D. H.
|
|
<strong>The human ryanodine receptor gene: its mapping to 19q13.1, placement in a chromosome 19 linkage group, and exclusion as the gene causing myotonic dystrophy.</strong>
|
|
Am. J. Hum. Genet. 46: 1082-1089, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1971150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1971150</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1971150" 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="48" class="mim-anchor"></a>
|
|
<a id="MacLennan1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
MacLennan, D. H., Zorzato, F., Fujii, J., Otsu, K., Phillips, M., Lai, F. A., Meissner, G., Green, N. M., Willard, H. F., Britt, B. A., Worton, R. G., Korneluk, R. G.
|
|
<strong>Cloning and localization of the human calcium release channel (ryanodine receptor) gene to the proximal long arm (cen-q13.2) of human chromosome 19. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 45 (suppl.): A205 only, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Manning1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Manning, B. M., Quane, K. A., Lynch, P. J., Urwyler, A., Tegazzin, V., Krivosic-Horber, R., Censier, K., Comi, G., Adnet, P., Wolz, W., Lunardi, J., Muller, C. R., McCarthy, T. V.
|
|
<strong>Novel mutations at a CpG dinucleotide in the ryanodine receptor in malignant hyperthermia.</strong>
|
|
Hum. Mutat. 11: 45-50, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9450902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9450902</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9450902" 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)1098-1004(1998)11:1<45::AID-HUMU7>3.0.CO;2-K" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="50" class="mim-anchor"></a>
|
|
<a id="Manning1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Manning, B. M., Quane, K. A., Ording, H., Urwyler, A., Tegazzin, V., Lehane, M., O'Halloran, J., Hartung, E., Giblin, L. M., Lynch, P. J., Vaughan, P., Censier, K., Bendixen, D., Comi, G., Heytens, L., Monsieurs, K., Fagerlund, T., Wolz, W., Heffron, J. J. A., Muller, C. R., McCarthy, T. V.
|
|
<strong>Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation.</strong>
|
|
Am. J. Hum. Genet. 62: 599-609, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9497245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9497245</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9497245" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/301748" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Mattei1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mattei, M. G., Giannini, G., Moscatelli, F., Sorrentino, V.
|
|
<strong>Chromosomal localization of murine ryanodine receptor genes RYR1, RYR2, and RYR3 by in situ hybridization.</strong>
|
|
Genomics 22: 202-204, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7959768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7959768</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7959768" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1994.1362" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="McCarthy2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McCarthy, T. V., Quane, K. A., Lynch, P. J.
|
|
<strong>Ryanodine receptor mutations in malignant hyperthermia and central core disease.</strong>
|
|
Hum. Mutat. 15: 410-417, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10790202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10790202</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10790202" 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)1098-1004(200005)15:5<410::AID-HUMU2>3.0.CO;2-D" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="McKie2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McKie, A. B., Alsaedi, A., Vogt, J., Stuurman, K. E., Weiss, M. M., Shakeel, H., Tee, L., Morgan, N. V., Nikkels, P. G. J., van Haaften, G., Park, S.-M., van der Smagt, J. J., Bugiani, M., Maher, E. R.
|
|
<strong>Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome.</strong>
|
|
Acta Neuropath. Commun. 2: 148, 2014. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25476234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25476234</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25476234[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=25476234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1186/s40478-014-0148-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Monnier2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Monnier, N., Ferreiro, A., Marty, I., Labarre-Vila, A., Mezin, P., Lunardi, J.
|
|
<strong>A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia.</strong>
|
|
Hum. Molec. Genet. 12: 1171-1178, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12719381/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12719381</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12719381" 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/ddg121" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Monnier2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Monnier, N., Kozak-Ribbens, G., Krivosic-Horber, R., Nivoche, Y., Qi, D., Kraev, N., Loke, J., Sharma, P., Tegazzin, V., Figarella-Branger, D., Romero, N., Mezin, P., Bendahan, D., Payen, J.-F., Depret, T., Maclennan, D. H., Lunardi, J.
|
|
<strong>Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility.</strong>
|
|
Hum. Mutat. 26: 413-425, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16163667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16163667</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16163667" 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/humu.20231" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="56" class="mim-anchor"></a>
|
|
<a id="Monnier2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Monnier, N., Marty, I., Faure, J., Castiglioni, C., Desnuelle, C., Sacconi, S., Estournet, B., Ferreiro, A., Romero, N., Laquerriere, A., Lazaro, L., Martin, J.-J., Morava, E., Rossi, A., Van der Kooi, A., de Visser, M., Verschuuren, C., Lunardi, J.
|
|
<strong>Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.</strong>
|
|
Hum. Mutat. 29: 670-678, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18253926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18253926</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18253926" 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/humu.20696" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="57" class="mim-anchor"></a>
|
|
<a id="Monnier2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Monnier, N., Romero, N. B., Lerale, J., Landrieu, P., Nivoche, Y., Fardeau, M., Lunardi, J.
|
|
<strong>Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor.</strong>
|
|
Hum. Molec. Genet. 10: 2581-2592, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709545/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709545</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709545" 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/10.22.2581" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="58" class="mim-anchor"></a>
|
|
<a id="Monnier2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Monnier, N., Romero, N. B., Lerale, J., Nivoche, Y., Qi, D., MacLennan, D. H., Fardeau, M., Lunardi, J.
|
|
<strong>An autosomal dominant congenital myopathy with cores and rods is associated with a neomutation in the RYR1 gene encoding the skeletal muscle ryanodine receptor.</strong>
|
|
Hum. Molec. Genet. 9: 2599-2608, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11063719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11063719</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11063719" 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/9.18.2599" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="59" class="mim-anchor"></a>
|
|
<a id="Monsieurs1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Monsieurs, K. G., Van Broeckhoven, C., Martin, J.-J., Van Hoof, V. O., Heytens, L.
|
|
<strong>Gly341arg mutation indicating malignant hyperthermia susceptibility: specific cause of chronically elevated serum creatine kinase activity.</strong>
|
|
J. Neurol. Sci. 154: 62-65, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9543323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9543323</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9543323" 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/s0022-510x(97)00215-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="60" class="mim-anchor"></a>
|
|
<a id="O'Brien1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
O'Brien, R. O., Taske, N. L., Hansbro, P. M., Matthaei, K. I., Hogan, S. P., Denborough, M. A., Foster, P. S.
|
|
<strong>Exclusion of defects in the skeletal muscle specific regions of the DHPR alpha-1 subunit as frequent causes of malignant hyperthermia.</strong>
|
|
J. Med. Genet. 32: 913-914, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8592342/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8592342</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8592342" 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.32.11.913" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="61" class="mim-anchor"></a>
|
|
<a id="Otsu1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Otsu, K., Khanna, V. K., Archibald, A. L., MacLennan, D. H.
|
|
<strong>Cosegregation of porcine malignant hyperthermia and a probable causal mutation in the skeletal muscle ryanodine receptor gene in backcross families.</strong>
|
|
Genomics 11: 744-750, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1774073/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1774073</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1774073" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(91)90083-q" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="62" class="mim-anchor"></a>
|
|
<a id="Otsu1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Otsu, K., Nishida, K., Kimura, Y., Kuzuya, T., Hori, M., Kamada, T., Tada, M.
|
|
<strong>The point mutation arg615-to-cys in the Ca(2+) release channel of skeletal sarcoplasmic reticulum is responsible for hypersensitivity to caffeine and halothane in malignant hyperthermia.</strong>
|
|
J. Biol. Chem. 269: 9413-9415, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7511586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7511586</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7511586" 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="63" class="mim-anchor"></a>
|
|
<a id="Otsu1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Otsu, K., Phillips, M. S., Khanna, V. K., de Leon, S., MacLennan, D. H.
|
|
<strong>Refinement of diagnostic assays for a probable causal mutation for porcine and human malignant hyperthermia.</strong>
|
|
Genomics 13: 835-837, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1639409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1639409</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1639409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(92)90163-m" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="64" class="mim-anchor"></a>
|
|
<a id="Phillips1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Phillips, M. S., Fujii, J., Khanna, V. K., DeLeon, S., Yokobata, K., De Jong, P. J., MacLennan, D. H.
|
|
<strong>The structural organization of the human skeletal muscle ryanodine receptor (RYR1) gene.</strong>
|
|
Genomics 34: 24-41, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8661021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8661021</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8661021" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1996.0238" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="65" class="mim-anchor"></a>
|
|
<a id="Quane1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Quane, K. A., Healy, J. M. S., Keating, K. E., Manning, B. M., Couch, F. J., Palmucci, L. M., Doriguzzi, C., Fagerlund, T. H., Berg, K., Ording, H., Bendixen, D., Mortier, W., Linz, U., Muller, C. R., McCarthy, T. V.
|
|
<strong>Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia.</strong>
|
|
Nature Genet. 5: 51-55, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8220423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8220423</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8220423" 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/ng0993-51" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="66" class="mim-anchor"></a>
|
|
<a id="Quane1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Quane, K. A., Keating, K. E., Healy, J. M. S., Manning, B. M., Krivosic-Horber, R., Krivosic, I., Monnier, N., Lunardi, J., McCarthy, T. V.
|
|
<strong>Mutation screening of the RYR1 gene in malignant hyperthermia: detection of a novel tyr to ser mutation in a pedigree with associated central cores.</strong>
|
|
Genomics 23: 236-239, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7829078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7829078</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7829078" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1994.1483" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="67" class="mim-anchor"></a>
|
|
<a id="Quane1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Quane, K. A., Keating, K. E., Manning, B. M., Healy, J. M. S., Monsieurs, K., Heffron, J. J. A., Lehane, M., Heytens, L., Krivosic-Horber, R., Adnet, P., Ellis, F. R., Monnier, N., Lunardi, J., McCarthy, T. V.
|
|
<strong>Detection of a novel common mutation in the ryanodine receptor gene in malignant hyperthermia: implications for diagnosis and heterogeneity studies.</strong>
|
|
Hum. Molec. Genet. 3: 471-476, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8012359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8012359</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8012359" 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/3.3.471" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="68" class="mim-anchor"></a>
|
|
<a id="Quinlivan2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Quinlivan, R. M., Muller, C. R., Davis, M., Laing, N. G., Evans, G. A., Dwyer, J., Dove, J., Roberts, A. P., Sewry, C. A.
|
|
<strong>Central core disease: clinical, pathological, and genetic features.</strong>
|
|
Arch. Dis. Child. 88: 1051-1055, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14670767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14670767</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14670767[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=14670767" 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/adc.88.12.1051" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="69" class="mim-anchor"></a>
|
|
<a id="Richter1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Richter, M., Schleithoff, L., Deufel, T., Lehmann-Horn, F., Herrmann-Frank, A.
|
|
<strong>Functional characterization of a distinct ryanodine receptor mutation in human malignant hyperthermia-susceptible muscle.</strong>
|
|
J. Biol. Chem. 272: 5256-5260, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9030597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9030597</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9030597" 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.272.8.5256" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="70" class="mim-anchor"></a>
|
|
<a id="Robinson2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Robinson, R., Carpenter, D., Shaw, M.-A., Halsall, J., Hopkins, P.
|
|
<strong>Mutations in RYR1 in malignant hyperthermia and central core disease.</strong>
|
|
Hum. Mutat. 27: 977-989, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16917943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16917943</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16917943" 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/humu.20356" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="71" class="mim-anchor"></a>
|
|
<a id="Robinson2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Robinson, R. L., Brooks, C., Brown, S. L., Ellis, F. R., Halsall, P. J., Quinnell, R. J., Shaw, M.-A., Hopkins, P. M.
|
|
<strong>RYR1 mutations causing central core disease are associated with more severe malignant hyperthermia in vitro contracture test phenotypes.</strong>
|
|
Hum. Mutat. 20: 88-97, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12124989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12124989</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12124989" 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/humu.10098" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="72" class="mim-anchor"></a>
|
|
<a id="Sambuughin2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sambuughin, N., McWilliams, S., de Bantel, A., Sivakumar, K., Nelson, T. E.
|
|
<strong>Single-amino-acid deletion in the RYR1 gene, associated with malignant hyperthermia susceptibility and unusual contraction phenotype.</strong>
|
|
Am. J. Hum. Genet. 69: 204-208, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11389482/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11389482</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11389482[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=11389482" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/321270" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="73" class="mim-anchor"></a>
|
|
<a id="Sato2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sato, I., Wu, S., Ibarra, M. C. A., Hayashi, Y. K., Fujita, H., Tojo, M., Oh, S. J., Nonaka, I., Noguchi, S., Nishino, I.
|
|
<strong>Congenital neuromuscular disease with uniform type 1 fiber and RYR1 mutation.</strong>
|
|
Neurology 70: 114-122, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17538032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17538032</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17538032" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000269792.63927.86" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="74" class="mim-anchor"></a>
|
|
<a id="Scacheri2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scacheri, P. C., Hoffman, E. P., Fratkin, J. D., Semino-Mora, C., Senchak, A., Davis, M. R., Laing, N. G., Vedanarayanan, V., Subramony, S. H.
|
|
<strong>A novel ryanodine receptor gene mutation causing both cores and rods in congenital myopathy.</strong>
|
|
Neurology 55: 1689-1696, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11113224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11113224</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11113224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/wnl.55.11.1689" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="75" class="mim-anchor"></a>
|
|
<a id="Shuaib1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shuaib, A., Paasuke, R. T., Brownell, K. W.
|
|
<strong>Central core disease: clinical features in 13 patients.</strong>
|
|
Medicine 66: 389-396, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3626847/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3626847</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3626847" 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="76" class="mim-anchor"></a>
|
|
<a id="Stewart1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stewart, S. L., Rosenberg, H., Fletcher, J. E.
|
|
<strong>Failure to identify the ryanodine receptor G1021A mutation in a large North American population with malignant hyperthermia.</strong>
|
|
Clin. Genet. 54: 358-361, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9831351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9831351</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9831351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1034/j.1399-0004.1998.5440417.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="77" class="mim-anchor"></a>
|
|
<a id="Swash1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Swash, M., Schwartz, M. S.
|
|
<strong>Familial multicore disease with focal loss of cross-striations and ophthalmoplegia.</strong>
|
|
J. Neurol. Sci. 52: 1-10, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7299413/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7299413</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7299413" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0022-510x(81)90129-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="78" class="mim-anchor"></a>
|
|
<a id="Takeshima1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Takeshima, H., Iino, M., Takekura, H., Nishi, M., Kuno, J., Minowa, O., Takano, H., Noda, T.
|
|
<strong>Excitation-contraction uncoupling and muscular degeneration in mice lacking functional skeletal muscle ryanodine-receptor gene.</strong>
|
|
Nature 369: 556-559, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7515481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7515481</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7515481" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/369556a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="79" class="mim-anchor"></a>
|
|
<a id="Takeshima1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Takeshima, H., Yamazawa, T., Ikemoto, T., Takekura, H., Nishi, M., Noda, T., Iino, M.
|
|
<strong>Ca(2+)-induced Ca(2+) release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor.</strong>
|
|
EMBO J. 14: 2999-3006, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7621815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7621815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7621815" 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/j.1460-2075.1995.tb07302.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="80" class="mim-anchor"></a>
|
|
<a id="Tegazzin1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tegazzin, V., Accorsi, A., Gritti, G., Arcelli, L., Di Giovanni, A.
|
|
<strong>MH fulminant reaction after eight anaesthetics: a case report.</strong>
|
|
Minerva Anestesiol. 60: 217-219, 1994.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="81" class="mim-anchor"></a>
|
|
<a id="Tilgen2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tilgen, N., Zorzato, F., Halliger-Keller, B., Muntoni, F., Sewry, C., Palumucci, L. M., Schneider, C., Hauser, E., Lehmann-Horn, F., Muller, C. R., Treves, S.
|
|
<strong>Identification of four novel mutations in the C-terminal membrane spanning domain of the ryanodine receptor 1: association with central core disease and alteration of calcium homeostasis.</strong>
|
|
Hum. Molec. Genet. 10: 2879-2887, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741831</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11741831" 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/10.25.2879" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="82" class="mim-anchor"></a>
|
|
<a id="Tobin2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tobin, J. R., Jason, D. R., Challa, V. R., Nelson, T. E., Sambuughin, N.
|
|
<strong>Malignant hyperthermia and apparent heat stroke. (Letter)</strong>
|
|
JAMA 286: 168-169, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11448278/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11448278</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11448278" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/jama.286.2.168" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="83" class="mim-anchor"></a>
|
|
<a id="Tojo2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tojo, M., Ozawa, M., Nonaka, I.
|
|
<strong>Central core disease and congenital neuromuscular disease with uniform type 1 fibers in one family.</strong>
|
|
Brain Dev. 22: 262-264, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10838116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10838116</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10838116" 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/s0387-7604(00)00108-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="84" class="mim-anchor"></a>
|
|
<a id="Trask1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Trask, B., Fertitta, A., Christensen, M., Youngblom, J., Bergmann, A., Copeland, A., de Jong, P., Mohrenweiser, H., Olsen, A., Carrano, A., Tynan, K.
|
|
<strong>Fluorescence in situ hybridization mapping of human chromosome 19: cytogenetic band location of 540 cosmids and 70 genes or DNA markers.</strong>
|
|
Genomics 15: 133-145, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432525</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8432525" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1993.1021" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="85" class="mim-anchor"></a>
|
|
<a id="Tung2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tung, C.-C., Lobo, P. A., Kimlicka, L., Van Petegem, F.
|
|
<strong>The amino-terminal disease hotspot of ryanodine receptors forms a cytoplasmic vestibule.</strong>
|
|
Nature 468: 585-588, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21048710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21048710</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21048710" 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/nature09471" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="86" class="mim-anchor"></a>
|
|
<a id="Wang2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, S.-Q., Song, L.-S., Lakatta, E. G., Cheng, H.
|
|
<strong>Ca(2+) signalling between single L-type Ca(2+) channels and ryanodine receptors in heart cells.</strong>
|
|
Nature 410: 592-596, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11279498/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11279498</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11279498" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/35069083" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="87" class="mim-anchor"></a>
|
|
<a id="Wehner2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wehner, M., Rueffert, H., Koenig, F., Neuhaus, J., Olthoff, D.
|
|
<strong>Increased sensitivity to 4-chloro-m-cresol and caffeine in primary myotubes from malignant hyperthermia susceptible individuals carrying the ryanodine receptor 1 thr2206met (C6617T) mutation.</strong>
|
|
Clin. Genet. 62: 135-146, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12220451/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12220451</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12220451" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1034/j.1399-0004.2002.620206.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="88" class="mim-anchor"></a>
|
|
<a id="Wilmshurst2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wilmshurst, J. M., Lillis, S., Zhou, H., Pillay, K., Henderson, H., Kress, W., Muller, C. R., Ndondo, A., Cloke, V., Cullup, T., Bertini, E., Boennemann, C., and 10 others.
|
|
<strong>RYR1 mutations are a common cause of congenital myopathies with central nuclei.</strong>
|
|
Ann. Neurol. 68: 717-726, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20839240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20839240</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20839240" 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.22119" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="89" class="mim-anchor"></a>
|
|
<a id="Wu2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wu, S., Ibarra M, C. A., Malicdan, M. C. V., Murayama, K., Ichihara, Y., Kikuchi, H., Nonaka, I., Noguchi, S., Hayashi, Y. K., Nishino, I.
|
|
<strong>Central core disease is due to RYR1 mutations in more than 90% of patients.</strong>
|
|
Brain 129: 1470-1480, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16621918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16621918</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16621918" 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/awl077" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="90" class="mim-anchor"></a>
|
|
<a id="Yan2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yan, Z., Bai, X., Yan, C., Wu, J., Li, Z., Xie, T., Peng, W., Yin, C., Li, X., Scheres, S. H. W., Shi, Y., Yan, N.
|
|
<strong>Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution.</strong>
|
|
Nature 517: 50-55, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25517095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25517095</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25517095[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=25517095" 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/nature14063" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="91" class="mim-anchor"></a>
|
|
<a id="Zalk2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zalk, R., Clarke, O. B., des Georges, A., Grassucci, R. A., Reiken, S., Mancia, F., Hendrickson, W. A., Frank, J., Marks, A. R.
|
|
<strong>Structure of a mammalian ryanodine receptor.</strong>
|
|
Nature 517: 44-49, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25470061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25470061</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25470061[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=25470061" 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/nature13950" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="92" class="mim-anchor"></a>
|
|
<a id="Zhang1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhang, Y., Chen, H. S., Khanna, V. K., De Leon, S., Phillips, M. S., Schappert, K., Britt, B. A., Brownell, A. K. W., MacLennan, D. H.
|
|
<strong>A mutation in the human ryanodine receptor gene associated with central core disease.</strong>
|
|
Nature Genet. 5: 46-50, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8220422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8220422</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8220422" 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/ng0993-46" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="93" class="mim-anchor"></a>
|
|
<a id="Zhou2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhou, H., Brockington, M., Jungbluth, H., Monk, D., Stanier, P., Sewry, C. A., Moore, G. E., Muntoni, F.
|
|
<strong>Epigenetic allele silencing unveils recessive RYR1 mutations in core myopathies.</strong>
|
|
Am. J. Hum. Genet. 79: 859-868, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033962</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033962[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=17033962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/508500" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="94" class="mim-anchor"></a>
|
|
<a id="Zorzato1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zorzato, F., Fujii, J., Otsu, K., Phillips, M., Green, N. M., Lai, F. A., Meissner, G., MacLennan, D. H.
|
|
<strong>Molecular cloning of cDNA encoding human and rabbit forms of the Ca(2+) release channel (ryanodine receptor) of skeletal muscle sarcoplasmic reticulum.</strong>
|
|
J. Biol. Chem. 265: 2244-2256, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2298749/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2298749</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2298749" 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="95" class="mim-anchor"></a>
|
|
<a id="Zorzato2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zorzato, F., Yamaguchi, N., Xu, L., Meissner, G., Muller, C. R., Pouliquin, P., Muntoni, F., Sewry, C., Girard, T., Treves, S.
|
|
<strong>Clinical and functional effects of a deletion in a COOH-terminal lumenal loop of the skeletal muscle ryanodine receptor.</strong>
|
|
Hum. Molec. Genet. 12: 379-388, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12566385/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12566385</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12566385" 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/ddg032" 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 : 02/24/2023
|
|
</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">
|
|
Bao Lige - updated : 01/06/2022<br>Hilary J. Vernon - updated : 10/11/2021<br>Hilary J. Vernon - updated : 08/27/2021<br>Hilary J. Vernon - updated : 11/30/2020<br>Hilary J. Vernon - updated : 10/29/2020<br>Cassandra L. Kniffin - updated : 5/20/2015<br>Ada Hamosh - updated : 3/9/2015<br>Cassandra L. Kniffin - updated : 6/5/2013<br>Cassandra L. Kniffin - updated : 2/16/2011<br>Ada Hamosh - updated : 2/2/2011<br>Cassandra L. Kniffin - updated : 5/28/2009<br>Cassandra L. Kniffin - updated : 1/13/2009<br>Cassandra L. Kniffin - updated : 8/26/2008<br>Victor A. McKusick - updated : 10/9/2006<br>Cassandra L. Kniffin - updated : 10/4/2006<br>Cassandra L. Kniffin - updated : 6/2/2006<br>Cassandra L. Kniffin - updated : 4/6/2006<br>Victor A. McKusick - updated : 11/22/2005<br>George E. Tiller - updated : 2/25/2005<br>Patricia A. Hartz - updated : 2/18/2005<br>George E. Tiller - updated : 1/4/2005<br>Cassandra L. Kniffin - updated : 12/17/2004<br>Cassandra L. Kniffin - reorganized : 6/3/2004<br>Victor A. McKusick - updated : 11/26/2002<br>Victor A. McKusick - updated : 11/5/2002<br>Cassandra L. Kniffin - updated : 10/14/2002<br>Victor A. McKusick - updated : 9/17/2002<br>Victor A. McKusick - updated : 8/20/2002<br>George E. Tiller - updated : 8/13/2002<br>George E. Tiller - updated : 5/14/2002<br>Victor A. McKusick - updated : 8/16/2001<br>Victor A. McKusick - updated : 4/17/2001<br>Ada Hamosh - updated : 4/4/2001<br>George E. Tiller - updated : 1/24/2001<br>George E. Tiller - updated : 10/17/2000<br>Stylianos E. Antonarakis - updated : 9/5/2000<br>Ada Hamosh - updated : 7/20/2000<br>Victor A. McKusick - updated : 5/19/2000<br>Victor A. McKusick - updated : 10/25/1999<br>Victor A. McKusick - updated : 4/13/1999<br>Victor A. McKusick - updated : 1/26/1999<br>Ada Hamosh - updated : 6/12/1998<br>Victor A. McKusick - updated : 5/8/1998<br>Victor A. McKusick - updated : 3/9/1998<br>Victor A. McKusick - updated : 2/25/1998<br>Victor A. McKusick - updated : 2/2/1998<br>Victor A. McKusick - updated : 6/12/1997<br>Victor A. McKusick - updated : 3/12/1997<br>Iosif W. Lurie - updated : 7/26/1996
|
|
</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 : 11/9/1989
|
|
</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">
|
|
alopez : 07/16/2024
|
|
</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">
|
|
alopez : 02/27/2023<br>ckniffin : 02/24/2023<br>alopez : 02/21/2023<br>carol : 02/20/2023<br>carol : 02/20/2023<br>carol : 05/18/2022<br>carol : 05/16/2022<br>alopez : 02/23/2022<br>mgross : 01/06/2022<br>carol : 10/11/2021<br>carol : 09/27/2021<br>carol : 08/30/2021<br>carol : 08/27/2021<br>carol : 12/01/2020<br>carol : 11/30/2020<br>carol : 10/29/2020<br>carol : 08/30/2016<br>alopez : 05/22/2015<br>mcolton : 5/21/2015<br>ckniffin : 5/20/2015<br>alopez : 3/9/2015<br>carol : 9/17/2013<br>carol : 7/3/2013<br>tpirozzi : 7/3/2013<br>ckniffin : 6/5/2013<br>terry : 9/7/2012<br>terry : 3/11/2011<br>wwang : 3/10/2011<br>ckniffin : 2/16/2011<br>alopez : 2/7/2011<br>terry : 2/2/2011<br>wwang : 6/10/2009<br>ckniffin : 5/28/2009<br>terry : 2/3/2009<br>wwang : 1/22/2009<br>ckniffin : 1/13/2009<br>wwang : 9/19/2008<br>ckniffin : 8/26/2008<br>wwang : 5/30/2008<br>ckniffin : 4/18/2008<br>alopez : 10/10/2006<br>carol : 10/9/2006<br>carol : 10/9/2006<br>ckniffin : 10/4/2006<br>terry : 7/26/2006<br>wwang : 6/12/2006<br>ckniffin : 6/2/2006<br>carol : 4/18/2006<br>wwang : 4/12/2006<br>ckniffin : 4/6/2006<br>carol : 1/3/2006<br>wwang : 12/8/2005<br>terry : 11/22/2005<br>carol : 8/1/2005<br>carol : 3/28/2005<br>tkritzer : 3/9/2005<br>terry : 2/25/2005<br>mgross : 2/18/2005<br>mgross : 2/18/2005<br>alopez : 1/4/2005<br>tkritzer : 12/29/2004<br>ckniffin : 12/17/2004<br>carol : 6/3/2004<br>ckniffin : 6/1/2004<br>tkritzer : 3/3/2003<br>cwells : 11/26/2002<br>terry : 11/20/2002<br>carol : 11/12/2002<br>tkritzer : 11/11/2002<br>terry : 11/5/2002<br>carol : 10/21/2002<br>ckniffin : 10/14/2002<br>carol : 9/24/2002<br>tkritzer : 9/17/2002<br>tkritzer : 9/17/2002<br>tkritzer : 8/26/2002<br>tkritzer : 8/23/2002<br>terry : 8/20/2002<br>cwells : 8/13/2002<br>cwells : 5/17/2002<br>cwells : 5/14/2002<br>alopez : 10/30/2001<br>cwells : 9/7/2001<br>cwells : 8/27/2001<br>terry : 8/16/2001<br>terry : 8/16/2001<br>mcapotos : 5/9/2001<br>mcapotos : 4/25/2001<br>terry : 4/17/2001<br>alopez : 4/5/2001<br>terry : 4/4/2001<br>mcapotos : 2/1/2001<br>mcapotos : 1/24/2001<br>alopez : 10/17/2000<br>mgross : 9/5/2000<br>carol : 8/10/2000<br>mcapotos : 8/1/2000<br>mcapotos : 7/26/2000<br>mcapotos : 7/26/2000<br>terry : 7/20/2000<br>mcapotos : 6/6/2000<br>mcapotos : 6/5/2000<br>mcapotos : 5/25/2000<br>terry : 5/19/2000<br>mgross : 11/4/1999<br>mgross : 11/3/1999<br>terry : 10/25/1999<br>carol : 4/13/1999<br>terry : 4/13/1999<br>carol : 1/26/1999<br>terry : 6/17/1998<br>alopez : 6/12/1998<br>alopez : 5/15/1998<br>terry : 5/8/1998<br>alopez : 3/9/1998<br>terry : 2/25/1998<br>terry : 2/25/1998<br>mark : 2/3/1998<br>terry : 2/2/1998<br>terry : 7/7/1997<br>mark : 6/22/1997<br>mark : 6/18/1997<br>mark : 6/16/1997<br>terry : 6/12/1997<br>terry : 3/12/1997<br>terry : 3/6/1997<br>carol : 7/26/1996<br>carol : 7/15/1996<br>terry : 6/5/1996<br>terry : 6/3/1996<br>mark : 1/31/1996<br>terry : 1/24/1996<br>terry : 8/3/1995<br>mark : 6/28/1995<br>mimadm : 3/25/1995<br>carol : 9/30/1994<br>warfield : 4/21/1994<br>carol : 9/15/1993
|
|
</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> 180901
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
RYANODINE RECEPTOR 1; RYR1
|
|
|
|
</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">
|
|
RYANODINE RECEPTOR, SKELETAL MUSCLE; RYDR<br />
|
|
SKELETAL MUSCLE RYANODINE RECEPTOR; SKRR<br />
|
|
SARCOPLASMIC RETICULUM CALCIUM RELEASE CHANNEL
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: RYR1</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 764957003;
|
|
|
|
|
|
<strong>ICD10CM:</strong> G71.29;
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 19q13.2
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 19:38,433,691-38,587,564 </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="4">
|
|
<span class="mim-font">
|
|
19q13.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
{Malignant hyperthermia susceptibility 1}
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
145600
|
|
</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">
|
|
Congenital myopathy 1A, autosomal dominant, with susceptibility to malignant hyperthermia
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
117000
|
|
</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">
|
|
Congenital myopathy 1B, autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
255320
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
King-Denborough syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
619542
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</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 RYR1 gene encodes the skeletal muscle ryanodine receptor, which serves as a calcium release channel of the sarcoplasmic reticulum as well as a bridging structure connecting the sarcoplasmic reticulum and transverse tubule (MacLennan et al., 1989).</p><p>See also RYR2 (180902) and RYR3 (180903), which encode the cardiac and brain ryanodine receptors, respectively.</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>MacLennan et al. (1989) and Zorzato et al. (1990) cloned cDNAs encoding the rabbit and human ryanodine receptors. The human cDNA encodes a 5,032-amino acid protein with a molecular mass of 563.5 kD, which is made without an N-terminal sequence. Sequence analysis predicts 10 potential transmembrane sequences in the C-terminal region and 2 additional potential transmembrane sequences closer to the center of the molecule, which could form the calcium-conducting pore. The remainder of the protein is hydrophilic and presumably constitutes the cytoplasmic domain. Several potential calmodulin (see 114180)-binding sites were observed between residues 2800 and 3050. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Eu et al. (2000) reported that ambient oxygen tension (pO2) dynamically controls the redox state of 6 to 8 out of 50 thiols in each RYR1 subunit and thereby tunes the response to NO. At physiologic pO2, nanomolar NO activates the channel by S-nitrosylating a single cysteine residue. Among sarcoplasmic reticulum proteins, S-nitrosylation is specific to RYR1, and its effect on the channel is calmodulin (see 114180) dependent. Neither activation nor S-nitrosylation of the channel occurs at ambient pO2. The demonstration that channel cysteine residues subserve coupled O2 sensor and NO regulatory functions, and that these operate through the prototypic allosteric effector calmodulin, may have general implications for the regulation of redox-related systems. </p><p>Calcium-induced calcium release is a general mechanism that most cells use to amplify calcium signals. In heart cells, this mechanism is operated between voltage-gated L-type calcium channels (LCCs; see 114205) in the plasma membrane and calcium release channels, commonly known as ryanodine receptors, in the sarcoplasmic reticulum. The calcium influx through LCCs traverses a cleft of roughly 12 nm formed by the cell surface and the sarcoplasmic reticulum membrane, and activates adjacent ryanodine receptors to release calcium in the form of calcium sparks (Cheng et al., 1993). Wang et al. (2001) determined the kinetics, fidelity, and stoichiometry of coupling between LCCs and ryanodine receptors. They showed that the local calcium signal produced by a single opening of an LCC, named a 'calcium sparklet,' can trigger about 4 to 6 ryanodine receptors to generate a calcium spark. The coupling between LCCs and ryanodine receptors is stochastic, as judged by the exponential distribution of the coupling latency. The fraction of sparklets that successfully triggers a spark is less than unity and declines in a use-dependent manner. </p><p>Ducreux et al. (2004) found that activation of RYR1 caused release of interleukin-6 (IL6; 147620) from cultured human myotubes. Maximal release was obtained 4 to 6 hours later, suggesting that IL6 was newly transcribed and synthesized. </p><p>Epigenetic regulation of gene expression is a source of genetic variation, which can mimic recessive mutations by creating transcriptional haploinsufficiency. Germline epimutations and genomic imprinting are typical examples. Genomic imprinting can be tissue-specific, with biallelic expression in some tissues and monoallelic expression in others or with polymorphic expression in the general population. During the RYR1 mutation analysis of a cohort of patients with recessive core myopathies, Zhou et al. (2006) discovered that 6 (55%) of 11 patients had monoallelic RYR1 transcription in skeletal muscle, despite being heterozygous at the genomic level. In families for which parental DNA was available, segregation studies showed that the nonexpressed allele was maternally inherited. Transcription analysis in patients' fibroblasts and lymphoblastoid cell lines indicated biallelic expression, which suggested tissue-specific silencing. Transcription analysis of normal human fetal tissues showed that RYR1 is monoallelically expressed in skeletal and smooth muscle, brain, and eye in 10% of cases. In contrast, 25 normal adult human skeletal muscle samples displayed only biallelic expression. Finally, the administration of the DNA methyltransferase inhibitor 5-aza-deoxycytidine to cultured patient skeletal muscle myoblasts reactivated the transcription of the silenced allele, which suggested hypermethylation as a mechanism for RYR1 silencing. The data indicated that RYR1 undergoes polymorphic, tissue-specific, and developmentally regulated allele silencing and that this unveils recessive mutations in patients with core myopathies. The data also suggested that imprinting is a likely mechanism for this phenomenon and that similar mechanisms could play a role in human phenotypic heterogeneity. Klein et al. (2012) found that some of the patients reported by Zhou et al. (2006) with apparent mutations expressed monoallelically in the skeletal muscle were found to have another stop RYR1 mutation, resulting in nonsense-mediated mRNA decay and lack of expression. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Phillips et al. (1996) reported that the RYR1 gene contains 106 exons, of which 2 are alternatively spliced. The length of the gene was estimated to be approximately 160 kb. The numbering of the nucleotides comprising the RYR1 cDNA and the numbering of amino acids encoded by them were corrected to account for earlier errors and omissions. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
Tung et al. (2010) showed the 2.5-angstrom resolution crystal structure of a region spanning 3 domains of RyR1, encompassing amino acid residues 1-559. The domains interact with each other through a predominantly hydrophilic interface. Docking in RyR1 electron microscopy maps unambiguously places the domains in the cytoplasmic portion of the channel, forming a 240-kD cytoplasmic vestibule around the 4-fold symmetry axis. Tung et al. (2010) pinpointed the exact locations of more than 50 disease-associated mutations in full-length RyR1 and RyR2 (180902). The mutations can be classified into 3 groups: those that destabilize the interfaces between the 3 amino-terminal domains, disturb the folding of individual domains, or affect 1 of the 6 interfaces with other parts of the receptor. Tung et al. (2010) proposed a model whereby the opening of RyR coincides with allosterically couples motions within the N-terminal domains. This process can be affected by mutations that target various interfaces within and across subunits. Tung et al. (2010) suggested that the crystal structure provides a framework to understand the many disease-associated mutations in RyRs that have been studied using functional methods, and would be useful for developing new strategies to modulate RyR function in disease states. </p><p>Using electron cryomicroscopy, Efremov et al. (2015) determined the architecture of rabbit Ryr1 at a resolution of 6.1 angstroms and showed that the cytoplasmic moiety of Ryr1 contains 2 large alpha-solenoid domains and several smaller domains, with folds suggestive of participation in protein-protein interactions. The transmembrane domain represents a chimera of voltage-gated sodium and pH-activated ion channels. Efremov et al. (2015) identified the calcium-binding EF-hand domain and showed that it functions as a conformational switch allosterically gating the channel. </p><p>Zalk et al. (2015) reported the closed-state structure of the 2.3-megadalton complex of rabbit Ryr1, solved by single-particle electron cryomicroscopy at an overall resolution of 4.8 angstroms. They fitted a polyalanine-level model to all 3,757 ordered residues in each protomer, defining the transmembrane pore in great detail and placing all cytosolic domains as tertiary folds. The cytosolic assembly is built on an extended alpha-solenoid scaffold connecting key regulatory domains to the pore. The Ryr1 pore architecture places it in the 6-transmembrane ion channel superfamily. A unique domain inserted between the second and third transmembrane helices interacts intimately with paired EF hands originating from the alpha-solenoid scaffold, suggesting a mechanism for channel gating by calcium. </p><p>Yan et al. (2015) reported the structure of rabbit Ryr1 in complex with its modulator FKBP12 (186945) at an overall resolution of 3.8 angstroms, determined by single-particle electron cryomicroscopy. Three domains, named central, handle, and helical domains, display the armadillo repeat fold. These domains, together with the amino-terminal domain, constitute a network of superhelical scaffold for binding and propagation of conformational changes. The channel domain exhibits the voltage-gated ion channel superfamily fold with distinct features. A negative charge-enriched hairpin loop connecting S5 and the pore helix is positioned above the entrance to the selectivity-filter vestibule. The 4 elongated S6 segments form a right-handed helical bundle that closes the pore at the cytoplasmic border of the membrane. Allosteric regulation of the pore by the cytoplasmic domains is mediated through extensive interactions between the central domains and the channel domain. Yan et al. (2015) concluded that these structural features explain high ion conductance by ryanodine receptors and the long-range allosteric regulation of channel activities. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By in situ hybridization, MacLennan et al. (1989) localized the RYR1 gene to chromosome 19cen-q13.2. By fluorescence in situ hybridization, Trask et al. (1993) assigned the RYR1 gene to 19q13.1. MacKenzie et al. (1990) mapped the RYR1 gene to 19q13.1, distal to GPI (172400) and MAG (159460). </p><p>Using somatic cell hybrids, Harbitz et al. (1990) regionalized the porcine Ryr1 gene (termed CRC by them) to chromosome 6p11-q21. The authors noted homology of synteny with the genes on human chromosome 19. </p><p>Cavanna et al. (1990) demonstrated that the Ryr gene in the mouse maps to chromosome 7. By in situ hybridization, Mattei et al. (1994) mapped the mouse Ryr1 gene to 7A2-7A3. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Robinson et al. (2006) provided a detailed review of mutations in the RYR1 gene. </p><p><strong><em>Susceptibility to Malignant Hyperthermia</em></strong></p><p>
|
|
In several porcine breeds that exhibited inheritance of malignant hyperthermia (145600), Otsu et al. (1991) and Fujii et al. (1991) identified a mutation in the Ryr1 gene (R615C). In 1 of 35 Canadian families with malignant hyperthermia, Gillard et al. (1991) identified the same mutation, which is R614C (180901.0001) in humans. </p><p>In patients with malignant hyperthermia, Manning et al. (1998) identified 4 adjacent mutations in the RYR1 gene: R2163C (180901.0010), R2163H (180901.0011), V2168M (180901.0013), and T2206M (180901.0014). </p><p>Brandt et al. (1999) stated that 21 RYR1 mutations had been identified in families with malignant hyperthermia, 4 of which were also associated with central core myopathy. By screening for these 21 mutations in 105 MH families, including 10 families with central core disease (CCD) (CMYO1A; 117000), phenotyped by the IVCT according to the European protocol, the authors determined the approximate mutation frequencies, with R614C (9%; 180901.0001) and G2434R (7%; 180901.0007) being the most common mutations. Brandt et al. (1999) also detected 2 novel mutations, each in a single pedigree. In the 109 individuals of the 25 families with RYR1 mutations, cosegregation between genetic result and IVCT was almost perfect. Only 3 genotypes were discordant with the IVCT phenotypes, suggesting a true sensitivity of 98.5% and a specificity of minimally 81.8% for this test. Screening of the transmembrane region of RYR1 did not yield a new mutation, confirming the cytosolic portion of the protein to be of main functional importance for pathogenesis. </p><p>Sambuughin et al. (2001) reported that malignant hyperthermia susceptibility (MHS) had been found to be associated with 30 different mutations in the RYR1 gene, all of which represent single-nucleotide changes. </p><p>Monnier et al. (2005) reported the results of correlation studies performed with molecular, pharmacologic, histologic, and functional data obtained from 176 families, 129 referred to as 'confirmed' and 46 as 'potential' MHS families. Extensive molecular analysis allowed them to identify a variant in 60% of the confirmed MHS families and resulted in the characterization of 11 new variants in the RYR1 gene. Most of the mutations clustered in the MH1 (52%) and MH2 (36%) domains of the RYR1 gene. </p><p>Johnston et al. (2021) reported an adaptation of the American College of Medical Genetics/Association for Molecular Pathology (ACMG/AMP) pathogenicity criteria by a variant curation expert panel for the classification of RYR1 variants in malignant hyperthermia susceptibility. Using the new criteria, 44 RYR1 gene mutations previously determined to be diagnostic by the European Malignant Hyperthermia Group (EMHG) were categorized: 29 were classified as pathogenic, 13 as likely pathogenic, and 2 as variants of unknown significance. Johnston et al. (2021) concluded that use of the new criteria should allow for more consistent classification of RYR1 mutations. </p><p><strong><em>Autosomal Dominant Congenital Myopathy 1A With Susceptibility to Malignant Hyperthermia</em></strong></p><p>
|
|
In affected members of a large multigenerational Canadian family with autosomal dominant congenital myopathy-1A (CMYO1A; 117000) with central core disease on skeletal muscle biopsy (CCD) and susceptibility to malignant hyperthermia originally reported by Shuaib et al. (1987), Zhang et al. (1993) identified a heterozygous missense mutation in the RYR1 gene (R2435H; 180901.0003). </p><p>In 2 Italian brothers (family 4T) with CMYO1A manifest as central core disease (CCD) on skeletal muscle biopsy, Quane et al. (1993) identified a heterozygous missense mutation in the RYR1 gene (I403M; 180901.0005). The clinically unaffected father also carried the mutation; he did not undergo muscle biopsy. In 4 members of another Italian family (2T) with variable expression of CMYO1A and malignant hyperthermia, Quane et al. (1993) identified a heterozygous mutation in the RYR1 gene (R163C; 180901.0004). Of note, Quane et al. (1993) also identified the R163C mutation in a Danish family (D15) in which a mother and her 2 children had MHS without clinical signs of a myopathy and absence of cores on muscle biopsy. These findings demonstrated phenotypic variability, both within families and between families with the same mutation. </p><p>Lynch et al. (1999) studied a large Mexican kindred in which all affected members had a clinically severe and highly penetrant form of CMYO1A. Sequencing of the entire RYR1 cDNA in an affected member identified a single heterozygous mutation in the C-terminal transmembrane/luminal domain of the protein (180901.0012). The introduction of this mutation into a recombinant RyR1 protein expressed in HEK293 cells resulted in loss of channel activation by caffeine and halothane and a significant reduction in ryanodine binding. These and additional findings, which pointed to a high basal activity of the mutant Ca(2+) channel, could explain the muscle weakness and muscle atrophy observed in CCD patients in this family. </p><p>Scacheri et al. (2000) identified a heterozygous mutation in the RYR1 gene (180901.0030) in affected members of a large family with CMYO1A. Skeletal muscle biopsies from 2 affected individuals showed the presence of central cores in over 85% of myofibers and nemaline rods in 5 to 25% of myofibers. Scacheri et al. (2000) suggested that nemaline bodies may be a secondary feature in this disorder. </p><p>In 5 members of a French family with CMYO1A, Monnier et al. (2000) identified a heterozygous missense mutation in the RYR1 gene (Y4796C; 180901.0016). The mutation occurs in the C-terminal channel-forming domain of the RYR1 protein. Expression of the mutant RYR1 cDNA in rabbit HEK293 cells produced channels with increased caffeine sensitivity, cells with increased resting cytoplasmic Ca(2+) levels, and a significantly reduced maximal level of Ca(2+) release, suggesting an increased rate of Ca(2+) leakage in the mutant channel. The authors hypothesized that the resulting chronic elevation in myoplasmic Ca(2+) concentration may be responsible for the severe phenotype in this family. Haplotype analysis indicated that the mutation arose de novo in the proband. </p><p>In affected members of 16 unrelated families with CMYO1A, Monnier et al. (2001) identified 12 different missense mutations in the C-terminal domain of RYR1 (see, e.g., I4898T, 180901.0012; V2168M, 180901.0013; a 9-bp del, 180901.0018; R4861H, 180901.0019; and R4893W, 180901.0044). Since the muscle symptoms in the families suggested a defect in Ca(2+) homeostasis, the authors sequenced exons in the C-terminal channel-forming domain of RYR1, which is involved in Ca(2+) movement. V2168M occurred in exon 39, but all of the other mutations occurred in exons 91 through 102. Four de novo mutations were found, indicating that de novo mutations in RYR1 are not rare and may confound genetic studies of families that present with congenital myopathies. Functional studies of the mutations were not performed. Molecular modeling based on a 4-transmembrane domain model suggested that the mutations concentrated mostly in the myoplasmic and luminal loops linking, respectively, transmembrane domains T1 and T2 or T3 and T4 of RYR1 and may therefore affect the excitation-contraction process in skeletal muscle. The patients were ascertained from a cohort of 34 families with congenital myopathy associated with central cores on muscle biopsy who underwent genetic analysis; RYR1 mutations were found in 47% of families. </p><p>Tilgen et al. (2001) screened the C-terminal domain of the RYR1 gene for mutations in 50 European patients diagnosed clinically and/or histologically as having congenital myopathy with central cores on biopsy (central core disease, CCD). Four novel missense mutations (see, e.g., 180901.0012 and 180901.0019) were identified in 13 of 25 index patients. The mutations clustered in exons 101 and 102 and replaced conserved amino acids. Lymphoblasts derived from patients carrying these C-terminal RYR1 mutations exhibited a release of calcium from intracellular stores in the absence of any pharmacologic activators of RYR; significantly smaller thapsigargin-sensitive intracellular calcium stores, compared to lymphoblasts from control individuals; and a normal sensitivity of the calcium release to the RYR inhibitor dantrolene. The authors suggested that the C-terminal domain of RYR1 may be a hotspot for mutations leading to the CCD phenotype. </p><p>Zorzato et al. (2003) identified a patient with severe CCD and her mother with mild CCD who were both heterozygous for a deletion (amino acids 4863-4869; 180901.0024) in the pore-forming region of the sarcoplasmic reticulum calcium release channel. The deleted amino acids form part of the luminal loop connecting membrane-spanning segments M8 and M10 and are conserved in all known vertebrate RYR1 isoforms. Lymphoblastoid cells carrying the RYR1 deletion exhibited an 'unprompted' calcium release from intracellular stores, resulting in significantly smaller thapsigargin-sensitive intracellular Ca(2+) stores compared with lymphoblastoid cells from controls. Blocking the RYR1 with dantrolene restored the intracellular calcium stores to levels similar to those found in controls. Single-channel and [3H]ryanodine-binding measurements in HEK293 cells heterologously expressing mutant channels revealed a reduced ion conductance and loss of ryanodine binding and regulation by Ca(2+). </p><p>In 11 patients from 4 unrelated families with CMYO1A, Quinlivan et al. (2003) identified heterozygous mutations in the RYR1 gene (see, e.g., R4861H, 180901.0019; R4893W, 180901.0044; and Y4864C, 180901.0045). All mutations occurred in region 3 of the RYR1 gene. The mutation was inherited in an autosomal dominant pattern in 3 families (families A, B, and C), whereas the mutation occurred de novo in the proband from family D. </p><p>In 4 unrelated Japanese patients with CMYO1A and a pathologic diagnosis of congenital neuromuscular disease with uniform type 1 fiber (CNMDU1), Sato et al. (2008) identified heterozygous mutations in the RYR1 gene (see, e.g., 180901.0019; 180901.0033-180901.0034). The father of 1 patient had the same mutation as his son (180901.0033) and was diagnosed with CCD (Wu et al., 2006; Tojo et al., 2000), indicating that RYR1 mutations can cause variable findings on skeletal muscle biopsy. </p><p><strong><em>Autosomal Recessive Congenital Myopathy 1B</em></strong></p><p>
|
|
In affected members of a consanguineous Algerian family with autosomal recessive congenital myopathy-1B (CMYO1B; 255320) characterized by the presence of multiple, short-length core lesions (minicores) on skeletal muscle biopsy, Ferreiro et al. (2002) identified a homozygous missense mutation in the RYR1 gene (P3527S; 180901.0021). Three children in the family presented in infancy with moderate weakness predominant in axial muscles, pelvic girdle, and hands, joint hyperlaxity, and multiple minicores on skeletal muscle biopsy. New muscle biopsies from the 3 patients in adulthood demonstrated central core disease with rods; no cores were found in the healthy parents. </p><p>In a 19-year-old girl, born of consanguineous parents (family 1), with CMYO1B, Jungbluth et al. (2002) identified a homozygous missense mutation in the RYR1 gene (V4849I; 180901.0022). In a 9-year-old girl, born of consanguineous parents, with autosomal recessive CMYO1B and central core disease on muscle biopsy, Kossugue et al. (2007) identified a homozygous V4849I substitution in the RYR1 gene. </p><p>Monnier et al. (2003) and Jungbluth et al. (2005) identified biallelic mutations in the RYR1 gene (see, e.g., 180901.0025-180901.0029) in patients with CMYO1B manifest as minicore myopathy with external ophthalmoplegia. </p><p>Monnier et al. (2008) reported a 9-year-old Dutch boy with a severe autosomal recessive myopathy with ptosis and facial diplegia associated with compound heterozygous mutations in the RYR1 gene: V4849I and a 4-bp insertion (180901.0032). Monnier et al. (2008) postulated that since the patient had a hypomorphic frameshift RYR1 allele, the resultant phenotype was more severe compared to those patients with homozygous V4849I mutations. </p><p>In 17 patients, all from unrelated nonconsanguineous families, with CMYO1B and a clinicopathologic diagnosis of centronuclear myopathy (CNM), Wilmshurst et al. (2010) identified mutations in the RYR1 gene (see, e.g., 180901.0035-180901.0037). Compound heterozygosity for a nonsense and missense mutation was found in all except 3 patients, in whom a second pathogenic allele could not be found. The phenotype was characterized by onset at birth, neonatal hypotonia and weakness, delayed motor development, external ophthalmoplegia, and bulbar involvement. In addition to central nuclei, prominent histopathologic findings included multiple internalized nuclei, type 1 fiber predominance and hypotrophy, relative type 2 hypertrophy, and oxidative abnormalities in electron microscopic analysis, although frank cores were not typically seen. Twelve of the patients were from South Africa, and haplotype analysis suggested founder effects for some of the mutant alleles. The 17 patients were ascertained from a larger group of 24 patients with a diagnosis of CNM, indicating that RYR1 mutations can account for this subtype of myopathy. Wilmshurst et al. (2010) postulated that disorder resulted from disturbed assembly and/or malfunction of the excitation-contraction machinery. </p><p>In 3 (8.3%) of 36 families with CMYO1B manifest as fetal akinesia deformation/lethal pterygium syndrome, McKie et al. (2014) identified 3 different homozygous nonsense or intragenic deletion mutations in the RYR1 gene (180901.0039-180901.0041). McKie et al. (2014) suggested that RYR1 mutation analysis should be performed in cases with severe early lethal fetal akinesia even in the absence of specific histopathologic indicators of RYR1-related disease. </p><p><strong><em>King-Denborough Syndrome</em></strong></p><p>
|
|
In a patient with King-Denborough syndrome (KDS; 619542), D'Arcy et al. (2008) identified a heterozygous mutation in the RYR1 gene (180902.0038). </p><p>By direct RYR1 sequencing, Dowling et al. (2011) identified heterozygous missense mutations in 4 patients with KDS, a 6-year-old boy (T2203M; 180901.0014) and 3 members of 1 family (R2452W; 180901.0042). In a patient with severe kyphoscoliosis, moderate proximal weakness, and distal joint laxity, Dowling et al. (2011) identified heterozygosity for an S2776F mutation in the RYR1 gene; however, her father, who also had the mutation, was asymptomatic. Dowling et al. (2011) concluded that the S2776F mutation was probably pathogenic but not sufficient to cause the patient's phenotype. </p><p>In a 2-year-old boy with KDS, Joseph et al. (2017) identified a heterozygous missense mutation in the RYR1 gene (R2508C; 180901.0043). Functional studies were not performed. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Manning et al. (1998) tabulated the 17 mutations that had been identified in the RYR1 gene in families with MHS and CCD. They estimated that the 4 novel mutations they found accounted for approximately 11% of MH cases. The 13 that had been identified before their study were located in 2 regions, the N-terminal and central regions. Their study and that of others indicated that the gene segment 6400-6700 is a mutation hotspot. Two different amino acid substitutions had been identified in each of 3 codons: 614, 2163, and 2458. Correlation analysis of IVCT data available for pedigrees bearing these 17 RYR1 mutations showed an exceptionally good correlation between caffeine threshold and tension values, whereas no correlation was observed between halothane threshold and tension values. The findings indicated that assessment of recombinant individuals on the basis of caffeine response is justified, whereas assessment on the basis of halothane response may be problematic, and suggested a link between the caffeine threshold and tension values and the MH/CCD phenotype. </p><p>McCarthy et al. (2000) noted that the majority of RYR1 mutations appeared to be clustered in the N-terminal amino acid residues 35-614 (referred to as the MH/CCD region-1) and the centrally located residues 2163-2458 (MH/CCD region-2). The only mutation identified outside of these regions was a single mutation associated with a severe form of CCD in the highly conserved C terminus of the gene, I4898T (180901.0012). All of the RYR1 mutations result in amino acid substitutions in the myoplasmic portion of the protein, with the exception of the mutation in the C terminus, which resides in the luminal/transmembrane region. The likely deciding factors in determining whether a particular RYR1 mutation results in MHS alone or MHS and CCD are sensitivity of the RYR1 mutant proteins to agonists; the level of abnormal channel-gating caused by the mutation; the consequential decrease in the size of the releasable calcium store and increase in resting concentration of calcium; and the level of compensation achieved by the muscle with respect to maintaining calcium homeostasis. </p><p>Robinson et al. (2002) stated that 15 RYR1 N-terminal mutations are considered causative of MHS, and that 5 of these are also associated with CCD. In an extensive U.K. population survey, they detected 8 of these 15 mutations in 85 of 297 (29%) unrelated MH susceptibility cases, with G2434R (180901.0007) detected in 53 cases (18%). R163C (180901.0004), R2163H (180901.0011), and R2435H (180901.0003), RYR1 mutations associated with both CCD and MH, had more severe caffeine and halothane response phenotypes than those associated with MH alone. Mutations near the N terminus (R163C; G341R, 180901.0006) had a relatively greater effect on response to caffeine than halothane, with a significantly increased caffeine:halothane tension ratio compared to G2434R of the central domain. All phenotypes were more severe in males than females, and were also affected by muscle specimen size and viability. Discordance between RYR1 genotype and IVCT phenotype was observed in 7 families (9 individuals), with 5 false-positives and 4 false-negatives. The clinical and genetic data in this study demonstrated that RYR1 mutations involved in CCD are those associated with 1 end of the spectrum of MH IVCT phenotypes. </p><p>Ducreux et al. (2004) found that cultured human myotubes with the I4898T mutation in the RYR1 gene (180901.0012), which is in the C-terminal hydrophobic membrane-spanning region of the protein and causes CCD, had a 4-fold increase in background levels of IL6 in the absence of RYR1 activation compared to controls; cells with the V2168M (180901.0013) mutation, which causes MHS, had background IL6 levels similar to control cells. In addition, cells with the CCD mutation had significantly less agonist-induced calcium release from intracellular stores compared to control cells or MHS cells. The findings indicated that mutations in the C-terminal domain reduce the amount of calcium released via the RYR1 channel, resulting in altered excitation-contraction coupling. Release of IL6, an inflammatory and pyrogenic cytokine, may affect signaling pathways responsible for muscle fiber abnormalities in CCD. </p><p>Lyfenko et al. (2004) reviewed the dynamic alterations in myoplasmic calcium metabolism in disorders caused by mutation in the RYR1 gene, and discussed molecular mechanisms by which these genetic defects lead to distinct clinical and histopathologic manifestations. Benkusky et al. (2004) reviewed RYR1 and RYR2 mutations and their role in muscle and heart disease, respectively. </p><p>Klein et al. (2012) noted that dominant mutations involved in congenital myopathy-1A (CMYO1A; 117000) are mostly confined to the C-terminal region of the gene, particularly region 3, whereas mutations involved in MHS are mostly detected in regions 1 and 2 within the N terminal. Most dominant mutations are missense. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>McCarthy et al. (2000) pointed out that the RYR1 G341R mutation (180901.0006) is present in about 6% of Irish/English/French families, but is rare in northern Europe. The R614C mutation (180901.0001) is more common in German families (9%), while the V2168M (180901.0013) mutation is common in Swiss families but relatively rare otherwise. </p><p>Monnier et al. (2005) found that the RYR1 R614C mutation is the most prevalent mutation in French families with MHS, whereas it is poorly represented in affected families from the U.K. In contrast, the G2434R (180901.0007) and V2168M (180901.0013) mutations, which are the most prevalent in MHS families from the U.K. (Robinson et al., 2002) and Switzerland (Girard et al., 2001), respectively, are present at a much lower level in affected French families. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In several porcine breeds exhibiting inheritance of malignant hyperthermia, Otsu et al. (1991) and Fujii et al. (1991) identified a 1843C-T transition in the RYR1 gene, resulting in an arg615-to-cys (R615C) substitution. The same mutation was found in 5 major breeds (see Harbitz et al. (1992) for a sixth) of lean, heavily muscled swine, and haplotyping suggested that the mutation in all had a common origin, demonstrating a founder effect in these animals. Fujii et al. (1991) suggested that the mutation had been selected for by breeders because it was associated with lean and heavy muscles. The porcine R615C mutation corresponds to the R614C mutation identified in humans with malignant hyperthermia (180901.0001). </p><p>Takeshima et al. (1994) developed mice with a targeted mutation in the Ryr1 gene. Homozygous mice died perinatally with gross abnormalities of skeletal muscle. The contractile response to electrical stimulation under physiologic conditions was totally abolished in mutant embryonic muscle. However, ryanodine receptors other than Ryr1 seemed to exist, because a response to caffeine was retained. Takeshima et al. (1994) concluded that RYR1 is essential for both muscular maturation and excitation-contraction coupling and that RYR1 function during excitation-contraction coupling cannot be substituted by other receptor subtypes. </p><p>Takeshima et al. (1995) demonstrated that the residual caffeine-activated calcium release in Ryr1 null mice is likely mediated by Ryr3 (180903). </p><p>Barone et al. (1998) generated double mutant mice carrying a targeted disruption of both the Ryr1 and the Ryr3 (180903) genes. Skeletal muscles from mice homozygous for both mutations did not contract in response to caffeine or ryanodine. In addition, these muscles showed very low tension when directly activated with micromolar ionized calcium after membrane permeabilization, indicating either poor development or degeneration of the myofibrils. This was confirmed by biochemical analysis of contractile proteins. Electron microscopy confirmed small size of myofibrils and showed complete absence of ryanodine receptors in the junctional sarcoplasmic reticulum. </p><p>Chelu et al. (2006) found that mice with a homozygous for the Y522S (180901.0031) mutation in the Ryr1 gene exhibited skeletal defects and died during embryonic development or soon after birth. Heterozygous mice, corresponding to the human occurrence of this mutation, were susceptible to malignant hyperthermia and showed whole body contractions and elevated core temperatures in response to isoflurane exposure or heat stress. Skeletal muscles from heterozygous mice exhibit increased susceptibility to caffeine- and heat-induced contractures in vitro. In addition, the heterozygous expression of the mutation resulted in enhanced RyR1 sensitivity to activation by temperature, caffeine, and voltage but not uncompensated sarcoplasmic reticulum calcium leak or store depletion. </p><p>Durham et al. (2008) found that skeletal muscle from heterozygous Y522S-mutant mice displayed increased basal oxidative stress with increased levels of reactive oxygen and nitrogen species compared to wildtype mice. Further studies suggested that the reactive species resulted from increased calcium release from the leaky mutant RyR1 channel in resting muscles. Increased calcium combined with increased reactive nitrogen species produced S-nitrosylation of the mutant leaky channel that further enhanced channel activity at increased temperatures. Durham et al. (2008) postulated a destructive feed-forward cycle of increased calcium release, increased temperature-sensitivity of the mutant channel, and increased muscle contraction with elevated temperature and heat stress. Over time, this cycle induced a myopathy characterized by damaged mitochondria and decreased force generation. </p><p>Bellinger et al. (2009) found that the Ryr1 channel in skeletal muscle from the mdx mouse, a model of Duchenne muscular dystrophy (DMD; 310200) with disruption of the dystrophin gene (DMD; 300377), showed increased inducible nitric oxide (NOS2A; 163730)-mediated S-nitrosylation of cysteine residues, which depleted the channel complex of calstabin-1 (FKBP12; 186945). This resulted in leaky channels with increased calcium flux. These changes were age-dependent and coincided with dystrophic changes in muscle. Prevention of calstabin-1 depletion from Ryr1 with S107, a compound that binds the Ryr1 channel and enhances binding affinity, inhibited sarcoplasmic reticulum calcium leak, reduced biochemical and histologic evidence of muscle damage, improved muscle function, and increased exercise performance in mdx mice. Bellinger et al. (2009) proposed that the increased calcium flux via a defective Ryr1 channel contributes to muscle weakness and degeneration in DMD by increasing calcium-activated proteases. </p><p>To understand the skeletal muscle pathology in patients with an RYR1 mutation that results in decreased RYR1 protein content (e.g., Q1979X), Elbaz et al. (2019) generated a mouse model with a heterozygous mutation in exon 36 (Gln1970fsTer16) of the Ryr1 gene. Mice heterozygous for the mutation had lower running distance before and after exercise training, and lower median cruise speed, compared to wildtype littermates. Ryr1 protein content was lower in mutant mice compared to wildtype in the extensor digitorum longus (EDL) (37.6% of wildtype) and soleus muscles (58.7% of wildtype), and gene transcript levels were 50% of wildtype levels. Electron microscopy studies in EDL muscles from mutant mice showed an uneven distribution and abnormal morphology of calcium release units (CRUs), including an increase of CRUs with only 2 elements, suggesting a reduction in the number of calcium release sites. Functional studies showed that muscle strength and depolarization-induced calcium transients were reduced in mutant mice, at 20% and 15% of wildtype, respectively. Because the level of Ryr1 protein content was quantitatively more abnormal than strength and peak calcium transient deficiencies in the mutant mice, Elbaz et al. (2019) suggested that there may be an adaptation to chronic Ryr1 protein deficiency. </p><p>Elbaz et al. (2019) generated a mouse model with compound heterozygous mutations in RYR1, Q1970fsX16 in exon 36 and A4329D in exon 91, which are isogenic to the RYR1 mutations identified in a severely affected child with autosomal recessive multiminicore disease (see 255320). Both Ryr1 protein and transcript levels were reduced in muscle from the mutant mice, and Hdac4 protein (605314) was found to be upregulated. Compared to their wildtype littermates, mutant mice had lower body weight at age 18 weeks, and lower spontaneous running distance and cruising speed at age 3 months. Histologic examination of mutant muscles showed regions of severe myofibrillar disorganization as well as reduced numbers of calcium release units (CRUs) and mitochondria. Functional testing showed that the mutant muscles developed less isometric force and had smaller evoked calcium transients. Elbaz et al. (2019) concluded that the mutant mice recapitulated the clinical features seen in patients with multiminicore disease and provided insight into the pathologic mechanism of the disease. </p><p>Brennan et al. (2019) generated a compound heterozygous mouse model of RYR1-related myopathy (RYR1-RM) in which one allele of Ryr1 had a thr4709-to-met (T4709M) mutation, equivalent to human T4706M, and the other allele had a 16-bp frameshift deletion in exon 96. Mutant mice were born at the expected mendelian frequency, although a small number died during the first 3 days of life. Mutant mice that survived beyond 3 days exhibited reduced body weight due to a substantial reduction of the myofiber compartment. The disease progressed rapidly, with most mice dying before 57 days of age due to respiratory failure caused by spine changes and muscle weakness. Mutant mice exhibited reduced muscle force generation, and mutant muscles had decreased myofiber size but preserved muscle structure. Levels of Ryr1 and Dhpr (QDPR; 612676) proteins were reduced in mutant muscles, and combined with reduced muscle force generation, this reduction led to aberrant intracellular calcium dynamics in mutant mice. Knockin mice homozygous for the T4709M mutation displayed a potentially lethal hyperthermic response during isoflurane exposure, recapitulating the enhanced sensitivity to volatile anesthetics seen in RYR1-RM patients with malignant hyperthermia. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>45 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, ARG614CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192172,
|
|
|
|
|
|
gnomAD: rs118192172,
|
|
|
|
|
|
ClinVar: RCV000013830, RCV000119586, RCV000538121, RCV000608635, RCV000624176, RCV001787388, RCV001787389, RCV001787390, RCV001787391, RCV001787392, RCV001787393, RCV001787394, RCV002496349
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 members of 1 of 35 Canadian families with malignant hyperthermia (MHS1; 145600), Gillard et al. (1991) identified a heterozygous c.1840C-T transition in the RYR1 gene, resulting in an arg614-to-cys (R614C) substitution, which is comparable to the R615C mutation found in pigs with malignant hyperthermia (see ANIMAL MODEL). Of the mutation carriers, the proband experienced an episode of malignant hyperthermia during surgery, and the other 2 (her mother and sister) had positive muscle biopsy contracture tests. The proband's father and brother, who did not carry the mutation, had negative contracture tests. </p><p>Hall-Curran et al. (1993) did not identify the R614C mutation in in 100 British families with malignant hyperthermia, suggesting that the prevalence of this mutation is less than 3% in the U.K. population. The authors concluded that presymptomatic testing for R614C, as suggested by Otsu et al. (1992), would have no practicality in the British population. </p><p>In a German family with MHS, Deufel et al. (1995) identified the R614C mutation in homozygosity or heterozygosity in affected individuals. In vitro contracture test (IVCT) phenotypes were similar between heterozygotes and 1 homozygous individual (408). The mutation was present on 2 different haplotypes in the family. In addition, 3 individuals with MHS in a different branch of the family did not carry the R614C mutation; IVCT results for these affected individuals did not differ from those carrying the R614C mutation. The authors suggested that the results may challenge the causative role of the mutation and possibly the role of the RYR1 gene itself in human malignant hyperthermia susceptibility, at least in some cases. </p><p>Fagerlund et al. (1994, 1995) found the R614C mutation in 3 of 41 Swedish families with MHS, but in none of 48 Danish families. </p><p>Fagerlund et al. (1997) reported 2 families in which there was recombination between MH susceptibility and the R614C mutation, in 1 and 3 individuals, respectively. They suggested that these findings make it necessary to reconsider the specificity of the in vitro contracture test (IVCT) and/or the role of R614C as a cause of MH susceptibility in some families exhibiting this mutation. </p><p><strong><em>Variant Function</em></strong></p><p>
|
|
Otsu et al. (1994) designed experiments to demonstrate physiologically that the R614C mutation alters ryanodine receptor function. They estimated cytoplasmic calcium ion responses to halothane and caffeine in myoblastic cells expressing the normal or mutant ryanodine receptor by transfecting the corresponding cDNAs. Exposure to clinical doses of halothane resulted in a rapid increase in calcium ion in cells expressing the mutant receptor, whereas no calcium changes were observed in cells expressing the wildtype receptor. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, GLY248ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1801086,
|
|
|
|
|
|
gnomAD: rs1801086,
|
|
|
|
|
|
ClinVar: RCV000013831, RCV000119713, RCV001851834, RCV004017237
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs (TJ and SJ, family 39) with malignant hyperthermia (MHS1; 145600), Gillard et al. (1992) identified a heterozygous G-to-A transition in the RYR1 gene that resulted in a gly248-to-arg (G248R) substitution. The mutation was identified by PCR amplification followed by direct sequencing. The proband, TJ, experienced an episode of malignant hyperthermia while undergoing tonsillectomy, and also had muscle cramps. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT, WITH SUSCEPTIBILITY TO MALIGNANT HYPERTHERMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, ARG2435HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933396,
|
|
|
|
|
|
|
|
ClinVar: RCV000013832, RCV000119699, RCV000707405, RCV001787395, RCV001787396, RCV001787397, RCV001787398, RCV001787399, RCV001787400, RCV001787401, RCV002281705, RCV004017238
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a large Canadian family with congenital myopathy-1A (CMYO1A; 117000) manifest as central core disease on skeletal muscle biopsy, Zhang et al. (1993) identified a heterozygous c.7301G-A transition in the RYR1 gene, resulting in an arg2434-to-his (ARG2434HIS) substitution. This appeared to be a 'private' mutation since it was restricted to this single large family among more than 100 Canadian CCD and MHS families tested. Some members of the family had previously been reported by Shuaib et al. (1987) as having mild myopathy, central cores on muscle biopsy, and susceptibility to malignant hyperthermia. </p><p>Richter et al. (1997) referred to this mutation as arg2435-to- his (R2435H), according to the revised numbering of amino acids based on the corrected sequence data of Phillips et al. (1996). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT, WITH SUSCEPTIBILITY TO MALIGNANT HYPERTHERMIA, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, ARG163CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192161,
|
|
|
|
|
|
|
|
ClinVar: RCV000013833, RCV000013834, RCV000119625, RCV000806352, RCV001787402, RCV001787706, RCV001787707, RCV001787708, RCV001787709, RCV001787710, RCV001787711, RCV004017239
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 2 unrelated families (2T and D15) with susceptibility to malignant hyperthermia (MHS1; 145600), Quane et al. (1993) identified heterozygosity for a c.487C-T transition in the RYR1 gene that resulted in an arg163-to-cys (R163C) substitution. In family 2T, some persons also had manifestations of a congenital myopathy (CMYO1A; 117000) with central cores on skeletal muscle biopsy. </p><p>O'Brien et al. (1995) reported a family in which 2 members diagnosed with MHS by means of the in vitro contracture test were found to be heterozygous for the R163C mutation, but 2 other members diagnosed with MHS on the same basis did not have the mutation. Reference was made to other families in which the major phenotype did not cosegregate with the arg614-to-cys (R614C; 180901.0001) or the gly341-to-arg (G341R; 180901.0006) mutations. </p><p>Fagerlund et al. (1994, 1995) found the heterozygous R163C mutation in 1 of 48 Danish families with MHS, but in none of 41 Swedish families. </p><p>Tobin et al. (2001) identified a heterozygous R163C mutation in a 12-year-old boy with MHS. The patient's father also carried the mutation. The boy experienced an episode of MH during surgery for reduction of a humerus fracture, from which he recovered; he died 8 months later after participation in a football game when the ambient temperature was approximately 80 degrees F, with apparent heat stroke (rectal temperature greater than 108 degrees F). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, ILE403MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192116,
|
|
|
|
|
|
gnomAD: rs118192116,
|
|
|
|
|
|
ClinVar: RCV000013835, RCV000119453, RCV001787712, RCV001787713, RCV001787714, RCV001787715, RCV001787716, RCV001787717, RCV001787718, RCV003231102, RCV003591629, RCV004782014
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 affected brothers from an Italian family (4T) with congenital myopathy-1A (CMYO1A; 117000) and central cores on skeletal muscle biopsy, Quane et al. (1993) demonstrated heterozygosity for a c.1209C-G transversion in the RYR1 gene that resulted in an ile403-to-met substitution (I403M). The sibs inherited the mutation from their clinically normal father, who was not available for biopsy. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, GLY341ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918592,
|
|
|
|
|
|
|
|
ClinVar: RCV000013836, RCV000119406, RCV000655541
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected individuals from 3 unrelated families with malignant hyperthermia susceptibility (MHS1; 145600), Quane et al. (1994) identified a heterozygous c.1021G-A transition in the RYR1 gene, resulting in a gly341-to-arg (G341R) substitution. The authors suggested that the G341R mutation may be responsible for approximately 10% of all MHS cases in Caucasians. However, Fagerlund et al. (1996) discovered this mutation in only 1 of 89 Swedish and Danish families with MHS. </p><p>Alestrom et al. (1995) used the amplification-created restriction sites (ACRS) technique to detect the G341R mutation. The method discriminated quickly and efficiently between homozygotes with the mutation, heterozygotes, and homozygotes without the mutation. </p><p>Adeokun et al. (1997) reported a large family in which the G341R mutation did not show complete cosegregation with MHS: it occurred in only 7 of 12 individuals in the kinship demonstrated to be MH sensitive by in vitro contracture tests (IVCTs), and susceptibility was inherited from parents who were homozygous wildtype c.1021G, as well as from parents who were heterozygotes. </p><p>Monsieurs et al. (1998) found that 9 of 13 carriers of the G341R mutation in 2 families had elevated serum creatine kinase levels (up to 6 times the upper limit of normal). All had normal neurologic exams and muscle histology. The third family did not show increased creatine kinase levels. The authors suggested that the G341R mutation may be a cause of chronic elevation of serum creatine kinase in asymptomatic individuals. </p><p>Whereas the G341R mutation is a frequent cause of malignant hyperthermia in European populations, Stewart et al. (1998) did not find the mutation in 114 North American individuals screened because of a family history or personal history of malignant hyperthermia. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, GLY2434ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918593,
|
|
|
|
|
|
gnomAD: rs121918593,
|
|
|
|
|
|
ClinVar: RCV000013837, RCV000119698, RCV000551243, RCV000612258, RCV001787719, RCV001787720, RCV001787721, RCV001787722, RCV001787723, RCV001787724, RCV001787725, RCV002288488, RCV002513026, RCV005025050
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected individuals from 4 of 104 unrelated families with malignant hyperthermia susceptibility (MHS1; 145600), Keating et al. (1994) identified a heterozygous gly2433-to-arg (GLY2433ARG) change in the RYR1 gene resulting from a c.7297G-A transition. The authors noted that this mutation is adjacent to the R2434H mutation (180901.0003), which may indicate a second cluster in the RYR1 gene where MHS and/or central core disease (CMYO1A; 117000) mutations occur. </p><p>In the numbering system of amino acids provided by the corrected sequence data for human RYR1 according to Phillips et al. (1996), this mutation was referred to as G2434R by Richter et al. (1997). Functional studies showed that the G2434R mutation enhanced the sensitivity of RYR1 to activating concentrations of calcium and to caffeine. In parallel, the sensitivity to inhibiting concentrations of calcium and calmodulin was reduced, transferring the mutant calcium-release channel into a hyperexcitable state. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, ARG2458CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933397,
|
|
|
|
|
|
gnomAD: rs28933397,
|
|
|
|
|
|
ClinVar: RCV000013838, RCV000119711, RCV000614410, RCV000796565, RCV001787726, RCV001787727, RCV001787728, RCV001787729, RCV001787730, RCV001787731, RCV001787732, RCV002490361
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In families with malignant hyperthermia susceptibility (MHS1; 145600), Manning et al. (1998) reported 2 novel mutations in the RYR1 gene: a heterozygous c.7372C-T transition, resulting in an arg2458-to-cys (R2458C) substitution, and a heterozygous c.7373G-A transition, resulting in an arg2458-to-his (R2458H; 180901.0009) substitution. Both changes occurred at a CpG dinucleotide in the central region of the RYR1 gene. The R2458C mutation was observed in a Swiss pedigree and in an Italian pedigree; the R2458H mutation was found in a French pedigree. Both mutations segregated with the malignant hyperthermia susceptibility phenotype or the MH equivocal (MHE) phenotype. The authors noted that these mutations represented the most C-terminal mutations in the RYR1 gene reported to that time. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, ARG2458HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918594,
|
|
|
|
|
|
gnomAD: rs121918594,
|
|
|
|
|
|
ClinVar: RCV000013839, RCV000079164, RCV000793289, RCV001787733, RCV001787734, RCV001787735, RCV001787736, RCV001787737, RCV001787738, RCV001787739, RCV004017240
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 180901.0008 and Manning et al. (1998). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, ARG2163CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192175,
|
|
|
|
|
|
gnomAD: rs118192175,
|
|
|
|
|
|
ClinVar: RCV000013840, RCV000056223, RCV000119653, RCV001385701, RCV001787740, RCV001787741, RCV001787742, RCV001787743, RCV001787744, RCV001787745, RCV001787746
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated families (D1 and D2), Manning et al. (1998) demonstrated that members with malignant hyperthermia (MHS1; 145600) had a heterozygous c.6487C-T transition in the RYR1 gene, resulting in an arg2163-to-cys (R2163C) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, ARG2163HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192163,
|
|
|
|
|
|
gnomAD: rs118192163,
|
|
|
|
|
|
ClinVar: RCV000013841, RCV000013842, RCV000119654, RCV001204982, RCV001787747, RCV001787748, RCV001787749, RCV001787750, RCV001787751, RCV001787752, RCV001787753
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian mother and daughter (family It2) with MHS (145600), Manning et al. (1998) identified a heterozygous c.6488G-A transition in the RYR1 gene, resulting in an arg2163-to-cys (R2163C) substitution. The family had been studied by Tegazzin et al. (1994). The proband had undergone 8 previous surgical procedures under general anesthesia before presenting with an MH crisis. On 6 of these previous occasions, an MH-triggering anesthetic had been used. Histologic examination of muscle biopsy from the mother revealed a predominance of type 1 fibers with central cores present in many fibers. Neither she nor her daughter had symptoms of a congenital myopathy. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT, WITH SUSCEPTIBILITY TO MALIGNANT HYPERTHERMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, ILE4898THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192170,
|
|
|
|
|
|
|
|
ClinVar: RCV000013843, RCV000013844, RCV000119552, RCV000535754, RCV000763430, RCV001787754, RCV001787755, RCV001787756, RCV001787757, RCV001787758, RCV001787759, RCV001787760, RCV004586003, RCV004737150
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a large Mexican kindred in which affected members through 4 generations had autosomal dominant congenital myopathy-1A (CMYO1A; 117000) associated with central cores on muscle biopsy, Lynch et al. (1999) identified a heterozygous c.14693T-C transition in the RYR1 gene, resulting in an ile4898-to-thr (I4898T) mutation in the C-terminal transmembrane region of the RYR1 protein. In 2 family members tested, malignant hyperthermia was also present. Lynch et al. (1999) noted that all previously reported RYR1 mutations had been located either in the cytoplasmic N terminus or in a central cytoplasmic region of the protein. Introduction of the I4898T mutation into a rabbit RYR1 cDNA and expression in HEK293 cells resulted in abolition of response to the agonists halothane and caffeine. Coexpression of normal and mutant RYR1 cDNAs in a 1:1 ratio, however, produced RYR1 channels with normal halothane and caffeine sensitivities, but maximal levels of Ca(2+) release were reduced by 67%. Binding of [3H]ryanodine indicated that the heterozygous channel was activated by Ca(2+) concentrations 4-fold lower than normal. Single-cell analysis of cotransfected cells showed a significantly increased resting cytoplasmic Ca(2+) level and a significantly reduced luminal Ca(2+) level. These data indicated a leaky channel, possibly caused by a reduction in the Ca(2+) concentration required for channel activation. Comparison with 2 other coexpressed mutant/normal channels suggested that the I4898T mutation produces one of the most abnormal RYR1 channels that had been investigated, and this level of abnormality was reflected in the severe and penetrant phenotype of the patients with congenital myopathy in the pedigree. </p><p>Tilgen et al. (2001) identified the I4898T mutation, resulting from a c.14693T-C transition, in 3 of 25 unrelated individuals with CMYO1A. The isoleucine residue is highly conserved and is located in the C-terminal hydrophobic membrane-spanning region of the protein. </p><p>In 2 members of a family (CCD05) and an unrelated patient (CCD11) with CMYO1A, Monnier et al. (2001) identified a heterozygous I4898T mutation in exon 102 of the RYR1 gene. </p><p><strong><em>Variant Function</em></strong></p><p>
|
|
Avila et al. (2001) expressed the analogous rabbit mutation (I4897T) in skeletal myotubes derived from Ryr1-knockout mice. They found that homozygous expression of I4897T in myotubes resulted in a complete uncoupling of sarcolemmal excitation from voltage-gated sarcoplasmic reticulum (SR) calcium ion release without significantly altering resting cytosolic calcium ion levels, sarcoplasmic reticulum calcium ion content, or Ryr1-mediated enhancement of dihydropyridine receptor (DHPR) channel activity. Coexpression of both I4897T and wildtype Ryr1 resulted in a 60% reduction in voltage-gated SR calcium ion release, again without altering resting cytosolic calcium ion levels, SR calcium ion content, or DHPR channel activity. These findings indicated that muscle weakness in patients with the I4898T mutation involves a functional uncoupling of sarcolemmal excitation from SR calcium ion release, rather than the expression of overactive or leaky SR calcium ion release channels. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, VAL2168MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192176,
|
|
|
|
|
|
|
|
ClinVar: RCV000013845, RCV000119656, RCV000557804, RCV000578323, RCV001729347, RCV001787761, RCV001787762, RCV001787763, RCV001787764, RCV001787765, RCV001787766, RCV001787767, RCV003398498
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected individuals from 8 Swiss families with malignant hyperthermia (MHS1; 145600), Manning et al. (1998) identified a heterozygous G-to-A change in the RYR1 gene, resulting in a val2168-to-met (V2168M) substitution. </p><p>Monnier et al. (2001) identified a heterozygous V2168M mutation resulting from a c.6502G-A transition in exon 39 of the RYR1 gene in a 52-year-old patient (CCD14) with congenital myopathy-1A (CMYO1A; 117000). She had a history of mild orthopedic problems during infancy, mild proximal muscle weakness, and cores on muscle biopsy. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
KING-DENBOROUGH SYNDROME, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, THR2206MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192177,
|
|
|
|
|
|
gnomAD: rs118192177,
|
|
|
|
|
|
ClinVar: RCV000013846, RCV000119662, RCV000162149, RCV000606881, RCV000655558, RCV001729348, RCV004556715, RCV004658961, RCV005016260
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Malignant Hyperthermia, Susceptibility to, 1</em></strong></p><p>
|
|
In affected members of a family with malignant hyperthermia (MHS1; 145600), Manning et al. (1998) identified a heterozygous c.6617C-T transition in the RYR1 gene, resulting in a thr2206-to-met (T2206M) substitution. </p><p>Wehner et al. (2002) identified the T2206M mutation in patients with MHS. Myotubes derived from individuals with the T2206M mutation had an abnormal response of the intracellular calcium concentration to 4-chloro-m-cresol and to caffeine. In myotubes, the EC50 for 4-chloro-m-cresol and for caffeine was reduced strikingly, indicating that this mutation is pathogenic for malignant hyperthermia. </p><p><strong><em>King-Denborough Syndrome</em></strong></p><p>
|
|
In a 6-year-old boy (patient 1) with King-Denborough syndrome (KDS; 619542), Dowling et al. (2011) identified heterozygosity for the c.6617C-T transition in exon 40 of the RYR1 gene, resulting in a T2206M substitution. The mutation was identified by RYR1 gene sequencing. Western blot analysis in patient muscle tissue showed an 84% reduction in RyR1 protein level compared to control. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, THR4826ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918595,
|
|
|
|
|
|
gnomAD: rs121918595,
|
|
|
|
|
|
ClinVar: RCV000013847, RCV000119520, RCV001787768, RCV001787769, RCV001787770, RCV001787771, RCV001787772, RCV001787773, RCV001787774, RCV003591630
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Brown et al. (2000) reported a large Maori pedigree consisting of 5 probands who experienced clinical episodes of malignant hyperthermia (MHS1; 145600) and 130 members diagnosed by in vitro contracture testing (IVCT). Sequencing of RYR1 cDNA in an affected individual from this pedigree identified a novel heterozygous c.14477C-T transition, resulting in a thr4826-to-ile (T4826I) substitution in the C-terminal region/transmembrane loop of the skeletal muscle ryanodine receptor. This was the first mutation in the RYR1 C-terminal region associated solely with MHS. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT, WITH SUSCEPTIBILITY TO MALIGNANT HYPERTHERMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, TYR4796CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192167,
|
|
|
|
|
|
|
|
ClinVar: RCV000013848, RCV000013849, RCV000119509, RCV001060960, RCV001787775, RCV001787776, RCV001787777, RCV001787778, RCV001787779, RCV001787780, RCV001787781
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 affected members of a 3-generation French family with congenital myopathy-1A (CMYO1A; 117000), Monnier et al. (2000) identified a heterozygous c.14387G-A transition in exon 100 of the RYR1 gene, resulting in a tyr4796-to-cys (Y4796C) substitution in the C-terminal channel-forming domain of the RYR1 protein. Expression of the mutant RYR1 cDNA in rabbit HEK293 cells produced channels with increased caffeine sensitivity, cells with increased resting cytoplasmic Ca(2+) levels, and a significantly reduced maximal level of Ca(2+) release, suggesting an increased rate of Ca(2+) leakage in the mutant channel. The authors hypothesized that the resulting chronic elevation in myoplasmic Ca(2+) concentration may be responsible for the severe phenotype in this family. Haplotype analysis indicated that the mutation arose de novo in the proband. Testing of skeletal muscle from the proband showed susceptibility to malignant hyperthermia. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, GLU2347DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918596,
|
|
|
|
|
|
|
|
ClinVar: RCV000013850, RCV000119679, RCV000171131, RCV001384027, RCV001787979, RCV001787980, RCV001787981, RCV001787982, RCV001787983, RCV001787984, RCV001787985
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 2 unrelated families with malignant hyperthermia (MHS1; 145600), Sambuughin et al. (2001) identified a heterozygous 3-bp deletion (GGA) in exon 44 of the RYR1 gene, resulting in deletion of the conserved glutamic acid at position 2347. The deletion of glu2347 was accompanied by an unusually large electrically evoked contraction tension in the in vitro diagnostic pharmacologic contracture test in MH-positive persons, suggesting that this deletion produces an alteration in skeletal muscle calcium regulation, even in the absence of pharmacologic agents. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, 9-BP DEL, NT12640
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192165,
|
|
|
|
|
|
|
|
ClinVar: RCV000013851, RCV000119463
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a 4-generation family (CCD10) with autosomal dominant congenital myopathy-1A (CMYO1A; 117000), Monnier et al. (2001) identified a heterozygous 9-bp deletion (amino acids 12640-12648, 12640delCGCCAGTTC) in exon 91 of the RYR1 gene, eliminating the codons for arg4214, gln4215, and phe4216 from the transcript. The authors noted that these 3 amino acids are conserved among all 3 human RYR genes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, ARG4861HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs63749869,
|
|
|
|
|
|
|
|
ClinVar: RCV000013852, RCV000119533, RCV000534187, RCV000851296, RCV001787782, RCV001787783, RCV001787784, RCV001787785, RCV001787786, RCV001787787, RCV001787788, RCV004017241, RCV004991972
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Among 7 of 25 unrelated individuals with congenital myopathy-1A (CMYO1A; 117000) with central cores on muscle biopsy, Tilgen et al. (2001) identified a heterozygous c.14582G-A transition in the RYR1 gene, resulting in an arg4861-to-his (R4861H) substitution at a highly conserved residue in the C-terminal region of the protein. </p><p>In affected members of 2 unrelated families (CCD07 and CCD15) and an unrelated patient (CCD09) with CMYO1A, Monnier et al. (2001) identified a heterozygous R4861H mutation in exon 101 of the RYR1 gene. The mutation occurred de novo in patient CCD09. </p><p>Quinlivan et al. (2003) identified a de novo heterozygous R4861H mutation in exon 101 of the RYR1 gene in an 11-year-old boy (family D) with CMYO1A. Functional studies of the variant were not performed. As an infant, he had hypotonia with poor feeding. He later showed delayed motor development, inability to walk independently, congenital hip dislocation, lordosis, and upper limb involvement. </p><p>Sato et al. (2008) identified heterozygosity for the R4861H mutation in a 6-month-old Japanese boy (patient 2) with CMYO1A manifest as 'congenital neuromuscular disease with uniform type 1 fiber' (CNMDU1). He had poor sucking, muscle weakness, joint contractures, and 99.9% type 1 muscle fibers on skeletal muscle biopsy. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-text-font">
|
|
<strong>.0020 MOVED TO 180901.0012</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, PRO3527SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192164,
|
|
|
|
|
|
|
|
ClinVar: RCV000119413, RCV004558247
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a consanguineous Algerian family (family 1) with autosomal recessive congenital myopathy-1B (CMYO1B; 255320) characterized by the presence of multiple, short-length core lesions (minicores) in both muscle fiber types, Ferreiro et al. (2002) identified homozygosity for a c.10579C-T transition in exon 71 of the RYR1 gene that resulted in a pro3527-to-ser (P3527S) substitution. Three children in the family presented in infancy with moderate weakness predominant in axial muscles, pelvic girdle and hands, joint hyperlaxity, hand involvement, and multiple minicores on skeletal muscle biopsy. New muscle biopsies from the 3 patients in adulthood demonstrated central core disease with rods; no cores were found in the healthy parents. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, VAL4849ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192168,
|
|
|
|
|
|
gnomAD: rs118192168,
|
|
|
|
|
|
ClinVar: RCV000013856, RCV000119527, RCV000990211, RCV001060435, RCV001787789, RCV001787790, RCV001787791, RCV001787792, RCV001787793, RCV001787794, RCV001787795, RCV004017242, RCV004586004, RCV004658962, RCV004786258
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 19-year-old girl, born of consanguineous parents (family 1), with autosomal recessive congenital myopathy-1B (CMYO1B; 255320) with both multiminicores and cores on muscle biopsy and confirmed linkage to the RYR1 locus, Jungbluth et al. (2002) identified a homozygous c.14545G-A transition in exon 101 of the RYR1 gene, resulting in a val4849-to-ile (V4849I) substitution. </p><p>In a 9-year-old girl, born of consanguineous parents, with autosomal recessive CMYO1B and central core disease on muscle biopsy, Kossugue et al. (2007) identified a homozygous V4849I substitution in the RYR1 gene. </p><p>Monnier et al. (2008) reported a 9-year-old Dutch boy with a severe autosomal recessive myopathy with ptosis and facial diplegia associated with compound heterozygous mutations in the RYR1 gene: V4849I and a 4-bp insertion (180901.0032). The patient had severe neonatal hypotonia, delayed motor development, amyotrophy, kyphoscoliosis, required ventilatory assistance at age 4 years, and was never able to walk. A sister had died at age 5 years of myopathic respiratory insufficiency. Monnier et al. (2008) postulated that since the patient had a hypomorphic frameshift RYR1 allele, the resultant phenotype was more severe compared to those patients with homozygous V4849I mutations. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, ARG2676TRP AND THR2787SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193922826, rs35180584,
|
|
|
|
|
|
gnomAD: rs193922826, rs35180584,
|
|
|
|
|
|
ClinVar: RCV000013857, RCV000119737, RCV000119746, RCV000147446, RCV000202878, RCV000209984, RCV000335435, RCV000392959, RCV000403812, RCV000817589, RCV001079361, RCV001802876, RCV001802881, RCV002288603, RCV002498553
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with susceptibility to malignant hyperthermia (MHS1; 145600), Guis et al. (2004) identified heterozygosity for 2 mutations in the RYR1 gene on the same allele: an c.8026C-T transition in exon 50, resulting in an arg2676-to-trp (R2676W) substitution, and an c.8160C-G transversion in exon 53, resulting in a thr2787-to-ser (T2787S) substitution. Affected members of the family had an unusual clinical phenotype including multiminicore myopathy without clinical muscle involvement. Guis et al. (2004) suggested that the R2676W mutation is the candidate mutation responsible for MHS and that the T2787S mutation is a 'secondary aggravating' mutation leading to histologic multiminicores. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, 18-BP DEL, NT14588
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192169,
|
|
|
|
|
|
|
|
ClinVar: RCV000013858
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In DNA from a patient with congenital myopathy-1A (CMYO1A; 117000), Zorzato et al. (2003) detected a heterozygous deletion of nucleotides 14588 to 14606 in exon 101 of the RYR1 gene. The deletion was also detected in the patient's mildly affected mother. The deletion was predicted to result in the deletion of 7 amino acids (4863-4869, FYNKSED) and insertion of a novel tyrosine residue in the pore-forming region of the sarcoplasmic reticulum calcium release channel. Heterologous expression of recombinant RYR1 peptides and analysis of their membrane topology demonstrated that the deleted amino acids are localized in the luminal loop connecting membrane-spanning segments M8 and M10. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, 119-BP INS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193922886,
|
|
|
|
|
|
|
|
ClinVar: RCV000013859, RCV000119539
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 17-year-old Tunisian boy, born of first-cousin parents, with congenital myopathy-1B (CMYO1B; 255320) manifest as multiminicore disease with ophthalmoplegia, Monnier et al. (2003) identified a homozygous 119-bp insertion at position 14646 of the RYR1 gene and an A-to-G transition at position +1 from the insertion fragment, resulting in a frameshift of the last 94 amino acids downstream of the insertion site and a premature stop codon. The mutation, designated 14646+2.99 kb A-to-G, resulted in a 90% decrease of the normal RYR1 transcript in skeletal muscle. The mutation was not expressed in lymphoblastoid cells, suggesting a tissue-specific splicing mechanism. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, ARG109TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192173,
|
|
|
|
|
|
gnomAD: rs118192173,
|
|
|
|
|
|
ClinVar: RCV000013860, RCV000119608, RCV000655512, RCV001199051, RCV003447473, RCV003996093, RCV004586005, RCV005003354
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs with congenital myopathy-1B (CMYO1B; 255320) manifest as minicore myopathy with external ophthalmoplegia, Jungbluth et al. (2005) identified a c.325C-T transition in exon 4 of the RYR1 gene, resulting in an arg109-to-trp (R109W) substitution in a highly conserved region. Analysis of cDNA showed homozygosity for the mutation, but genomic DNA showed heterozygosity. Jungbluth et al. (2005) postulated that the second allele was either not expressed or deleted and may indicate a promoter mutation or a large deletion. Haplotype analysis and the unaffected parental carrier status were consistent with biallelic mutations and autosomal recessive inheritance. </p><p>Klein et al. (2012) reanalyzed one of these patients as patient 41 and identified an additional missense and nonsense mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, MET2423LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192174,
|
|
|
|
|
|
gnomAD: rs118192174,
|
|
|
|
|
|
ClinVar: RCV000013861, RCV000119694, RCV000415169, RCV001197410, RCV001851835, RCV002504782, RCV003996094, RCV004017243, RCV004813035
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 sibs with congenital myopathy-1B (CMYO1B; 255320) manifest as minicore myopathy with external ophthalmoplegia originally reported by Swash and Schwartz (1981), Jungbluth et al. (2005) identified a c.7268T-A transversion in exon 45 the RYR1 gene, resulting in a met2423-to-lys substitution in a highly conserved region. Analysis of cDNA showed homozygosity for the mutation, but genomic DNA showed heterozygosity. Jungbluth et al. (2005) postulated that the second allele was either not expressed or deleted and may indicate a promoter mutation or a large deletion. Haplotype analysis and the unaffected parental carrier status were consistent with biallelic mutations and autosomal recessive inheritance. </p><p>Klein et al. (2012) reanalyzed one of these patients as patient 44 and identified a W661X mutation in trans with the M2423 allele. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, IVS99AS, A-T, -2
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193922870,
|
|
|
|
|
|
|
|
ClinVar: RCV000013862, RCV000119507
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs (family 5) with congenital myopathy-1B (CMYO1B; 255320) manifest as minicore myopathy with external ophthalmoplegia, Jungbluth et al. (2005) identified compound heterozygosity for 2 mutations in the RYR1 gene: an A-to-T transversion in intron 99 (c.14365-2A-T), resulting in a splice site mutation, and a c.10349C-T transition in exon 68, resulting in a ser3450-to-phe (S3450F) substitution (180901.0029). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, SER3450PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193922836,
|
|
|
|
|
|
|
|
ClinVar: RCV000013863, RCV000119408, RCV003996095
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the ser3450-to-phe (S3450F) mutation in the RYR1 gene that was found in 2 sibs with congenital myopathy-1B (CMYO1B; 255320) by Jungbluth et al. (2005), see 180901.0028. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, THR4637ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192166,
|
|
|
|
|
|
|
|
ClinVar: RCV000013864, RCV000119487, RCV001824568, RCV001851836
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a large family with autosomal dominant congenital myopathy-1A (CMYO1A; 117000), Scacheri et al. (2000) identified a heterozygous c.13996A-G transition in exon 95 of the RYR1 gene, resulting in a thr4637-to-ala (T4637A) substitution within the transmembrane domain. Skeletal muscle biopsies from 2 affected individuals showed the presence of central cores in over 85% of myofibers and nemaline rods in 5 to 25% of myofibers. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, TYR522SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192162,
|
|
|
|
|
|
|
|
ClinVar: RCV000013865, RCV000119574, RCV001787796, RCV001787797, RCV001787798, RCV001787799, RCV001787800, RCV001787801, RCV001787802
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a French family with malignant hyperthermia (MHS1; 145600), Quane et al. (1994) identified a heterozygous c.1565A-C transversion in the RYR1 gene, resulting in a tyr522-to-ser (Y522S) substitution. Skeletal muscle biopsies from 2 patients in this family showed central cores in the absence of clinical features of a myopathy. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0032 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, 4-BP INS, 1742ATCA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193922771,
|
|
|
|
|
|
|
|
ClinVar: RCV000013867, RCV000119584, RCV003591631
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 9-year-old Dutch boy with a severe form of autosomal recessive congenital myopathy-1B (CMYO1B; 255320), Monnier et al. (2008) detected compound heterozygous mutations in the RYR1 gene: V4849I (180901.0022) and a 4-bp insertion (c.1742insATCA). The patient had severe neonatal hypotonia, delayed motor development, amyotrophy, kyphoscoliosis, required ventilatory assistance at age 4 years, and was never able to walk. A sister had died at age 5 years of myopathic respiratory insufficiency. The 4-bp insertion was predicted to result in a premature stop codon and an unstable truncated protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0033 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, 2-BP DEL/2-BP INS, NT14761
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192171,
|
|
|
|
|
|
|
|
ClinVar: RCV000013868, RCV000119559, RCV002513027
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 11-year-old Japanese patient with congenital myopathy-1A (CMYO1A; 117000), Sato et al. (2008) identified a heterozygous 2-bp deletion/2-bp insertion (c.14761delTTinsAC) in exon 102 of the RYR1 gene, resulting in a phe4921-to-thr (F4921T) substitution. The patient had delayed motor milestones, proximal muscle weakness, and uniform type 1 fibers on muscle biopsy. The patient's affected father, who carried the same mutation (Wu et al., 2006), showed typical central cores on muscle biopsy. The family had previously been reported by Tojo et al. (2000). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0034 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, 20-BP DEL, NT13013
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193922856,
|
|
|
|
|
|
|
|
ClinVar: RCV000013870, RCV000119472, RCV001216605, RCV002288489, RCV004737151
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 8-year-old Japanese patient (P1) with congenital myopathy-1A (CMYO1A; 117000), Sato et al. (2008) identified a heterozygous 20-bp deletion beginning in exon 91 of the RYR1 gene and predicted to result in premature termination and removal of 464 residues from the C terminus of the protein (Ala4338fs). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0035 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, 2-BP DEL, 5726AG AND MET3081THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs147012990, rs387906681,
|
|
|
|
|
|
gnomAD: rs147012990,
|
|
|
|
|
|
ClinVar: RCV000022757, RCV000210003, RCV000253393, RCV000300656, RCV000357829, RCV000404978, RCV000721732, RCV001086670
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 South African patient (patient 1) with a severe form of autosomal recessive congenital myopathy-1B (CMYO1B; 255320), Wilmshurst et al. (2010) identified compound heterozygosity for 2 alleles containing complex mutations in the RYR1 gene: 1 allele carried a 2-bp deletion (5726delAG) in exon 35 and a 9242T-C transition in exon 63, resulting in a met3081-to-thr (M3081T) substitution, and the other allele carried a splice site mutation and a V4842M substitution (180901.0036). The 2-bp del/M3081T allele was also found in patient 12, also South African, in whom a mutation on the second allele was not identified. Haplotype analysis indicated a founder effect in the South African population. The phenotype was characterized by onset at birth, neonatal hypotonia and weakness, delayed motor development, external ophthalmoplegia, and bulbar involvement. Histopathologic findings included central nuclei, multiple internalized nuclei, type 1 fiber predominance and hypotrophy, relative type 2 hypertrophy, and oxidative abnormalities in electron microscopic analysis, although frank cores were not typically seen. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0036 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, IVS68AS, C-G, -6 AND VAL4842MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193922837, rs193922879,
|
|
|
|
|
|
gnomAD: rs193922837, rs193922879,
|
|
|
|
|
|
ClinVar: RCV000022758, RCV000119410, RCV000119524, RCV000148830, RCV000226744, RCV000535801, RCV000546614, RCV000616859, RCV000624604, RCV001132276, RCV001249074, RCV001588937, RCV001775081, RCV002247501, RCV002498549, RCV003997313, RCV004586556, RCV004586558, RCV004689614, RCV005003479
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 11 South African patients with a severe form of autosomal recessive congenital myopathy-1B (CMYO1B; 255320), Wilmshurst et al. (2010) found a common complex allele containing 2 mutations in the RYR1 gene: a C-to-G transversion in intron 68 (10348-6C-G) and a 14524G-A transition in exon 101, resulting in a val4842-to-met (V4842M) substitution. The splice site mutation results in the production of an aberrant transcript that includes intron 68 and introduces a premature stop codon (His3449ins33fsTer54), but penetrance of this mutation is incomplete, resulting in the expression of both spliced and unspliced transcripts (Monnier et al., 2008). Wilmshurst et al. (2010) hypothesized that this allele determines the phenotype by 2 interrelated mechanisms: by reducing the amount of the RYR1 protein and by the V4842M substitution on residual protein. Haplotype analysis indicated a founder effect in the South African population, but Monnier et al. (2008) also found it in 2 sibs from Chile with severe neonatal hypotonia. All except 1 of the 11 patients were compound heterozygous for this allele and another pathogenic allele affecting the RYR1 gene (see, e.g., 180901.0035 and 180901.0037). The phenotype was characterized by onset at birth, neonatal hypotonia and weakness, delayed motor development, external ophthalmoplegia, and bulbar involvement. Histopathologic findings included central nuclei, multiple internalized nuclei, type 1 fiber predominance and hypotrophy, relative type 2 hypertrophy, and oxidative abnormalities in electron microscopic analysis, although frank cores were not typically seen. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0037 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, 2-BP DEL, 8342TA AND HIS3981TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs148772854, rs758580075,
|
|
|
|
|
|
gnomAD: rs148772854, rs758580075,
|
|
|
|
|
|
ClinVar: RCV000022759, RCV000079122, RCV000327345, RCV000333023, RCV000389868, RCV000515090, RCV000721705, RCV001081494, RCV001209505, RCV002535011, RCV003388645, RCV003514405, RCV004586901, RCV005004388
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 South African patients with a severe form of autosomal recessive congenital myopathy-1B (CMYO1B; 255320), Wilmshurst et al. (2010) identified compound heterozygosity for 2 alleles containing complex mutations in the RYR1 gene: 1 allele carried a 2-bp deletion in exon 53 (8342delTA) and a 11941C-T transition in exon 87, resulting in a his3981-to-tyr (H3981Y) substitution, and the other allele carried a splice site mutation and a V4842M substitution (180901.0036). Haplotype analysis indicated a founder effect in the South African population. The phenotype was characterized by onset at birth, neonatal hypotonia and weakness, delayed motor development, external ophthalmoplegia, and bulbar involvement. Histopathologic findings included central nuclei, multiple internalized nuclei, type 1 fiber predominance and hypotrophy, relative type 2 hypertrophy, and oxidative abnormalities in electron microscopic analysis, although frank cores were not typically seen. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0038 KING-DENBOROUGH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, LYS33GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193922746,
|
|
|
|
|
|
|
|
ClinVar: RCV000049252, RCV000119774, RCV001588881, RCV003591651
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 27-year-old woman with King-Denborough syndrome (KDS; 619542), D'Arcy et al. (2008) identified a heterozygous c.97A-G transition in exon 2 of the RYR1 gene, resulting in a lys33-to-glu (K33E) substitution at a highly conserved residue. The mutation was not present in other family members or in 200 normal controls. She was born at term after a pregnancy complicated by decreased fetal movements and breech presentation. At birth, she was noted to have hypotonia, ptosis, high-arched palate, prominent philtrum, and scaphocephaly. The father and paternal grandfather had congenital ptosis, but no other signs of neuromuscular disease. She underwent surgery for ptosis at ages 2 and 9 years without complications. Facial and proximal limb weakness became more apparent with age, and she developed kyphoscoliosis, myopathic facies with flat midface, prominent columella, and webbed neck. An EMG was myopathic and serum creatine kinase was increased. At age 15 years, she developed hyperthermia during surgery for scoliosis repair, and subsequent muscle testing confirmed susceptibility to malignant hyperthermia. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0039 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, ARG2241TER ({dbSNP rs200563280})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs200563280,
|
|
|
|
|
|
gnomAD: rs200563280,
|
|
|
|
|
|
ClinVar: RCV000147436, RCV000148787, RCV000171129, RCV000178453, RCV000263175, RCV000525302, RCV001257398, RCV001530191, RCV002505131
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 6 fetuses, conceived by consanguineous Dutch parents, with congenital myopathy-1B (CMYO1B; 255320) presenting as lethal fetal akinesia, McKie et al. (2014) identified a homozygous c.6721C-T transition (c.6721C-T, NM_000540.2) in the RYR1 gene, resulting in an arg2241-to-ter (R2241X) substitution. The mutation, which was found by homozygosity mapping and candidate gene sequencing, segregated with the disorder in the family. A heterozygous c.6721C-T transition (rs200563280) had been found in 1 of 6,503 genotypes in the Exome Variant Server database. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0040 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, 27-BP DEL, NT2097
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs876661306,
|
|
|
|
|
|
|
|
ClinVar: RCV000171130
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 fetuses, conceived by consanguineous Pakistani parents, with congenital myopathy-1B (CMYO1B; 255320) presenting as lethal fetal akinesia, McKie et al. (2014) identified a homozygous 27-bp deletion (c.2097_2123del, NM_000540.2) in the RYR1 gene that removes 9 conserved amino acids from the SPRY2 domain and replaces glu699 with asp (glu699_gly707del). Each unaffected parent was heterozygous for the mutation. The family was 1 of 36 with a similar lethal phenotype who underwent direct sequencing of the RYR1 gene. Functional studies of the variant were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0041 CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, 3-BP DEL, 7043GAG ({dbSNP rs121918596})
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000013850, RCV000119679, RCV000171131, RCV001384027, RCV001787979, RCV001787980, RCV001787981, RCV001787982, RCV001787983, RCV001787984, RCV001787985
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 fetuses, conceived of consanguineous Palestinian parents, with congenital myopathy-1B (CMYO1B; 255320) presenting as lethal fetal akinesia, McKie et al. (2014) identified a homozygous 3-bp deletion (c.7043_7045delGAG, NM_000540.2) in the RYR1 gene, resulting in the deletion of the conserved residue glu2347 (E2347del). Each unaffected parent was heterozygous for the mutation. The family was 1 of 36 with a similar phenotype who underwent direct sequencing of the RYR1 gene. Functional studies of the variant were not performed. A different 3-bp deletion results in the deletion of the same residue (180901.0017). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0042 KING-DENBOROUGH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, ARG2452TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192124,
|
|
|
|
|
|
|
|
ClinVar: RCV000056226, RCV000119706, RCV000527240, RCV001729374, RCV001787847, RCV001787848, RCV001787849, RCV001787850, RCV001787851, RCV001787852, RCV001787853, RCV002221195, RCV002281899
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 14-year-old proband (patient 2) with King-Denborough syndrome (KDS; 619542), Dowling et al. (2011) identified heterozygosity for a c.7354C-T transition in exon 46 of the RYR1 gene, resulting in an arg2452-to-trp (R2452W) substitution at a highly conserved residue. The mutation, which was found by RYR1 gene sequencing, was also identified in the boy's symptomatic mother and sib. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0043 KING-DENBOROUGH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, ARG2508CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192178,
|
|
|
|
|
|
|
|
ClinVar: RCV000056228, RCV000119718, RCV000552166, RCV000624571, RCV001198416, RCV001731347, RCV001814037, RCV002281900
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-year-old boy with King-Denborough syndrome (KDS; 619542), Joseph et al. (2017) identified heterozygosity for an c.7522C-T transition in the RYR1 gene, resulting in an arg2508-to-cys (R2508C) substitution. The mutation was identified by RYR1 gene sequencing. Functional studies were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0044 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, ARG4893TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192150,
|
|
|
|
|
|
|
|
ClinVar: RCV000056236, RCV000119545, RCV001046476, RCV002496742, RCV003996489
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 2 unrelated families (CCD04 and CCD08) with autosomal dominant congenital myopathy-1A (CMYO1A; 117000), Monnier et al. (2001) identified a heterozygous c.14677C-T transition in exon 102 of the RYR1 gene, resulting in an arg4893-to-trp (R4893W) substitution in the C-terminal domain. </p><p>In 3 members of a 2-generation Asian family (family B) with CMYO1A, Quinlivan et al. (2003) identified a heterozygous R4893W mutation in the RYR1 gene. The mutation occurred in region 3 in the C terminus. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0045 CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
RYR1, TYR4864CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118192146,
|
|
|
|
|
|
|
|
ClinVar: RCV000056251, RCV000119535
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 affected individuals from a 2-generation family (family C) with autosomal dominant congenital myopathy-1A (CMYO1A; 117000), Quinlivan et al. (2003) identified a heterozygous mutation in the RYR1 gene, resulting in a tyr4864-to-cys (R4864C) substitution in exon 102. The mutation occurred in region 3 in the C terminus. Of note, a 44-year-old male family member who carried the mutation was unaffected, suggesting incomplete penetrance, although he had a son with a congenital foot deformity who was not studied. Functional studies of the variant were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Fagerlund et al. (1996); Fagerlund et al. (1992); Levitt et al.
|
|
(1991)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Adeokun, A. M., West, S. P., Ellis, F. R., Halsall, P. J., Hopkins, P. M., Foroughmand, A. M., Iles, D. E., Robinson, R. L., Stewart, A. D., Curran, J. L.
|
|
<strong>The G1021A substitution in the RYR1 gene does not cosegregate with malignant hyperthermia susceptibility in a British pedigree.</strong>
|
|
Am. J. Hum. Genet. 60: 833-341, 1997.
|
|
|
|
|
|
[PubMed: 9106529]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Alestrom, A., Fagerlund, T. H., Berg, K.
|
|
<strong>A simple method to detect the RYR1 mutation G1021A, a cause of malignant hyperthermia susceptibility.</strong>
|
|
Clin. Genet. 47: 274-275, 1995.
|
|
|
|
|
|
[PubMed: 7554356]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1995.tb04311.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Avila, G., O'Brien, J. J., Dirksen, R. T.
|
|
<strong>Excitation-contraction uncoupling by a human central core disease mutation in the ryanodine receptor.</strong>
|
|
Proc. Nat. Acad. Sci. 98: 4215-4220, 2001.
|
|
|
|
|
|
[PubMed: 11274444]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.071048198]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Barone, V., Bertocchini, F., Bottinelli, R., Protasi, F., Allen, P. D., Armstrong, C. F., Reggiani, C., Sorrentino, V.
|
|
<strong>Contractile impairment and structural alterations of skeletal muscles from knockout mice lacking type 1 and type 3 ryanodine receptors.</strong>
|
|
FEBS Lett. 422: 160-164, 1998.
|
|
|
|
|
|
[PubMed: 9489997]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0014-5793(98)00003-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bellinger, A. M., Reiken, S., Carlson, C., Mongillo, M., Liu, X., Rothman, L., Matecki, S., Lacampagne, A., Marks, A. R.
|
|
<strong>Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle.</strong>
|
|
Nature Med. 15: 325-330, 2009.
|
|
|
|
|
|
[PubMed: 19198614]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm.1916]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Benkusky, N. A., Farrell, E. F., Valdivia, H. H.
|
|
<strong>Ryanodine receptor channelopathies.</strong>
|
|
Biochem. Biophys. Res. Commun. 322: 1280-1285, 2004.
|
|
|
|
|
|
[PubMed: 15336975]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.bbrc.2004.08.033]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brandt, A., Schleithoff, L., Jurkat-Rott, K., Klingler, W., Baur, C., Lehmann-Horn, F.
|
|
<strong>Screening of ryanodine receptor gene in 105 malignant hyperthermia families: novel mutations and concordance with the in vitro contracture test.</strong>
|
|
Hum. Molec. Genet. 8: 2055-2062, 1999.
|
|
|
|
|
|
[PubMed: 10484775]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/8.11.2055]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brennan, S., Garcia-Castaneda, M., Michelucci, A., Sabha, N., Malik, S., Groom, L., LaPierre, L. W., Dowling, J. J., Dirksen, R. T.
|
|
<strong>Mouse model of severe recessive RYR1-related myopathy.</strong>
|
|
Hum. Molec. Genet. 28: 3024-3036, 2019.
|
|
|
|
|
|
[PubMed: 31107960]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddz105]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brown, R. L., Pollock, A. N., Couchman, K. G., Hodges, M., Hutchinson, D. O., Waaka, R., Lynch, P., McCarthy, T. V., Stowell, K. M.
|
|
<strong>A novel ryanodine receptor mutation and genotype-phenotype correlation in a large malignant hyperthermia New Zealand Maori pedigree.</strong>
|
|
Hum. Molec. Genet. 9: 1515-1524, 2000.
|
|
|
|
|
|
[PubMed: 10888602]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/9.10.1515]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cavanna, J. S., Greenfield, A. J., Johnson, K. J., Marks, A. R., Nadal-Ginard, B., Brown, S. D. M.
|
|
<strong>Establishment of the mouse chromosome 7 region with homology to the myotonic dystrophy region of human chromosome 19q.</strong>
|
|
Genomics 7: 12-18, 1990.
|
|
|
|
|
|
[PubMed: 1970795]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(90)90513-t]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chelu, M. G., Goonasekera, S. A., Durham, W. J., Tang, W., Lueck, J. D., Riehl, J., Pessah, I. N., Zhang, P., Bhattacharjee, M. B., Dirksen, R. T., Hamilton, S. L.
|
|
<strong>Heat- and anesthesia-induced malignant hyperthermia in an RyR1 knock-in mouse.</strong>
|
|
FASEB J. 20: 329-330, 2006.
|
|
|
|
|
|
[PubMed: 16284304]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1096/fj.05-4497fje]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cheng, H., Lederer, W. J., Cannell, M. B.
|
|
<strong>Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle.</strong>
|
|
Science 262: 740-744, 1993.
|
|
|
|
|
|
[PubMed: 8235594]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.8235594]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
D'Arcy, C. E., Bjorksten, A., Yiu, E. M., Bankier, A., Gillies, R., McLean, C. A., Shield, L. K., Ryan, M. M.
|
|
<strong>King-Denborough syndrome caused by a novel mutation in the ryanodine receptor gene.</strong>
|
|
Neurology 71: 776-777, 2008.
|
|
|
|
|
|
[PubMed: 18765655]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000324929.33780.2f]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Deufel, T., Sudbrak, R., Feist, Y., Rubsam, B., Du Chesne, I., Schafer, K.-L., Roewer, N., Grimm, T., Lehmann-Horn, F., Hartung, E. J., Muller, C. R.
|
|
<strong>Discordance, in a malignant hyperthermia pedigree, between in vitro contracture-test phenotypes and haplotypes for the MHS1 region on chromosome 19q12-13.2, comprising the C1840T transition in the RYR1 gene.</strong>
|
|
Am. J. Hum. Genet. 56: 1334-1342, 1995. Note: Erratum: Am. J. Hum. Genet. 57: 520 only, 1995.
|
|
|
|
|
|
[PubMed: 7762556]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dowling, J. J., Lillis S., Amburgey, K., Zhou, H., Al-Sarraj, S., Buk, S. J. A., Wraige, E., Chow, G., Abbs, S., Leber, S., Lachlan, K., Baralle, D., Taylor, A., Sewry, C., Muntoni, F., Jungbluth, H.
|
|
<strong>King-Denborough syndrome with and without mutations in the skeletal muscle ryanodine receptor (RYR1) gene.</strong>
|
|
Neuromusc. Disord. 21: 420-427, 2011.
|
|
|
|
|
|
[PubMed: 21514828]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.nmd.2011.03.006]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ducreux, S., Zorzato, F., Muller, C., Sewry, C., Muntoni, F., Quinlivan, R., Restagno, G., Girard, T., Treves, S.
|
|
<strong>Effect of ryanodine receptor mutations on interleukin-6 release and intracellular calcium homeostasis in human myotubes from malignant hyperthermia-susceptible individuals and patients affected by central core disease.</strong>
|
|
J. Biol. Chem. 279: 43838-43846, 2004.
|
|
|
|
|
|
[PubMed: 15299003]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M403612200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Durham, W. J., Aracena-Parks, P., Long, C., Rossi, A. E., Goonasekera, S. A., Boncompagni, S., Galvan, D. L., Gilman, C. P., Baker, M. R., Shirokova, N., Protasi, F., Dirksen, R., Hamilton, S. L.
|
|
<strong>RyR1 S-nitrosylation underlies environmental heat stroke and sudden death in Y522S RyR1 knockin mice.</strong>
|
|
Cell 133: 53-65, 2008.
|
|
|
|
|
|
[PubMed: 18394989]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2008.02.042]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Efremov, R. G., Leitner, A., Aebersold, R., Raunser, S.
|
|
<strong>Architecture and conformational switch mechanism of the ryanodine receptor.</strong>
|
|
Nature 517: 39-43, 2015.
|
|
|
|
|
|
[PubMed: 25470059]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature13916]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Elbaz, M., Ruiz, A., Bachmann, C., Eckhardt, J., Pelczar, P., Venturi, E., Lindsay, C., Wilson, A. D., Alhussni, A., Humberstone, T., Pietrangelo, L., Boncompagni, S., Sitsapesan, R., Treves, S., Zorzato, F.
|
|
<strong>Quantitative RyR1 reduction and loss of calcium sensitivity of RyR1Q1970fsX16+A4329D cause cores and loss of muscle strength.</strong>
|
|
Hum. Molec. Genet. 28: 2987-2999, 2019.
|
|
|
|
|
|
[PubMed: 31044239]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddz092]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Elbaz, M., Ruiz, A., Eckhardt, J., Pelczar, O., Muntoni, F. Boncompagni, S., Treves, S., Zorzato, F.
|
|
<strong>Quantitative reduction of RyR1 protein caused by a single-allele frameshift mutation in RYR1 ex36 impairs the strength of adult skeletal muscle fibres.</strong>
|
|
Hum. Molec. Genet. 28: 1872-1884, 2019.
|
|
|
|
|
|
[PubMed: 30689883]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddz025]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eu, J. P., Sun, J., Xu, L., Stamler, J. S., Meissner, G.
|
|
<strong>The skeletal muscle calcium release channel: coupled O2 sensor and NO signaling functions.</strong>
|
|
Cell 102: 499-509, 2000.
|
|
|
|
|
|
[PubMed: 10966111]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)00054-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fagerlund, T. H., Islander, G., Ranklev-Twetman, E., Berg, K.
|
|
<strong>Recombination between the postulated CCD/MHE/MHS locus and RYR1 gene markers.</strong>
|
|
Clin. Genet. 50: 455-458, 1996.
|
|
|
|
|
|
[PubMed: 9147872]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1996.tb02711.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fagerlund, T. H., Islander, G., Twetman, E. R., Berg, K.
|
|
<strong>A search for three known RYR1 gene mutations in 41 Swedish families with predisposition to malignant hyperthermia.</strong>
|
|
Clin. Genet. 48: 12-16, 1995.
|
|
|
|
|
|
[PubMed: 7586638]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1995.tb04047.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fagerlund, T. H., Ording, H., Bendixen, D., Islander, G., Ranklev Twetman, E., Berg, K.
|
|
<strong>Discordance between malignant hyperthermia susceptibility and RYR1 mutation C1840T in two Scandinavian MH families exhibiting this mutation.</strong>
|
|
Clin. Genet. 52: 416-421, 1997.
|
|
|
|
|
|
[PubMed: 9520251]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1997.tb02561.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fagerlund, T., Islander, G., Ranklev, E., Harbitz, I., Hauge, J. G., Mokleby, E., Berg, K.
|
|
<strong>Genetic recombination between malignant hyperthermia and calcium release channel in skeletal muscle.</strong>
|
|
Clin. Genet. 41: 270-272, 1992.
|
|
|
|
|
|
[PubMed: 1318804]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fagerlund, T., Ording, H., Bendixen, D., Berg, K.
|
|
<strong>Search for three known mutations in the RYR gene in 48 Danish families with malignant hyperthermia.</strong>
|
|
Clin. Genet. 46: 401-404, 1994.
|
|
|
|
|
|
[PubMed: 7889656]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1994.tb04406.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fagerlund, T., Ording, H., Bendixen, D., Islander, G., Ranklev-Twetman, E., Berg, K.
|
|
<strong>RYR1 mutation G1021A (gly341-to-arg) is not frequent in Danish and Swedish families with malignant hyperthermia susceptibility.</strong>
|
|
Clin. Genet. 49: 186-188, 1996.
|
|
|
|
|
|
[PubMed: 8828983]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1996.tb03284.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ferreiro, A., Monnier, N., Romero, N. B., Leroy, J.-P., Bonnemann, C., Haenggeli, C.-A., Straub, V., Voss, W. D., Nivoche, Y., Jungbluth, H., Lemainque, A., Voit, T., Lunardi, J., Fardeau, M., Guicheney, P.
|
|
<strong>A recessive form of central core disease, transiently presenting as multi-minicore disease, is associated with a homozygous mutation in the ryanodine receptor type 1 gene.</strong>
|
|
Ann. Neurol. 51: 750-759, 2002.
|
|
|
|
|
|
[PubMed: 12112081]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.10231]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fujii, J., Otsu, K., Zorzato, F., de Leon, S., Khanna, V. K., Weiler, J. E., O'Brien, P. J., MacLennan, D. H.
|
|
<strong>Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia.</strong>
|
|
Science 253: 448-451, 1991.
|
|
|
|
|
|
[PubMed: 1862346]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1862346]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gillard, E. F., Otsu, K., Fujii, J., Duff, C., de Leon, S., Khanna, V. K., Britt, B. A., Worton, R. G., MacLennan, D. H.
|
|
<strong>Polymorphisms and deduced amino acid substitutions in the coding sequence of the ryanodine receptor (RYR1) gene in individuals with malignant hyperthermia.</strong>
|
|
Genomics 13: 1247-1254, 1992.
|
|
|
|
|
|
[PubMed: 1354642]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(92)90042-q]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gillard, E. F., Otsu, K., Fujii, J., Khanna, V. K., de Leon, S., Derdemezi, J., Britt, B. A., Duff, C. L., Worton, R. G., MacLennan, D. H.
|
|
<strong>A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia.</strong>
|
|
Genomics 11: 751-755, 1991.
|
|
|
|
|
|
[PubMed: 1774074]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(91)90084-r]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Girard, T., Urwyler, A., Censier, K., Mueller, C. R., Zorzato, F., Treves, S.
|
|
<strong>Genotype-phenotype comparison of the Swiss malignant hyperthermia population.</strong>
|
|
Hum. Mutat. 18: 357-358, 2001.
|
|
|
|
|
|
[PubMed: 11668625]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1203]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Guis, S., Figarella-Branger, D., Monnier, N., Bendahan, D., Kozak-Ribbens, G., Mattei, J.-P., Lunardi, J., Cozzone, P. J., Pellissier, J.-F.
|
|
<strong>Multiminicore disease in a family susceptible to malignant hyperthermia: histology, in vitro contracture tests, and genetic characterization.</strong>
|
|
Arch. Neurol. 61: 106-113, 2004.
|
|
|
|
|
|
[PubMed: 14732627]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archneur.61.1.106]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hall-Curran, J. L., Stewart, A. D., Ball, S. P., Halsall, J. P., Hopkins, P. M., Ellis, F. R.
|
|
<strong>No C1840 to T mutation in RYR1 in malignant hyperthermia. (Letter)</strong>
|
|
Hum. Mutat. 2: 330, 1993.
|
|
|
|
|
|
[PubMed: 8401544]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380020418]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Harbitz, I., Chowdhary, B., Thomsen, P. D., Davies, W., Kaufmann, U., Kran, S., Gustavsson, I., Christensen, K., Hauge, J. G.
|
|
<strong>Assignment of the porcine calcium release channel gene, a candidate for the malignant hyperthermia locus, to the 6p11-q21 segment of chromosome 6.</strong>
|
|
Genomics 8: 243-248, 1990.
|
|
|
|
|
|
[PubMed: 2174405]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(90)90278-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Harbitz, I., Kristensen, T., Bosnes, M., Kran, S., Davies, W.
|
|
<strong>DNA sequence of the skeletal muscle calcium release channel cDNA and verification of the arg615-to-cys615 mutation, associated with porcine malignant hyperthermia, in Norwegian Landrace pigs.</strong>
|
|
Animal Genet. 23: 395-402, 1992.
|
|
|
|
|
|
[PubMed: 1329581]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2052.1992.tb02157.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johnston, J. J., Dirksen, R. T., Girard, T., Gonsalves, S. G., Hopkins, P. M., Riazi, S., Saddic, L. A., Sambuughin, N., Saxena, R., Stowell, K., Weber, J., Rosenberg, H., Biesecker, L. G.
|
|
<strong>Variant curation expert panel recommendations for RYR1 pathogenicity classifications in malignant hyperthermia susceptibility.</strong>
|
|
Genet. Med. 23: 1288-1295, 2021.
|
|
|
|
|
|
[PubMed: 33767344]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41436-021-01125-w]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Joseph, M. R., Theroux, M. C., Mooney, J. J., Falitz, S., Brandom, B. W., Byler, D. L.
|
|
<strong>Intraoperative presentation of malignant hyperthermia (confirmed by RYR1 gene mutation, c.7522C-T; p.R2508C) leads to diagnosis of King-Denborough syndrome in a child with hypotonia and dysmorphic features: a case report.</strong>
|
|
A. A. Case Rep. 8: 55-57, 2017.
|
|
|
|
|
|
[PubMed: 27918309]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1213/XAA.0000000000000421]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jungbluth, H., Muller, C. R., Halliger-Keller, B., Brockington, M., Brown, S. C., Feng, L., Chattopadhyay, A., Mercuri, E., Manzur, A. Y., Ferreiro, A., Laing, N. G., Davis, M. R., Roper, H. P., Dubowitz, V., Bydder, G., Sewry, C. A., Muntoni, F.
|
|
<strong>Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores.</strong>
|
|
Neurology 59: 284-287, 2002.
|
|
|
|
|
|
[PubMed: 12136074]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.59.2.284]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jungbluth, H., Zhou, H., Hartley, L., Halliger-Keller, B., Messina, S., Longman, C., Brockington, M., Robb, S. A., Straub, V., Voit, T., Swash, M., Ferreiro, A., Bydder, G., Sewry, C. A., Muller, C., Muntoni, F.
|
|
<strong>Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene.</strong>
|
|
Neurology 65: 1930-1935, 2005.
|
|
|
|
|
|
[PubMed: 16380615]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000188870.37076.f2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Keating, K. E., Quane, K. A., Manning, B. M., Lehane, M., Hartung, E., Censier, K., Urwyler, A., Klausnitzer, M., Muller, C. R., Heffron, J. J. A., McCarthy, T. V.
|
|
<strong>Detection of a novel RYR1 mutation in four malignant hyperthermia pedigrees.</strong>
|
|
Hum. Molec. Genet. 3: 1855-1858, 1994.
|
|
|
|
|
|
[PubMed: 7849712]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/3.10.1855]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Klein, A., Lillis, S., Munteanu, I., Scoto, M., Zhou, H., Quinlivan, R., Straub, V., Manzur, A. Y., Roper, H., Jeannet, P-Y., Rakowicz, W., Jones, D. H., and 20 others.
|
|
<strong>Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies.</strong>
|
|
Hum. Mutat. 33: 981-988, 2012. Note: Erratum: Hum. Mutat. 33: 1310, 2012.
|
|
|
|
|
|
[PubMed: 22473935]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.22056]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kossugue, P. M., Paim, J. F., Navarro, M. M., Silva, H. C., Pavanello, R. C. M., Gurgel-Giannetti, J., Zatz, M., Vainzof, M.
|
|
<strong>Central core disease due to recessive mutations in RYR1 gene: is it more common than described?</strong>
|
|
Muscle Nerve 35: 670-674, 2007.
|
|
|
|
|
|
[PubMed: 17226826]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/mus.20715]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Levitt, R. C., Nouri, N., Jedlicka, A. E., McKusick, V. A., Marks, A. R., Shutack, J. G., Fletcher, J. E., Rosenberg, H., Meyers, D. A.
|
|
<strong>Evidence for genetic heterogeneity in malignant hyperthermia susceptibility.</strong>
|
|
Genomics 11: 543-547, 1991.
|
|
|
|
|
|
[PubMed: 1774061]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(91)90061-i]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lyfenko, A. D., Goonasekera, S. A., Dirksen, R. T.
|
|
<strong>Dynamic alterations in myoplasmic Ca(2+) in malignant hyperthermia and central core disease.</strong>
|
|
Biochem. Biophys. Res. Commun. 322: 1256-1266, 2004.
|
|
|
|
|
|
[PubMed: 15336973]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.bbrc.2004.08.031]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lynch, P. J., Tong, J., Lehane, M., Mallet, A., Giblin, L., Heffron, J. J. A., Vaughan, P., Zafra, G., MacLennan, D. H., McCarthy, T. V.
|
|
<strong>A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca(2+) release channel function and severe central core disease.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 4164-4169, 1999.
|
|
|
|
|
|
[PubMed: 10097181]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.96.7.4164]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
MacKenzie, A. E., Korneluk, R. G., Zorzato, F., Fujii, J., Phillips, M., Iles, D., Wieringa, B., Leblond, S., Bailly, J., Willard, H. F., Duff, C., Worton, R. G., MacLennan, D. H.
|
|
<strong>The human ryanodine receptor gene: its mapping to 19q13.1, placement in a chromosome 19 linkage group, and exclusion as the gene causing myotonic dystrophy.</strong>
|
|
Am. J. Hum. Genet. 46: 1082-1089, 1990.
|
|
|
|
|
|
[PubMed: 1971150]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
MacLennan, D. H., Zorzato, F., Fujii, J., Otsu, K., Phillips, M., Lai, F. A., Meissner, G., Green, N. M., Willard, H. F., Britt, B. A., Worton, R. G., Korneluk, R. G.
|
|
<strong>Cloning and localization of the human calcium release channel (ryanodine receptor) gene to the proximal long arm (cen-q13.2) of human chromosome 19. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 45 (suppl.): A205 only, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Manning, B. M., Quane, K. A., Lynch, P. J., Urwyler, A., Tegazzin, V., Krivosic-Horber, R., Censier, K., Comi, G., Adnet, P., Wolz, W., Lunardi, J., Muller, C. R., McCarthy, T. V.
|
|
<strong>Novel mutations at a CpG dinucleotide in the ryanodine receptor in malignant hyperthermia.</strong>
|
|
Hum. Mutat. 11: 45-50, 1998.
|
|
|
|
|
|
[PubMed: 9450902]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1998)11:1<45::AID-HUMU7>3.0.CO;2-K]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Manning, B. M., Quane, K. A., Ording, H., Urwyler, A., Tegazzin, V., Lehane, M., O'Halloran, J., Hartung, E., Giblin, L. M., Lynch, P. J., Vaughan, P., Censier, K., Bendixen, D., Comi, G., Heytens, L., Monsieurs, K., Fagerlund, T., Wolz, W., Heffron, J. J. A., Muller, C. R., McCarthy, T. V.
|
|
<strong>Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation.</strong>
|
|
Am. J. Hum. Genet. 62: 599-609, 1998.
|
|
|
|
|
|
[PubMed: 9497245]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/301748]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mattei, M. G., Giannini, G., Moscatelli, F., Sorrentino, V.
|
|
<strong>Chromosomal localization of murine ryanodine receptor genes RYR1, RYR2, and RYR3 by in situ hybridization.</strong>
|
|
Genomics 22: 202-204, 1994.
|
|
|
|
|
|
[PubMed: 7959768]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1994.1362]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McCarthy, T. V., Quane, K. A., Lynch, P. J.
|
|
<strong>Ryanodine receptor mutations in malignant hyperthermia and central core disease.</strong>
|
|
Hum. Mutat. 15: 410-417, 2000.
|
|
|
|
|
|
[PubMed: 10790202]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(200005)15:5<410::AID-HUMU2>3.0.CO;2-D]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McKie, A. B., Alsaedi, A., Vogt, J., Stuurman, K. E., Weiss, M. M., Shakeel, H., Tee, L., Morgan, N. V., Nikkels, P. G. J., van Haaften, G., Park, S.-M., van der Smagt, J. J., Bugiani, M., Maher, E. R.
|
|
<strong>Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome.</strong>
|
|
Acta Neuropath. Commun. 2: 148, 2014. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 25476234]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1186/s40478-014-0148-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Monnier, N., Ferreiro, A., Marty, I., Labarre-Vila, A., Mezin, P., Lunardi, J.
|
|
<strong>A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia.</strong>
|
|
Hum. Molec. Genet. 12: 1171-1178, 2003.
|
|
|
|
|
|
[PubMed: 12719381]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg121]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Monnier, N., Kozak-Ribbens, G., Krivosic-Horber, R., Nivoche, Y., Qi, D., Kraev, N., Loke, J., Sharma, P., Tegazzin, V., Figarella-Branger, D., Romero, N., Mezin, P., Bendahan, D., Payen, J.-F., Depret, T., Maclennan, D. H., Lunardi, J.
|
|
<strong>Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility.</strong>
|
|
Hum. Mutat. 26: 413-425, 2005.
|
|
|
|
|
|
[PubMed: 16163667]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20231]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Monnier, N., Marty, I., Faure, J., Castiglioni, C., Desnuelle, C., Sacconi, S., Estournet, B., Ferreiro, A., Romero, N., Laquerriere, A., Lazaro, L., Martin, J.-J., Morava, E., Rossi, A., Van der Kooi, A., de Visser, M., Verschuuren, C., Lunardi, J.
|
|
<strong>Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.</strong>
|
|
Hum. Mutat. 29: 670-678, 2008.
|
|
|
|
|
|
[PubMed: 18253926]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20696]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Monnier, N., Romero, N. B., Lerale, J., Landrieu, P., Nivoche, Y., Fardeau, M., Lunardi, J.
|
|
<strong>Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor.</strong>
|
|
Hum. Molec. Genet. 10: 2581-2592, 2001.
|
|
|
|
|
|
[PubMed: 11709545]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.22.2581]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Monnier, N., Romero, N. B., Lerale, J., Nivoche, Y., Qi, D., MacLennan, D. H., Fardeau, M., Lunardi, J.
|
|
<strong>An autosomal dominant congenital myopathy with cores and rods is associated with a neomutation in the RYR1 gene encoding the skeletal muscle ryanodine receptor.</strong>
|
|
Hum. Molec. Genet. 9: 2599-2608, 2000.
|
|
|
|
|
|
[PubMed: 11063719]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/9.18.2599]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Monsieurs, K. G., Van Broeckhoven, C., Martin, J.-J., Van Hoof, V. O., Heytens, L.
|
|
<strong>Gly341arg mutation indicating malignant hyperthermia susceptibility: specific cause of chronically elevated serum creatine kinase activity.</strong>
|
|
J. Neurol. Sci. 154: 62-65, 1998.
|
|
|
|
|
|
[PubMed: 9543323]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-510x(97)00215-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
O'Brien, R. O., Taske, N. L., Hansbro, P. M., Matthaei, K. I., Hogan, S. P., Denborough, M. A., Foster, P. S.
|
|
<strong>Exclusion of defects in the skeletal muscle specific regions of the DHPR alpha-1 subunit as frequent causes of malignant hyperthermia.</strong>
|
|
J. Med. Genet. 32: 913-914, 1995.
|
|
|
|
|
|
[PubMed: 8592342]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.32.11.913]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Otsu, K., Khanna, V. K., Archibald, A. L., MacLennan, D. H.
|
|
<strong>Cosegregation of porcine malignant hyperthermia and a probable causal mutation in the skeletal muscle ryanodine receptor gene in backcross families.</strong>
|
|
Genomics 11: 744-750, 1991.
|
|
|
|
|
|
[PubMed: 1774073]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(91)90083-q]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Otsu, K., Nishida, K., Kimura, Y., Kuzuya, T., Hori, M., Kamada, T., Tada, M.
|
|
<strong>The point mutation arg615-to-cys in the Ca(2+) release channel of skeletal sarcoplasmic reticulum is responsible for hypersensitivity to caffeine and halothane in malignant hyperthermia.</strong>
|
|
J. Biol. Chem. 269: 9413-9415, 1994.
|
|
|
|
|
|
[PubMed: 7511586]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Otsu, K., Phillips, M. S., Khanna, V. K., de Leon, S., MacLennan, D. H.
|
|
<strong>Refinement of diagnostic assays for a probable causal mutation for porcine and human malignant hyperthermia.</strong>
|
|
Genomics 13: 835-837, 1992.
|
|
|
|
|
|
[PubMed: 1639409]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(92)90163-m]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Phillips, M. S., Fujii, J., Khanna, V. K., DeLeon, S., Yokobata, K., De Jong, P. J., MacLennan, D. H.
|
|
<strong>The structural organization of the human skeletal muscle ryanodine receptor (RYR1) gene.</strong>
|
|
Genomics 34: 24-41, 1996.
|
|
|
|
|
|
[PubMed: 8661021]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1996.0238]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Quane, K. A., Healy, J. M. S., Keating, K. E., Manning, B. M., Couch, F. J., Palmucci, L. M., Doriguzzi, C., Fagerlund, T. H., Berg, K., Ording, H., Bendixen, D., Mortier, W., Linz, U., Muller, C. R., McCarthy, T. V.
|
|
<strong>Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia.</strong>
|
|
Nature Genet. 5: 51-55, 1993.
|
|
|
|
|
|
[PubMed: 8220423]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0993-51]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Quane, K. A., Keating, K. E., Healy, J. M. S., Manning, B. M., Krivosic-Horber, R., Krivosic, I., Monnier, N., Lunardi, J., McCarthy, T. V.
|
|
<strong>Mutation screening of the RYR1 gene in malignant hyperthermia: detection of a novel tyr to ser mutation in a pedigree with associated central cores.</strong>
|
|
Genomics 23: 236-239, 1994.
|
|
|
|
|
|
[PubMed: 7829078]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1994.1483]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Quane, K. A., Keating, K. E., Manning, B. M., Healy, J. M. S., Monsieurs, K., Heffron, J. J. A., Lehane, M., Heytens, L., Krivosic-Horber, R., Adnet, P., Ellis, F. R., Monnier, N., Lunardi, J., McCarthy, T. V.
|
|
<strong>Detection of a novel common mutation in the ryanodine receptor gene in malignant hyperthermia: implications for diagnosis and heterogeneity studies.</strong>
|
|
Hum. Molec. Genet. 3: 471-476, 1994.
|
|
|
|
|
|
[PubMed: 8012359]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/3.3.471]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Quinlivan, R. M., Muller, C. R., Davis, M., Laing, N. G., Evans, G. A., Dwyer, J., Dove, J., Roberts, A. P., Sewry, C. A.
|
|
<strong>Central core disease: clinical, pathological, and genetic features.</strong>
|
|
Arch. Dis. Child. 88: 1051-1055, 2003.
|
|
|
|
|
|
[PubMed: 14670767]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/adc.88.12.1051]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Richter, M., Schleithoff, L., Deufel, T., Lehmann-Horn, F., Herrmann-Frank, A.
|
|
<strong>Functional characterization of a distinct ryanodine receptor mutation in human malignant hyperthermia-susceptible muscle.</strong>
|
|
J. Biol. Chem. 272: 5256-5260, 1997.
|
|
|
|
|
|
[PubMed: 9030597]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.272.8.5256]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Robinson, R., Carpenter, D., Shaw, M.-A., Halsall, J., Hopkins, P.
|
|
<strong>Mutations in RYR1 in malignant hyperthermia and central core disease.</strong>
|
|
Hum. Mutat. 27: 977-989, 2006.
|
|
|
|
|
|
[PubMed: 16917943]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20356]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Robinson, R. L., Brooks, C., Brown, S. L., Ellis, F. R., Halsall, P. J., Quinnell, R. J., Shaw, M.-A., Hopkins, P. M.
|
|
<strong>RYR1 mutations causing central core disease are associated with more severe malignant hyperthermia in vitro contracture test phenotypes.</strong>
|
|
Hum. Mutat. 20: 88-97, 2002.
|
|
|
|
|
|
[PubMed: 12124989]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.10098]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sambuughin, N., McWilliams, S., de Bantel, A., Sivakumar, K., Nelson, T. E.
|
|
<strong>Single-amino-acid deletion in the RYR1 gene, associated with malignant hyperthermia susceptibility and unusual contraction phenotype.</strong>
|
|
Am. J. Hum. Genet. 69: 204-208, 2001.
|
|
|
|
|
|
[PubMed: 11389482]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/321270]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sato, I., Wu, S., Ibarra, M. C. A., Hayashi, Y. K., Fujita, H., Tojo, M., Oh, S. J., Nonaka, I., Noguchi, S., Nishino, I.
|
|
<strong>Congenital neuromuscular disease with uniform type 1 fiber and RYR1 mutation.</strong>
|
|
Neurology 70: 114-122, 2008.
|
|
|
|
|
|
[PubMed: 17538032]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000269792.63927.86]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scacheri, P. C., Hoffman, E. P., Fratkin, J. D., Semino-Mora, C., Senchak, A., Davis, M. R., Laing, N. G., Vedanarayanan, V., Subramony, S. H.
|
|
<strong>A novel ryanodine receptor gene mutation causing both cores and rods in congenital myopathy.</strong>
|
|
Neurology 55: 1689-1696, 2000.
|
|
|
|
|
|
[PubMed: 11113224]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.55.11.1689]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shuaib, A., Paasuke, R. T., Brownell, K. W.
|
|
<strong>Central core disease: clinical features in 13 patients.</strong>
|
|
Medicine 66: 389-396, 1987.
|
|
|
|
|
|
[PubMed: 3626847]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stewart, S. L., Rosenberg, H., Fletcher, J. E.
|
|
<strong>Failure to identify the ryanodine receptor G1021A mutation in a large North American population with malignant hyperthermia.</strong>
|
|
Clin. Genet. 54: 358-361, 1998.
|
|
|
|
|
|
[PubMed: 9831351]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.1998.5440417.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Swash, M., Schwartz, M. S.
|
|
<strong>Familial multicore disease with focal loss of cross-striations and ophthalmoplegia.</strong>
|
|
J. Neurol. Sci. 52: 1-10, 1981.
|
|
|
|
|
|
[PubMed: 7299413]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0022-510x(81)90129-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Takeshima, H., Iino, M., Takekura, H., Nishi, M., Kuno, J., Minowa, O., Takano, H., Noda, T.
|
|
<strong>Excitation-contraction uncoupling and muscular degeneration in mice lacking functional skeletal muscle ryanodine-receptor gene.</strong>
|
|
Nature 369: 556-559, 1994.
|
|
|
|
|
|
[PubMed: 7515481]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/369556a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Takeshima, H., Yamazawa, T., Ikemoto, T., Takekura, H., Nishi, M., Noda, T., Iino, M.
|
|
<strong>Ca(2+)-induced Ca(2+) release in myocytes from dyspedic mice lacking the type-1 ryanodine receptor.</strong>
|
|
EMBO J. 14: 2999-3006, 1995.
|
|
|
|
|
|
[PubMed: 7621815]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1995.tb07302.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tegazzin, V., Accorsi, A., Gritti, G., Arcelli, L., Di Giovanni, A.
|
|
<strong>MH fulminant reaction after eight anaesthetics: a case report.</strong>
|
|
Minerva Anestesiol. 60: 217-219, 1994.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tilgen, N., Zorzato, F., Halliger-Keller, B., Muntoni, F., Sewry, C., Palumucci, L. M., Schneider, C., Hauser, E., Lehmann-Horn, F., Muller, C. R., Treves, S.
|
|
<strong>Identification of four novel mutations in the C-terminal membrane spanning domain of the ryanodine receptor 1: association with central core disease and alteration of calcium homeostasis.</strong>
|
|
Hum. Molec. Genet. 10: 2879-2887, 2001.
|
|
|
|
|
|
[PubMed: 11741831]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.25.2879]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tobin, J. R., Jason, D. R., Challa, V. R., Nelson, T. E., Sambuughin, N.
|
|
<strong>Malignant hyperthermia and apparent heat stroke. (Letter)</strong>
|
|
JAMA 286: 168-169, 2001.
|
|
|
|
|
|
[PubMed: 11448278]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/jama.286.2.168]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tojo, M., Ozawa, M., Nonaka, I.
|
|
<strong>Central core disease and congenital neuromuscular disease with uniform type 1 fibers in one family.</strong>
|
|
Brain Dev. 22: 262-264, 2000.
|
|
|
|
|
|
[PubMed: 10838116]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0387-7604(00)00108-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Trask, B., Fertitta, A., Christensen, M., Youngblom, J., Bergmann, A., Copeland, A., de Jong, P., Mohrenweiser, H., Olsen, A., Carrano, A., Tynan, K.
|
|
<strong>Fluorescence in situ hybridization mapping of human chromosome 19: cytogenetic band location of 540 cosmids and 70 genes or DNA markers.</strong>
|
|
Genomics 15: 133-145, 1993.
|
|
|
|
|
|
[PubMed: 8432525]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1993.1021]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tung, C.-C., Lobo, P. A., Kimlicka, L., Van Petegem, F.
|
|
<strong>The amino-terminal disease hotspot of ryanodine receptors forms a cytoplasmic vestibule.</strong>
|
|
Nature 468: 585-588, 2010.
|
|
|
|
|
|
[PubMed: 21048710]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature09471]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, S.-Q., Song, L.-S., Lakatta, E. G., Cheng, H.
|
|
<strong>Ca(2+) signalling between single L-type Ca(2+) channels and ryanodine receptors in heart cells.</strong>
|
|
Nature 410: 592-596, 2001.
|
|
|
|
|
|
[PubMed: 11279498]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/35069083]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wehner, M., Rueffert, H., Koenig, F., Neuhaus, J., Olthoff, D.
|
|
<strong>Increased sensitivity to 4-chloro-m-cresol and caffeine in primary myotubes from malignant hyperthermia susceptible individuals carrying the ryanodine receptor 1 thr2206met (C6617T) mutation.</strong>
|
|
Clin. Genet. 62: 135-146, 2002.
|
|
|
|
|
|
[PubMed: 12220451]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2002.620206.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wilmshurst, J. M., Lillis, S., Zhou, H., Pillay, K., Henderson, H., Kress, W., Muller, C. R., Ndondo, A., Cloke, V., Cullup, T., Bertini, E., Boennemann, C., and 10 others.
|
|
<strong>RYR1 mutations are a common cause of congenital myopathies with central nuclei.</strong>
|
|
Ann. Neurol. 68: 717-726, 2010.
|
|
|
|
|
|
[PubMed: 20839240]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.22119]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wu, S., Ibarra M, C. A., Malicdan, M. C. V., Murayama, K., Ichihara, Y., Kikuchi, H., Nonaka, I., Noguchi, S., Hayashi, Y. K., Nishino, I.
|
|
<strong>Central core disease is due to RYR1 mutations in more than 90% of patients.</strong>
|
|
Brain 129: 1470-1480, 2006.
|
|
|
|
|
|
[PubMed: 16621918]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/brain/awl077]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yan, Z., Bai, X., Yan, C., Wu, J., Li, Z., Xie, T., Peng, W., Yin, C., Li, X., Scheres, S. H. W., Shi, Y., Yan, N.
|
|
<strong>Structure of the rabbit ryanodine receptor RyR1 at near-atomic resolution.</strong>
|
|
Nature 517: 50-55, 2015.
|
|
|
|
|
|
[PubMed: 25517095]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature14063]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zalk, R., Clarke, O. B., des Georges, A., Grassucci, R. A., Reiken, S., Mancia, F., Hendrickson, W. A., Frank, J., Marks, A. R.
|
|
<strong>Structure of a mammalian ryanodine receptor.</strong>
|
|
Nature 517: 44-49, 2015.
|
|
|
|
|
|
[PubMed: 25470061]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature13950]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, Y., Chen, H. S., Khanna, V. K., De Leon, S., Phillips, M. S., Schappert, K., Britt, B. A., Brownell, A. K. W., MacLennan, D. H.
|
|
<strong>A mutation in the human ryanodine receptor gene associated with central core disease.</strong>
|
|
Nature Genet. 5: 46-50, 1993.
|
|
|
|
|
|
[PubMed: 8220422]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0993-46]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhou, H., Brockington, M., Jungbluth, H., Monk, D., Stanier, P., Sewry, C. A., Moore, G. E., Muntoni, F.
|
|
<strong>Epigenetic allele silencing unveils recessive RYR1 mutations in core myopathies.</strong>
|
|
Am. J. Hum. Genet. 79: 859-868, 2006.
|
|
|
|
|
|
[PubMed: 17033962]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/508500]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zorzato, F., Fujii, J., Otsu, K., Phillips, M., Green, N. M., Lai, F. A., Meissner, G., MacLennan, D. H.
|
|
<strong>Molecular cloning of cDNA encoding human and rabbit forms of the Ca(2+) release channel (ryanodine receptor) of skeletal muscle sarcoplasmic reticulum.</strong>
|
|
J. Biol. Chem. 265: 2244-2256, 1990.
|
|
|
|
|
|
[PubMed: 2298749]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zorzato, F., Yamaguchi, N., Xu, L., Meissner, G., Muller, C. R., Pouliquin, P., Muntoni, F., Sewry, C., Girard, T., Treves, S.
|
|
<strong>Clinical and functional effects of a deletion in a COOH-terminal lumenal loop of the skeletal muscle ryanodine receptor.</strong>
|
|
Hum. Molec. Genet. 12: 379-388, 2003.
|
|
|
|
|
|
[PubMed: 12566385]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg032]
|
|
|
|
|
|
</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 : 02/24/2023<br>Bao Lige - updated : 01/06/2022<br>Hilary J. Vernon - updated : 10/11/2021<br>Hilary J. Vernon - updated : 08/27/2021<br>Hilary J. Vernon - updated : 11/30/2020<br>Hilary J. Vernon - updated : 10/29/2020<br>Cassandra L. Kniffin - updated : 5/20/2015<br>Ada Hamosh - updated : 3/9/2015<br>Cassandra L. Kniffin - updated : 6/5/2013<br>Cassandra L. Kniffin - updated : 2/16/2011<br>Ada Hamosh - updated : 2/2/2011<br>Cassandra L. Kniffin - updated : 5/28/2009<br>Cassandra L. Kniffin - updated : 1/13/2009<br>Cassandra L. Kniffin - updated : 8/26/2008<br>Victor A. McKusick - updated : 10/9/2006<br>Cassandra L. Kniffin - updated : 10/4/2006<br>Cassandra L. Kniffin - updated : 6/2/2006<br>Cassandra L. Kniffin - updated : 4/6/2006<br>Victor A. McKusick - updated : 11/22/2005<br>George E. Tiller - updated : 2/25/2005<br>Patricia A. Hartz - updated : 2/18/2005<br>George E. Tiller - updated : 1/4/2005<br>Cassandra L. Kniffin - updated : 12/17/2004<br>Cassandra L. Kniffin - reorganized : 6/3/2004<br>Victor A. McKusick - updated : 11/26/2002<br>Victor A. McKusick - updated : 11/5/2002<br>Cassandra L. Kniffin - updated : 10/14/2002<br>Victor A. McKusick - updated : 9/17/2002<br>Victor A. McKusick - updated : 8/20/2002<br>George E. Tiller - updated : 8/13/2002<br>George E. Tiller - updated : 5/14/2002<br>Victor A. McKusick - updated : 8/16/2001<br>Victor A. McKusick - updated : 4/17/2001<br>Ada Hamosh - updated : 4/4/2001<br>George E. Tiller - updated : 1/24/2001<br>George E. Tiller - updated : 10/17/2000<br>Stylianos E. Antonarakis - updated : 9/5/2000<br>Ada Hamosh - updated : 7/20/2000<br>Victor A. McKusick - updated : 5/19/2000<br>Victor A. McKusick - updated : 10/25/1999<br>Victor A. McKusick - updated : 4/13/1999<br>Victor A. McKusick - updated : 1/26/1999<br>Ada Hamosh - updated : 6/12/1998<br>Victor A. McKusick - updated : 5/8/1998<br>Victor A. McKusick - updated : 3/9/1998<br>Victor A. McKusick - updated : 2/25/1998<br>Victor A. McKusick - updated : 2/2/1998<br>Victor A. McKusick - updated : 6/12/1997<br>Victor A. McKusick - updated : 3/12/1997<br>Iosif W. Lurie - updated : 7/26/1996
|
|
</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 : 11/9/1989
|
|
</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">
|
|
alopez : 07/16/2024<br>alopez : 02/27/2023<br>ckniffin : 02/24/2023<br>alopez : 02/21/2023<br>carol : 02/20/2023<br>carol : 02/20/2023<br>carol : 05/18/2022<br>carol : 05/16/2022<br>alopez : 02/23/2022<br>mgross : 01/06/2022<br>carol : 10/11/2021<br>carol : 09/27/2021<br>carol : 08/30/2021<br>carol : 08/27/2021<br>carol : 12/01/2020<br>carol : 11/30/2020<br>carol : 10/29/2020<br>carol : 08/30/2016<br>alopez : 05/22/2015<br>mcolton : 5/21/2015<br>ckniffin : 5/20/2015<br>alopez : 3/9/2015<br>carol : 9/17/2013<br>carol : 7/3/2013<br>tpirozzi : 7/3/2013<br>ckniffin : 6/5/2013<br>terry : 9/7/2012<br>terry : 3/11/2011<br>wwang : 3/10/2011<br>ckniffin : 2/16/2011<br>alopez : 2/7/2011<br>terry : 2/2/2011<br>wwang : 6/10/2009<br>ckniffin : 5/28/2009<br>terry : 2/3/2009<br>wwang : 1/22/2009<br>ckniffin : 1/13/2009<br>wwang : 9/19/2008<br>ckniffin : 8/26/2008<br>wwang : 5/30/2008<br>ckniffin : 4/18/2008<br>alopez : 10/10/2006<br>carol : 10/9/2006<br>carol : 10/9/2006<br>ckniffin : 10/4/2006<br>terry : 7/26/2006<br>wwang : 6/12/2006<br>ckniffin : 6/2/2006<br>carol : 4/18/2006<br>wwang : 4/12/2006<br>ckniffin : 4/6/2006<br>carol : 1/3/2006<br>wwang : 12/8/2005<br>terry : 11/22/2005<br>carol : 8/1/2005<br>carol : 3/28/2005<br>tkritzer : 3/9/2005<br>terry : 2/25/2005<br>mgross : 2/18/2005<br>mgross : 2/18/2005<br>alopez : 1/4/2005<br>tkritzer : 12/29/2004<br>ckniffin : 12/17/2004<br>carol : 6/3/2004<br>ckniffin : 6/1/2004<br>tkritzer : 3/3/2003<br>cwells : 11/26/2002<br>terry : 11/20/2002<br>carol : 11/12/2002<br>tkritzer : 11/11/2002<br>terry : 11/5/2002<br>carol : 10/21/2002<br>ckniffin : 10/14/2002<br>carol : 9/24/2002<br>tkritzer : 9/17/2002<br>tkritzer : 9/17/2002<br>tkritzer : 8/26/2002<br>tkritzer : 8/23/2002<br>terry : 8/20/2002<br>cwells : 8/13/2002<br>cwells : 5/17/2002<br>cwells : 5/14/2002<br>alopez : 10/30/2001<br>cwells : 9/7/2001<br>cwells : 8/27/2001<br>terry : 8/16/2001<br>terry : 8/16/2001<br>mcapotos : 5/9/2001<br>mcapotos : 4/25/2001<br>terry : 4/17/2001<br>alopez : 4/5/2001<br>terry : 4/4/2001<br>mcapotos : 2/1/2001<br>mcapotos : 1/24/2001<br>alopez : 10/17/2000<br>mgross : 9/5/2000<br>carol : 8/10/2000<br>mcapotos : 8/1/2000<br>mcapotos : 7/26/2000<br>mcapotos : 7/26/2000<br>terry : 7/20/2000<br>mcapotos : 6/6/2000<br>mcapotos : 6/5/2000<br>mcapotos : 5/25/2000<br>terry : 5/19/2000<br>mgross : 11/4/1999<br>mgross : 11/3/1999<br>terry : 10/25/1999<br>carol : 4/13/1999<br>terry : 4/13/1999<br>carol : 1/26/1999<br>terry : 6/17/1998<br>alopez : 6/12/1998<br>alopez : 5/15/1998<br>terry : 5/8/1998<br>alopez : 3/9/1998<br>terry : 2/25/1998<br>terry : 2/25/1998<br>mark : 2/3/1998<br>terry : 2/2/1998<br>terry : 7/7/1997<br>mark : 6/22/1997<br>mark : 6/18/1997<br>mark : 6/16/1997<br>terry : 6/12/1997<br>terry : 3/12/1997<br>terry : 3/6/1997<br>carol : 7/26/1996<br>carol : 7/15/1996<br>terry : 6/5/1996<br>terry : 6/3/1996<br>mark : 1/31/1996<br>terry : 1/24/1996<br>terry : 8/3/1995<br>mark : 6/28/1995<br>mimadm : 3/25/1995<br>carol : 9/30/1994<br>warfield : 4/21/1994<br>carol : 9/15/1993
|
|
</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>
|
|
|
|
|