4496 lines
360 KiB
Text
4496 lines
360 KiB
Text
|
|
|
|
|
|
|
|
|
|
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
|
|
|
|
<head>
|
|
|
|
|
|
|
|
<!--
|
|
################################# CRAWLER WARNING #################################
|
|
|
|
- The terms of service and the robots.txt file disallows crawling of this site,
|
|
please see https://omim.org/help/agreement for more information.
|
|
|
|
- A number of data files are available for download at https://omim.org/downloads.
|
|
|
|
- We have an API which you can learn about at https://omim.org/help/api and register
|
|
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
|
|
|
|
- You should feel free to contact us at https://omim.org/contact to figure out the best
|
|
approach to getting the data you need for your work.
|
|
|
|
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
|
|
|
|
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
|
|
DISTRIBUTED CRAWLS OF THIS SITE.
|
|
|
|
################################# CRAWLER WARNING #################################
|
|
-->
|
|
|
|
|
|
|
|
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
|
|
<meta http-equiv="cache-control" content="no-cache" />
|
|
<meta http-equiv="pragma" content="no-cache" />
|
|
<meta name="robots" content="index, follow" />
|
|
|
|
|
|
<meta name="viewport" content="width=device-width, initial-scale=1" />
|
|
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
|
|
|
|
|
|
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
|
|
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
|
|
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
|
|
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
|
|
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
|
|
contain copious links to other genetics resources." />
|
|
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
|
|
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
|
|
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
|
|
<meta name="theme-color" content="#333333" />
|
|
<link rel="icon" href="/static/omim/favicon.png" />
|
|
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
|
|
<link rel="manifest" href="/static/omim/manifest.json" />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script id='mimBrowserCapability'>
|
|
function _0x5069(){const _0x4b1387=['91sZIeLc','mimBrowserCapability','15627zshTnf','710004yxXedd','34LxqNYj','match','disconnect','1755955rnzTod','observe','1206216ZRfBWB','575728fqgsYy','webdriver','documentElement','close','open','3086704utbakv','7984143PpiTpt'];_0x5069=function(){return _0x4b1387;};return _0x5069();}function _0xe429(_0x472ead,_0x43eb70){const _0x506916=_0x5069();return _0xe429=function(_0xe42949,_0x1aaefc){_0xe42949=_0xe42949-0x1a9;let _0xe6add8=_0x506916[_0xe42949];return _0xe6add8;},_0xe429(_0x472ead,_0x43eb70);}(function(_0x337daa,_0x401915){const _0x293f03=_0xe429,_0x5811dd=_0x337daa();while(!![]){try{const _0x3dc3a3=parseInt(_0x293f03(0x1b4))/0x1*(-parseInt(_0x293f03(0x1b6))/0x2)+parseInt(_0x293f03(0x1b5))/0x3+parseInt(_0x293f03(0x1b0))/0x4+-parseInt(_0x293f03(0x1b9))/0x5+parseInt(_0x293f03(0x1aa))/0x6+-parseInt(_0x293f03(0x1b2))/0x7*(parseInt(_0x293f03(0x1ab))/0x8)+parseInt(_0x293f03(0x1b1))/0x9;if(_0x3dc3a3===_0x401915)break;else _0x5811dd['push'](_0x5811dd['shift']());}catch(_0x4dd27b){_0x5811dd['push'](_0x5811dd['shift']());}}}(_0x5069,0x84d63),(function(){const _0x9e4c5f=_0xe429,_0x363a26=new MutationObserver(function(){const _0x458b09=_0xe429;if(document!==null){let _0x2f0621=![];navigator[_0x458b09(0x1ac)]!==![]&&(_0x2f0621=!![]);for(const _0x427dda in window){_0x427dda[_0x458b09(0x1b7)](/cdc_[a-z0-9]/ig)&&(_0x2f0621=!![]);}_0x2f0621===!![]?document[_0x458b09(0x1af)]()[_0x458b09(0x1ae)]():(_0x363a26[_0x458b09(0x1b8)](),document['getElementById'](_0x458b09(0x1b3))['remove']());}});_0x363a26[_0x9e4c5f(0x1a9)](document[_0x9e4c5f(0x1ad)],{'childList':!![]});}()));
|
|
</script>
|
|
|
|
|
|
|
|
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
|
|
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
|
|
|
|
<link rel="preconnect" href="https://www.googletagmanager.com" />
|
|
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
|
|
<script>
|
|
window.dataLayer = window.dataLayer || [];
|
|
function gtag(){window.dataLayer.push(arguments);}
|
|
gtag("js", new Date());
|
|
gtag("config", "G-HMPSQC23JJ");
|
|
</script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
|
|
|
|
|
|
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
|
|
|
|
|
|
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimBootstrapDeviceSize">
|
|
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
|
|
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
|
|
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
|
|
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
|
|
</div>
|
|
|
|
|
|
|
|
<title>
|
|
|
|
Entry
|
|
|
|
- *120250 - COLLAGEN, TYPE VI, ALPHA-3; COL6A3
|
|
|
|
|
|
- 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=120250"><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">*120250</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="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/120250">Table View</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000163359;t=ENST00000295550" 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=1293" 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=120250" 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=ENSG00000163359;t=ENST00000295550" 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_004369,NM_057164,NM_057165,NM_057166,NM_057167" 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_004369" 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=120250" 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=00371&isoform_id=00371_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/COL6A3" 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/260297,291920,1335034,3127926,21620053,34365490,52545928,55743098,55743106,62088852,62822357,62988748,119591509,119591510,119591511,119591512,119591513,119591514,119591515,119591516,193787261,194381994,194389238,219521324,219841772,223462379,240255535,240255540,240255542,302313173,308219876,311033499" 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/P12111" 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=1293" 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=ENSG00000163359;t=ENST00000295550" 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=COL6A3" 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=COL6A3" 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+1293" 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/COL6A3" 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:1293" 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/1293" 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=chr2&hgg_gene=ENST00000295550.9&hgg_start=237324018&hgg_end=237414164&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/genes/HGNC:2213" 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/col6a3" 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=120250[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=120250[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/COL6A3/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/ENSG00000163359" 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=COL6A3" 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=COL6A3" 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=COL6A3" 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/COL6A3" 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=COL6A3&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/PA26729" 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:2213" 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://www.mousephenotype.org/data/genes/MGI:88461" 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/COL6A3#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:88461" 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/1293/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/results?search_type=advanced&omia_id=002260,002274" class="mim-tip-hint" title="OMIA" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OMIA', 'domain': 'omia.angis.org.au'})">OMIA</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=1293" 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=WBGene00020128;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-070501-8" 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:120250" 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:1293" 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=COL6A3&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> 1220573009<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>
|
|
120250
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
COLLAGEN, TYPE VI, ALPHA-3; COL6A3
|
|
|
|
</span>
|
|
</h3>
|
|
</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=COL6A3" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">COL6A3</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/2/1149?start=-3&limit=10&highlight=1149">2q37.3</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:237324018-237414164&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'})">2:237,324,018-237,414,164</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=620726,616411,620728" 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="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/2/1149?start=-3&limit=10&highlight=1149">
|
|
2q37.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Bethlem myopathy 1C
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/620726"> 620726 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <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">
|
|
Dystonia 27
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/616411"> 616411 </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">
|
|
Ullrich congenital muscular dystrophy 1C
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/620728"> 620728 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/120250" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/120250" 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 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
|
|
<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 id="mimTextFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>The COL6A3 gene encodes the alpha-3 chain of type VI collagen. See also COL6A1 (<a href="/entry/120220">120220</a>).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#3" class="mim-tip-reference" title="Chu, M.-L., Zhang, R.-Z., Pan, T.-C., Stokes, D., Conway, D., Kuo, H.-J., Glanville, R., Mayer, U., Mann, K., Deutzmann, R., Timpl, R. <strong>Mosaic structure of globular domains in the human type VI collagen alpha-3 chain: similarity to von Willebrand factor, fibronectin, actin, salivary proteins and apotinin type protease inhibitors.</strong> EMBO J. 9: 385-393, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1689238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1689238</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1990.tb08122.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1689238">Chu et al. (1990)</a> isolated and sequenced human cDNA clones corresponding to the COL6A3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1689238" 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="Klewer, S. E., Krob, S. L., Kolker, S. J., Kitten, G. T. <strong>Expression of type VI collagen in the developing mouse heart.</strong> Dev. Dyn. 211: 248-255, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9520112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9520112</a>] [<a href="https://doi.org/10.1002/(SICI)1097-0177(199803)211:3<248::AID-AJA6>3.0.CO;2-H" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9520112">Klewer et al. (1998)</a> studied COL6A3 gene expression in the developing mammalian heart. The pattern of expression was identical to that of COL6A1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9520112" 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 microarray analysis, <a href="#6" class="mim-tip-reference" title="Jun, A. S., Liu, S. H., Koo, E. H., Do, D. V., Stark, W. J., Gottsch, J. D. <strong>Microarray analysis of gene expression in human donor corneas.</strong> Arch. Ophthal. 119: 1629-1634, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709013/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709013</a>] [<a href="https://doi.org/10.1001/archopht.119.11.1629" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11709013">Jun et al. (2001)</a> demonstrated expression of the COL6A3 gene in human donor corneas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709013" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Zech, M., Lam, D. D., Francescatto, L., Schormair, B., Salminen, A. V., Jochim, A., Wieland, T., Lichtner, P., Peters, A., Gieger, C., Lochmuller, H., Strom, T. M., Haslinger, B., Katsanis, N., Winkelmann, J. <strong>Recessive mutations in the alpha-3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia.</strong> Am. J. Hum. Genet. 96: 883-893, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26004199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26004199</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26004199[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.ajhg.2015.04.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26004199">Zech et al. (2015)</a> found expression of the Col6a3 gene in neurons of the mouse brain, including in the cerebellum and striatum, with highest expression in the brainstem and midbrain. Astroglia did not express Col6a3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26004199" 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="#14" class="mim-tip-reference" title="Stokes, D. G., Saitta, B., Timpl, R., Chu, M.-L. <strong>Human alpha-3(VI) collagen gene: characterization of exons coding for the amino-terminal globular domain and alternative splicing in normal and tumor cells.</strong> J. Biol. Chem. 266: 8626-8633, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2022673/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2022673</a>]" pmid="2022673">Stokes et al. (1991)</a> reported information on the exons for part of the COL6A3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2022673" 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>Weil et al. (<a href="#16" class="mim-tip-reference" title="Weil, D., Mattei, M.-G., Passage, E., Van Cong, N., Pribula-Conway, D., Mann, K., Deutzmann, R., Timpl, R., Chu, M.-L. <strong>Assignment of the three genes coding for the different chains of type VI collagen (COL6A1, COL6A2, COL6A3). (Abstract)</strong> Cytogenet. Cell Genet. 46: 713 only, 1987."None>1987</a>, <a href="#17" class="mim-tip-reference" title="Weil, D., Mattei, M.-G., Passage, E., Van Cong, N., Pribula-Conway, D., Mann, K., Deutzmann, R., Timpl, R., Chu, M.-L. <strong>Cloning and chromosomal localization of human genes encoding the three chains of type VI collagen.</strong> Am. J. Hum. Genet. 42: 435-445, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3348212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3348212</a>]" pmid="3348212">1988</a>) localized the COL6A3 gene to chromosome 2q37 by Southern blot analysis of somatic cell hybrids and by in situ hybridization. At least 3 other extracellular matrix genes are also located on 2q: 2 collagen genes, COL3A1 (<a href="/entry/120180">120180</a>) and COL5A2 (<a href="/entry/120190">120190</a>), and the fibronectin gene (<a href="/entry/135600">135600</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3348212" 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 fluorescence in situ hybridization, <a href="#13" class="mim-tip-reference" title="Speer, M. C., Tandan, R., Rao, P. N., Fries, T., Stajich, J. M., Bolhuis, P. A., Jobsis, G. J., Vance, J. M., Viles, K. D., Sheffield, K., James, C., Kahler, S. G., Pettenati, M., Gilbert, J. R., Denton, P. H., Yamaoka, L. H., Pericak-Vance, M. A. <strong>Evidence for locus heterogeneity in the Bethlem myopathy and linkage to 2q37.</strong> Hum. Molec. Genet. 5: 1043-1046, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8817344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8817344</a>] [<a href="https://doi.org/10.1093/hmg/5.7.1043" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8817344">Speer et al. (1996)</a> localized the COL6A3 gene to chromosome 2q37 within a 17-cM region spanned by D2S336 and D2S395. By linkage analysis, they mapped a candidate gene for Bethlem myopathy (<a href="/entry/620726">620726</a>) to the same chromosomal region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8817344" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Bethlem Myopathy 1C and Ullrich Congenital Muscular Dystrophy 1C</em></strong></p><p>
|
|
<a href="#11" class="mim-tip-reference" title="Pan, T.-C., Zhang, R.-Z., Pericak-Vance, M. A., Tandan, R., Fries, T., Stajich, J. M., Viles, K., Vance, J. M., Chu, M.-L., Speer, M. C. <strong>Missense mutation in a von Willebrand factor type A domain of the alpha-3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy.</strong> Hum. Molec. Genet. 7: 807-812, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9536084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9536084</a>] [<a href="https://doi.org/10.1093/hmg/7.5.807" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9536084">Pan et al. (1998)</a> identified a heterozygous mutation in the COL6A3 gene (<a href="#0001">120250.0001</a>) in affected members of a large American pedigree of French Canadian descent (family 1949) with Bethlem myopathy-1C (BTHLM1C; <a href="/entry/620726">620726</a>), a rare proximal myopathy characterized by early childhood onset and joint contractures. The mutation segregated with the disorder in the family, which was originally reported by <a href="#9" class="mim-tip-reference" title="Mohire, M. D., Tandan, R., Fries, T. J., Little, B. W., Pendlebury, W. W., Bradley, W. G. <strong>Early-onset benign autosomal dominant limb-girdle myopathy with contractures (Bethlem myopathy).</strong> Neurology 38: 573-580, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3352914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3352914</a>] [<a href="https://doi.org/10.1212/wnl.38.4.573" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3352914">Mohire et al. (1988)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9536084+3352914" 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 unrelated patients with Bethlem myopathy, <a href="#1" class="mim-tip-reference" title="Baker, N. L., Morgelin, M., Pace, R. A., Peat, R. A., Adams, N. E., Gardner, R. J. M., Rowland, L. P., Miller, G., De Jonghe, P., Ceulemans, B., Hannibal, M. C., Edwards, M., Thompson, E. M., Jacobson, R., Quinlivan, R. C. M., Aftimos, S., Kornberg, A. J., North, K. N., Bateman, J. F., Lamande, S. R. <strong>Molecular consequences of dominant Bethlem myopathy collagen VI mutations.</strong> Ann. Neurol. 62: 390-405, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17886299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17886299</a>] [<a href="https://doi.org/10.1002/ana.21213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17886299">Baker et al. (2007)</a> identified different heterozygous mutations in the COL6A3 gene (<a href="#0005">120250.0005</a>; <a href="#0006">120250.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17886299" 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>Ullrich congenital muscular dystrophy-1C (UCMD1C; <a href="/entry/620728">620728</a>) is characterized by generalized muscular weakness, contractures of multiple joints, and distal hyperextensibility. <a href="#4" class="mim-tip-reference" title="Demir, E., Sabatelli, P., Allamand, V., Ferreiro, A., Moghadaszadeh, B., Makrelouf, M., Topaloglu, H., Echenne, B., Merlini, E., Guicheney, P. <strong>Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy.</strong> Am. J. Hum. Genet. 70: 1446-1458, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11992252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11992252</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11992252[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/10.1086/340608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11992252">Demir et al. (2002)</a> demonstrated linkage of UCMD to 2q37 in 3 families, each of which demonstrated homozygous mutation in the COL6A3 gene (see, e.g., <a href="#0002">120250.0002</a> and <a href="#0003">120250.0003</a>). One family (family I) had a phenotype of intermediate severity, a second (family II) had an unusually mild phenotype, and a third (family III) had a severe phenotype as previously described in patients with UCMD. This was the first description of mutations in COL6A3 in UCMD; mutations had previously been described in COL6A2 (<a href="/entry/120240">120240</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11992252" 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="Lampe, A. K., Dunn, D. M., von Niederhausern, A. C., Hamil, C., Aoyagi, A., Laval, S. H., Marie, S. K., Chu, M.-L., Swoboda, K., Muntoni, F., Bonnemann, C. G., Flanigan, K. M., Bushby, K. M. D., Weiss, R. B. <strong>Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy.</strong> J. Med. Genet. 42: 108-120, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15689448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15689448</a>] [<a href="https://doi.org/10.1136/jmg.2004.023754" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15689448">Lampe et al. (2005)</a> developed a method for rapid direct sequence analysis of all 107 coding exons of the COL6 genes (COL6A1, COL6A2, COL6A3) using single condition amplification/internal primer (SCAIP) sequencing. They sequenced all 3 COL6 genes from genomic DNA in 79 patients with UCMD or Bethlem myopathy, and found putative mutations in one of the COL6 genes in 62% of patients. Some patients showed changes in more than one of the COL6 genes, and some UCMD patients appeared to have dominant rather than recessive disease. <a href="#8" class="mim-tip-reference" title="Lampe, A. K., Dunn, D. M., von Niederhausern, A. C., Hamil, C., Aoyagi, A., Laval, S. H., Marie, S. K., Chu, M.-L., Swoboda, K., Muntoni, F., Bonnemann, C. G., Flanigan, K. M., Bushby, K. M. D., Weiss, R. B. <strong>Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy.</strong> J. Med. Genet. 42: 108-120, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15689448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15689448</a>] [<a href="https://doi.org/10.1136/jmg.2004.023754" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15689448">Lampe et al. (2005)</a> concluded that these findings may explain some or all of the cases of UCMD that are unlinked to the COL6 genes under a recessive model. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15689448" 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="Nadeau, A., Kinali, M., Main, M., Jimenez-Mallebrera, C., Aloysius, A., Clement, E., North, B., Manzur, A. Y., Robb, S. A., Mercuri, E., Muntoni, F. <strong>Natural history of Ullrich congenital muscular dystrophy.</strong> Neurology 73: 25-31, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19564581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19564581</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181aae851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19564581">Nadeau et al. (2009)</a> identified a recurrent de novo heterozygous splice site mutation in the COL6A3 gene (<a href="#0004">120250.0004</a>) in 2 unrelated individuals with UCMD1C. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19564581" 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 brothers (P9A and P9B) with variable manifestations of autosomal recessive Bethlem myopathy-1C (BTHLM1C; <a href="/entry/620726">620726</a>), <a href="#12" class="mim-tip-reference" title="Panades-de Oliveira, L., Rodriguez-Lopez, C., Cantero Montenegro, D., Marcos Toledano, M. D. M., Fernandez-Marmiesse, A., Esteban Perez, J., Hernandez Lain, A., Dominguez-Gonzalez, C. <strong>Bethlem myopathy: a series of 16 patients and description of seven new associated mutations.</strong> J. Neurol. 266: 934-941, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30706156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30706156</a>] [<a href="https://doi.org/10.1007/s00415-019-09217-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30706156">Panades-de Oliveira et al. (2019)</a> identified a homozygous missense variant in the COL6A3 gene (K2483E; <a href="#0012">120250.0012</a>). Another patient (P8A) with the disorder was compound heterozygous for K2483E and a frameshift mutation (c.8540delA; <a href="#0013">120250.0013</a>). The mutations were found by next-generation sequencing and confirmed by Sanger sequencing. Functional studies of the variants and studies of patient cells were not performed. P9A, a 42-year-old man, had onset of proximal muscle weakness in childhood, whereas his brother (P9B) was almost asymptomatic at 48 years of age, except for hyperCKemia and distal contractures. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30706156" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Villar-Quiles, R. N., Donkervoort, S., de Becdelievre, A., Gartioux, C., Jobic, V., Foley, A. R., McCarty, R. M., Hu, Y., Menassa, R., Michel, L., Gousse, G., Lacour, A., and 20 others. <strong>Clinical and molecular spectrum associated with COL6A3 c.7447A-G p.(Lys2483Glu) variant: elucidating its role in collagen VI-related myopathies.</strong> J. Neuromusc. Dis. 8: 633-645, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33749658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33749658</a>] [<a href="https://doi.org/10.3233/JND-200577" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33749658">Villar-Quiles et al. (2021)</a> reported 16 patients with autosomal recessive BTHLM1C associated with the K2483E substitution in the COL6A3 gene (<a href="#0012">120250.0012</a>). Four unrelated patients were homozygous for the mutation, and 12 patients from 10 families carried it in the compound heterozygous state with another putative loss-of-function COL6A3 mutation (see, e.g., R1597X, <a href="#0014">120250.0014</a>). Segregation studies, performed in 8 families, confirmed that the unaffected parents were heterozygous carriers. Fibroblasts derived from 5 of the compound heterozygous patients showed reduced collagen VI secretion, which was most likely due to the second loss-of-function COL6A3 variant. In contrast, fibroblasts from 3 patients who were homozygous for the K2483E variant showed essentially normal collagen VI secretion in 2 and mildly reduced secretion in 1, suggesting that the missense variant does not significantly impact COL6 assembly and secretion. <a href="#15" class="mim-tip-reference" title="Villar-Quiles, R. N., Donkervoort, S., de Becdelievre, A., Gartioux, C., Jobic, V., Foley, A. R., McCarty, R. M., Hu, Y., Menassa, R., Michel, L., Gousse, G., Lacour, A., and 20 others. <strong>Clinical and molecular spectrum associated with COL6A3 c.7447A-G p.(Lys2483Glu) variant: elucidating its role in collagen VI-related myopathies.</strong> J. Neuromusc. Dis. 8: 633-645, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33749658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33749658</a>] [<a href="https://doi.org/10.3233/JND-200577" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33749658">Villar-Quiles et al. (2021)</a> suggested that this missense variant may act as a modulator of the clinical phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33749658" 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>Dystonia 27</em></strong></p><p>
|
|
In affected members of 3 unrelated German families with autosomal recessive dystonia-27 (DYT27; <a href="/entry/616411">616411</a>), <a href="#18" class="mim-tip-reference" title="Zech, M., Lam, D. D., Francescatto, L., Schormair, B., Salminen, A. V., Jochim, A., Wieland, T., Lichtner, P., Peters, A., Gieger, C., Lochmuller, H., Strom, T. M., Haslinger, B., Katsanis, N., Winkelmann, J. <strong>Recessive mutations in the alpha-3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia.</strong> Am. J. Hum. Genet. 96: 883-893, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26004199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26004199</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26004199[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.ajhg.2015.04.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26004199">Zech et al. (2015)</a> identified compound heterozygous mutations in the COL6A3 gene (<a href="#0007">120250.0007</a>-<a href="#0011">120250.0011</a>) that segregated with the disorder in each family. The mutations in the first family were found by exome sequencing; mutations in the subsequent 2 families were found by sequencing exons 41 and 42 of the COL6A3 gene in 367 German cases with isolated dystonia. All patients carried mutations affecting the C terminus, with at least 1 mutation specifically affecting exon 41. The patients presented before age 25 years with isolated dystonia mainly affecting the craniocervical region and the upper limbs. None of the patients had signs of muscular involvement, and patient fibroblasts showed normal distribution and organization of collagen VI. Functional studies of the variants were not performed, but selective knockdown of the zebrafish ortholog resulted in axonal targeting defects. <a href="#18" class="mim-tip-reference" title="Zech, M., Lam, D. D., Francescatto, L., Schormair, B., Salminen, A. V., Jochim, A., Wieland, T., Lichtner, P., Peters, A., Gieger, C., Lochmuller, H., Strom, T. M., Haslinger, B., Katsanis, N., Winkelmann, J. <strong>Recessive mutations in the alpha-3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia.</strong> Am. J. Hum. Genet. 96: 883-893, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26004199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26004199</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26004199[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.ajhg.2015.04.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26004199">Zech et al. (2015)</a> hypothesized that perturbation of the brain extracellular matrix may underlie this form of dystonia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26004199" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#18" class="mim-tip-reference" title="Zech, M., Lam, D. D., Francescatto, L., Schormair, B., Salminen, A. V., Jochim, A., Wieland, T., Lichtner, P., Peters, A., Gieger, C., Lochmuller, H., Strom, T. M., Haslinger, B., Katsanis, N., Winkelmann, J. <strong>Recessive mutations in the alpha-3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia.</strong> Am. J. Hum. Genet. 96: 883-893, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26004199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26004199</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26004199[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.ajhg.2015.04.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26004199">Zech et al. (2015)</a> found that morpholino knockdown of exon 42 of the zebrafish col6a3 gene, which corresponds to exon 41 of the human COL6A3 gene, caused dose-dependent motor neuron pathfinding, branching, and extension errors without overt collagen defects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26004199" 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>14 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/120250" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=120250[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 BETHLEM MYOPATHY 1C, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
COL6A3, GLY1679GLU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121434553 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434553;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=rs121434553" 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=rs121434553" 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=RCV000018689 OR RCV000790696 OR RCV003764588" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018689, RCV000790696, RCV003764588" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018689...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a large American kindred of French Canadian descent (family 1489) with Bethlem myopathy (BTHLM1C; <a href="/entry/620726">620726</a>), originally reported by <a href="#9" class="mim-tip-reference" title="Mohire, M. D., Tandan, R., Fries, T. J., Little, B. W., Pendlebury, W. W., Bradley, W. G. <strong>Early-onset benign autosomal dominant limb-girdle myopathy with contractures (Bethlem myopathy).</strong> Neurology 38: 573-580, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3352914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3352914</a>] [<a href="https://doi.org/10.1212/wnl.38.4.573" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3352914">Mohire et al. (1988)</a> and linked to chromosome 2 by <a href="#13" class="mim-tip-reference" title="Speer, M. C., Tandan, R., Rao, P. N., Fries, T., Stajich, J. M., Bolhuis, P. A., Jobsis, G. J., Vance, J. M., Viles, K. D., Sheffield, K., James, C., Kahler, S. G., Pettenati, M., Gilbert, J. R., Denton, P. H., Yamaoka, L. H., Pericak-Vance, M. A. <strong>Evidence for locus heterogeneity in the Bethlem myopathy and linkage to 2q37.</strong> Hum. Molec. Genet. 5: 1043-1046, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8817344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8817344</a>] [<a href="https://doi.org/10.1093/hmg/5.7.1043" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8817344">Speer et al. (1996)</a>, <a href="#11" class="mim-tip-reference" title="Pan, T.-C., Zhang, R.-Z., Pericak-Vance, M. A., Tandan, R., Fries, T., Stajich, J. M., Viles, K., Vance, J. M., Chu, M.-L., Speer, M. C. <strong>Missense mutation in a von Willebrand factor type A domain of the alpha-3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy.</strong> Hum. Molec. Genet. 7: 807-812, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9536084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9536084</a>] [<a href="https://doi.org/10.1093/hmg/7.5.807" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9536084">Pan et al. (1998)</a> identified a heterozygous G-to-A transition in the COL6A3 gene, resulting in a gly1679-to-glu (G1679E) substitution in the N-terminal globular domain of the protein, rather than in the triple-helical domain where mutations had been found in the COL6A1 (<a href="/entry/120220">120220</a>) and COL6A2 (<a href="/entry/120240">120240</a>) genes. The mutation occurred in the N2 subdomain, one of the von Willebrand factor type A domains of the COL6A3 gene. The mutation segregated with the disorder in the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9536084+8817344+3352914" 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 ULLRICH CONGENITAL MUSCULAR DYSTROPHY 1C, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
COL6A3, IVS29, A-G, +5
|
|
</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> rs749037028 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs749037028;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/rs749037028?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=rs749037028" 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=rs749037028" 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=RCV000018690 OR RCV003517127 OR RCV003764589" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018690, RCV003517127, RCV003764589" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018690...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 sibs, a brother and 2 sisters, with consanguineous parents originating from Morocco (family I), <a href="#4" class="mim-tip-reference" title="Demir, E., Sabatelli, P., Allamand, V., Ferreiro, A., Moghadaszadeh, B., Makrelouf, M., Topaloglu, H., Echenne, B., Merlini, E., Guicheney, P. <strong>Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy.</strong> Am. J. Hum. Genet. 70: 1446-1458, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11992252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11992252</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11992252[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/10.1086/340608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11992252">Demir et al. (2002)</a> identified homozygosity for a splice donor site mutation in intron 29 (c.6930+5A-G) as the cause of autosomal recessive Ullrich congenital muscular dystrophy (UCMD1C; <a href="/entry/620728">620728</a>). The phenotype was of intermediate severity. The mutation caused skipping of exon 29 and partial reduction of collagen VI in muscle biopsy. Neonatal hypotonia, severe in most cases, was found in all 5 cases in the 3 families reported by <a href="#4" class="mim-tip-reference" title="Demir, E., Sabatelli, P., Allamand, V., Ferreiro, A., Moghadaszadeh, B., Makrelouf, M., Topaloglu, H., Echenne, B., Merlini, E., Guicheney, P. <strong>Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy.</strong> Am. J. Hum. Genet. 70: 1446-1458, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11992252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11992252</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11992252[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/10.1086/340608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11992252">Demir et al. (2002)</a>. In this family the 2 eldest sibs were never able to walk without support (calipers or walking frame). Generalized muscle weakness, associated with predominantly distal amyotrophy, became evident in the first years of life. Axial muscles (mainly neck flexors), pelvic girdle muscles, and intrinsic muscles in hands and feet were the most severely affected ones. Lower limbs tended to be more severely affected than upper limbs; in most cases, hip extensors and abductors were weaker than hip flexors, leading to hip contractures that interfered with standing position. No significant facial weakness was observed. CK levels were normal or moderately raised (up to 4 times the normal values). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11992252" 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 ULLRICH CONGENITAL MUSCULAR DYSTROPHY 1C, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
COL6A3, ARG465TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121434554 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434554;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=rs121434554" 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=rs121434554" 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=RCV002247356 OR RCV003764590" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002247356, RCV003764590" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002247356...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a girl of Italian extraction (family II) with unusually mild Ullrich congenital muscular dystrophy (UCMD1C; <a href="/entry/620728">620728</a>), <a href="#4" class="mim-tip-reference" title="Demir, E., Sabatelli, P., Allamand, V., Ferreiro, A., Moghadaszadeh, B., Makrelouf, M., Topaloglu, H., Echenne, B., Merlini, E., Guicheney, P. <strong>Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy.</strong> Am. J. Hum. Genet. 70: 1446-1458, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11992252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11992252</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11992252[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/10.1086/340608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11992252">Demir et al. (2002)</a> found a homozygous nonsense mutation in exon 5 of the COL6A3 gene: arg465 to ter (R465X). Analysis of the patient's COL6A3 transcript showed the presence of various mRNA species, one of which lacked several exons, including the exon containing the nonsense mutation. The patient in this case was still ambulant at age 18 and showed an unusual combination of hyperlaxity and finger contractures (see Figure 2). When the wrist was extended, the retraction of finger flexor muscles impeded complete finger extension, causing flexion contractures of fingers, which is regarded as a characteristic 'Bethlem' sign. When the wrist was not extended, the finger laxity became evident. The patient was able to overlap, cross, or extend fingers beyond the normal range of motion ('Ullrich sign'). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11992252" 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 ULLRICH CONGENITAL MUSCULAR DYSTROPHY 1C, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
COL6A3, IVS16DS, G-A, +1
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs398124126 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398124126;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=rs398124126" 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=rs398124126" 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=RCV000080961 OR RCV000175056 OR RCV000817699 OR RCV003764764" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000080961, RCV000175056, RCV000817699, RCV003764764" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000080961...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient (UCMD5) with Ullrich congenital muscular dystrophy (UCMD1C; <a href="/entry/620728">620728</a>), <a href="#2" class="mim-tip-reference" title="Baker, N. L., Morgelin, M., Peat, R., Goemans, N., North, K. N., Bateman, J. F., Lamande, S. R. <strong>Dominant collagen VI mutations are a common cause of Ullrich congenital muscular dystrophy.</strong> Hum. Molec. Genet. 14: 279-293, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15563506/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15563506</a>] [<a href="https://doi.org/10.1093/hmg/ddi025" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15563506">Baker et al. (2005)</a> identified heterozygosity for a de novo splice site mutation (IVS16DS+1G-A) in intron 16 of the COL6A3 gene. The mutation was predicted to result in loss of exon 16, which encodes amino acids 13 to 33 of the triple helical region of COL6A3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15563506" 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="Nadeau, A., Kinali, M., Main, M., Jimenez-Mallebrera, C., Aloysius, A., Clement, E., North, B., Manzur, A. Y., Robb, S. A., Mercuri, E., Muntoni, F. <strong>Natural history of Ullrich congenital muscular dystrophy.</strong> Neurology 73: 25-31, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19564581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19564581</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181aae851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19564581">Nadeau et al. (2009)</a> identified a recurrent de novo heterozygous IVS16DS+1G-A mutation in 2 unrelated patients with UCMD1C. The first patient was a 30-year-old individual who had onset at birth with hypotonia, congenital hip dislocation, delayed motor development, and feeding difficulties. Independent walking was not achieved, and the patient became wheelchair-bound at age 12 years. There was spinal rigidity, scoliosis, and kyphosis, as well as follicular hyperkeratosis, keloid formation, and need for nocturnal ventilation. The second patient had onset at age 1.5 years but never achieved independent walking and was wheelchair-bound by age 3.5 years. This patient died at age 10 years during a respiratory illness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19564581" 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 BETHLEM MYOPATHY 1C, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
COL6A3, IVS15DS, GT-TC, +1
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV003764591" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003764591" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003764591</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 40-year-old Australian man with Bethlem myopathy (BTHLM1C; <a href="/entry/620726">620726</a>), <a href="#1" class="mim-tip-reference" title="Baker, N. L., Morgelin, M., Pace, R. A., Peat, R. A., Adams, N. E., Gardner, R. J. M., Rowland, L. P., Miller, G., De Jonghe, P., Ceulemans, B., Hannibal, M. C., Edwards, M., Thompson, E. M., Jacobson, R., Quinlivan, R. C. M., Aftimos, S., Kornberg, A. J., North, K. N., Bateman, J. F., Lamande, S. R. <strong>Molecular consequences of dominant Bethlem myopathy collagen VI mutations.</strong> Ann. Neurol. 62: 390-405, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17886299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17886299</a>] [<a href="https://doi.org/10.1002/ana.21213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17886299">Baker et al. (2007)</a> identified a heterozygous 2-bp change (GT-to-TC) in intron 15 of the COL6A3 gene, resulting in the skipping of exon 16, which encodes the cysteine-rich linker region and the most N-terminal 15 amino acids of the triple helix. Further studies showed that the mutation also resulted in a premature stop codon and nonsense-mediated decay. There was decreased collagen VI in the extracellular matrix, indicating impaired microfibril formation. The patient had delayed motor development, diffuse muscle weakness, decreased motor capacity, kyphosis, and dystrophic features on muscle biopsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17886299" 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 BETHLEM MYOPATHY 1C, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
COL6A3, LEU1726ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121434555 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434555;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=rs121434555" 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=rs121434555" 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=RCV003764592" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003764592" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003764592</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 20-year-old man with Bethlem myopathy (BTHLM1C; <a href="/entry/620726">620726</a>), <a href="#1" class="mim-tip-reference" title="Baker, N. L., Morgelin, M., Pace, R. A., Peat, R. A., Adams, N. E., Gardner, R. J. M., Rowland, L. P., Miller, G., De Jonghe, P., Ceulemans, B., Hannibal, M. C., Edwards, M., Thompson, E. M., Jacobson, R., Quinlivan, R. C. M., Aftimos, S., Kornberg, A. J., North, K. N., Bateman, J. F., Lamande, S. R. <strong>Molecular consequences of dominant Bethlem myopathy collagen VI mutations.</strong> Ann. Neurol. 62: 390-405, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17886299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17886299</a>] [<a href="https://doi.org/10.1002/ana.21213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17886299">Baker et al. (2007)</a> identified a heterozygous 5177T-G transversion in a highly conserved residue in exon 11 of the COL6A3 gene, resulting in a leu1726-to-arg (L1726R) substitution in the globular N2 A domain. The patient had reduced motor capacity, proximal muscle weakness, joint contractures, and dystrophic findings on muscle biopsy. Further studies showed normal levels of collagen VI in the extracellular matrix, indicating that the mutant protein was able to fold and incorporate into collagen VI. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17886299" 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 DYSTONIA 27</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
COL6A3, ARG3043HIS (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs552651651;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs552651651</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> rs552651651 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs552651651;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/rs552651651?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=rs552651651" 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=rs552651651" 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=RCV000172849 OR RCV000277291 OR RCV000374757 OR RCV000653630 OR RCV001082877 OR RCV002227451 OR RCV004552949" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000172849, RCV000277291, RCV000374757, RCV000653630, RCV001082877, RCV002227451, RCV004552949" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000172849...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs, born of unrelated German parents, with dystonia-27 (DYT27; <a href="/entry/616411">616411</a>), <a href="#18" class="mim-tip-reference" title="Zech, M., Lam, D. D., Francescatto, L., Schormair, B., Salminen, A. V., Jochim, A., Wieland, T., Lichtner, P., Peters, A., Gieger, C., Lochmuller, H., Strom, T. M., Haslinger, B., Katsanis, N., Winkelmann, J. <strong>Recessive mutations in the alpha-3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia.</strong> Am. J. Hum. Genet. 96: 883-893, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26004199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26004199</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26004199[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.ajhg.2015.04.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26004199">Zech et al. (2015)</a> identified compound heterozygous missense mutations in the COL6A3 gene: a c.9128G-A transition (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs552651651;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs552651651</a>) in exon 41, resulting in an arg3043-to-his (R3043H) substitution, and a c.9245C-G transversion in exon 42, resulting in a pro3082-to-arg (P3082R; <a href="#0008">120250.0008</a>) substitution. Both mutations occurred at highly conserved residues in the C-terminal fibronectin type III motif (C4 domain). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The c.9128G-A variant was not found in the Exome Sequencing Project (ESP) database, whereas the c.9245C-G variant was found in 8 of 8,600 ESP alleles (frequency of 0.0009). Analysis of the Exome Aggregation Consortium database identified the 2 variants at very low frequencies (0.0003 for c.9128G-A and 0.001 for c.9245C-G). Notably, homozygosity for both variants was reported in 2 South Asian control exomes, suggesting either reduced penetrance or the possibility that these individuals may develop dystonia. Functional studies of the variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26004199" 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 DYSTONIA 27</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
COL6A3, PRO3082ARG (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs182976977;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs182976977</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> rs182976977 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs182976977;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/rs182976977?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=rs182976977" 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=rs182976977" 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=RCV000172850 OR RCV000272249 OR RCV000403938 OR RCV000653631 OR RCV001310783 OR RCV004725024" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000172850, RCV000272249, RCV000403938, RCV000653631, RCV001310783, RCV004725024" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000172850...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.9245C-G transversion (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs182976977;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs182976977</a>) in the COL6A3 gene, resulting in a pro3082-to-arg (P3082R) substitution, that was found in compound heterozygous state in a patient with dystonia-27 (DYT27; <a href="/entry/616411">616411</a>) by <a href="#18" class="mim-tip-reference" title="Zech, M., Lam, D. D., Francescatto, L., Schormair, B., Salminen, A. V., Jochim, A., Wieland, T., Lichtner, P., Peters, A., Gieger, C., Lochmuller, H., Strom, T. M., Haslinger, B., Katsanis, N., Winkelmann, J. <strong>Recessive mutations in the alpha-3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia.</strong> Am. J. Hum. Genet. 96: 883-893, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26004199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26004199</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26004199[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.ajhg.2015.04.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26004199">Zech et al. (2015)</a>, see <a href="#0007">120250.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26004199" 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 DYSTONIA 27</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
COL6A3, IVS40DS, G-C, -1
|
|
</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> rs767517186 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs767517186;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/rs767517186?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=rs767517186" 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=rs767517186" 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=RCV000172851 OR RCV000592070 OR RCV000688238" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000172851, RCV000592070, RCV000688238" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000172851...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 patients with dystonia-27 (DYT27; <a href="/entry/616411">616411</a>), <a href="#18" class="mim-tip-reference" title="Zech, M., Lam, D. D., Francescatto, L., Schormair, B., Salminen, A. V., Jochim, A., Wieland, T., Lichtner, P., Peters, A., Gieger, C., Lochmuller, H., Strom, T. M., Haslinger, B., Katsanis, N., Winkelmann, J. <strong>Recessive mutations in the alpha-3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia.</strong> Am. J. Hum. Genet. 96: 883-893, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26004199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26004199</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26004199[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.ajhg.2015.04.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26004199">Zech et al. (2015)</a> identified compound heterozygous mutations in the COL6A3 gene: both patients carried a G-to-C transversion in intron 40 (c.8966-1G-C, NM_004369.3), resulting in the skipping of exon 41 and an in-frame deletion of 98 residues from the C4 domain (Val2989_Lys3077delinsGlu). One patient carried a c.7502G-A transition resulting in an arg2501-to-his (R2501H; <a href="#0010">120250.0010</a>) substitution on the other allele, whereas the other patient carried a c.7660G-A transition, resulting in an ala2554-to-thr (A2554T; <a href="#0011">120250.0011</a>) substitution on the other allele. The c.7502G-A and c.7660G-A transitions occurred in exon 36 and affected highly conserved residues. None of the 3 variants were found in the Exome Sequencing Project database or in 752 control alleles. The c.8966-1G-C and c.7502G-A variants were found at very low frequencies in the Exome Aggregation Consortium (0.00003 and 0.00001, respectively); c.7660G-A was not found in this database. Functional studies of the variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26004199" 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 DYSTONIA 27</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
COL6A3, ARG2501HIS (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs541928674;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs541928674</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> rs541928674 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs541928674;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/rs541928674?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=rs541928674" 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=rs541928674" 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=RCV000172852 OR RCV000389218 OR RCV001372713" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000172852, RCV000389218, RCV001372713" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000172852...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.7502G-A transition (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs541928674;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs541928674</a>) in the COL6A3 gene, resulting in an arg2501-to-his (R2501H) substitution, that was found in compound heterozygous state in a patient with dystonia-27 (DYT27; <a href="/entry/616411">616411</a>) by <a href="#18" class="mim-tip-reference" title="Zech, M., Lam, D. D., Francescatto, L., Schormair, B., Salminen, A. V., Jochim, A., Wieland, T., Lichtner, P., Peters, A., Gieger, C., Lochmuller, H., Strom, T. M., Haslinger, B., Katsanis, N., Winkelmann, J. <strong>Recessive mutations in the alpha-3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia.</strong> Am. J. Hum. Genet. 96: 883-893, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26004199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26004199</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26004199[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.ajhg.2015.04.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26004199">Zech et al. (2015)</a>, see <a href="#0009">120250.0009</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26004199" 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 DYSTONIA 27</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
COL6A3, ALA2554THR
|
|
</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> rs786205870 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205870;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/rs786205870?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=rs786205870" 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=rs786205870" 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=RCV000172848 OR RCV000699713 OR RCV001198487 OR RCV004719736" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000172848, RCV000699713, RCV001198487, RCV004719736" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000172848...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.7660G-A transition (c.7660G-A, NM_004369.3) in the COL6A3 gene, resulting in an ala2554-to-thr (A2554T) substitution, that was found in compound heterozygous state in a patient with dystonia-27 (DYT27; <a href="/entry/616411">616411</a>) by <a href="#18" class="mim-tip-reference" title="Zech, M., Lam, D. D., Francescatto, L., Schormair, B., Salminen, A. V., Jochim, A., Wieland, T., Lichtner, P., Peters, A., Gieger, C., Lochmuller, H., Strom, T. M., Haslinger, B., Katsanis, N., Winkelmann, J. <strong>Recessive mutations in the alpha-3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia.</strong> Am. J. Hum. Genet. 96: 883-893, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26004199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26004199</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26004199[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.ajhg.2015.04.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26004199">Zech et al. (2015)</a>, see <a href="#0009">120250.0009</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26004199" 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 BETHLEM MYOPATHY 1C, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
COL6A3, LYS2483GLU (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs139260335;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs139260335</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> rs139260335 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs139260335;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/rs139260335?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=rs139260335" 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=rs139260335" 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=RCV000177877 OR RCV000352490 OR RCV003114326 OR RCV003387788 OR RCV004589832 OR RCV004783757" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000177877, RCV000352490, RCV003114326, RCV003387788, RCV004589832, RCV004783757" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000177877...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers (P9A and P9B) with variable manifestations of autosomal recessive Bethlem myopathy-1C (BTHLM1C; <a href="/entry/620726">620726</a>), <a href="#12" class="mim-tip-reference" title="Panades-de Oliveira, L., Rodriguez-Lopez, C., Cantero Montenegro, D., Marcos Toledano, M. D. M., Fernandez-Marmiesse, A., Esteban Perez, J., Hernandez Lain, A., Dominguez-Gonzalez, C. <strong>Bethlem myopathy: a series of 16 patients and description of seven new associated mutations.</strong> J. Neurol. 266: 934-941, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30706156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30706156</a>] [<a href="https://doi.org/10.1007/s00415-019-09217-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30706156">Panades-de Oliveira et al. (2019)</a> identified a homozygous c.7447A-G transition (c.7447A-G, NM_004369.3) in exon 36 of the COL6A3 gene, resulting in a lys2483-to-glu (K2483E) substitution. (In the article by <a href="#12" class="mim-tip-reference" title="Panades-de Oliveira, L., Rodriguez-Lopez, C., Cantero Montenegro, D., Marcos Toledano, M. D. M., Fernandez-Marmiesse, A., Esteban Perez, J., Hernandez Lain, A., Dominguez-Gonzalez, C. <strong>Bethlem myopathy: a series of 16 patients and description of seven new associated mutations.</strong> J. Neurol. 266: 934-941, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30706156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30706156</a>] [<a href="https://doi.org/10.1007/s00415-019-09217-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30706156">Panades-de Oliveira et al. (2019)</a>, this variant is incorrectly cited as lys2486-to-glu (K2486E) in the abstract and at various places in the text, but correctly as K2483E in Table 2 and at other places in the text.) Another patient (P8A) with the disorder was compound heterozygous for K2483E and a 1-bp deletion (c.8540delA; <a href="#0013">120250.0013</a>) in exon 39, predicted to result in a frameshift and premature termination. The mutations were found by next-generation sequencing and confirmed by Sanger sequencing. Functional studies of the variants and studies of patient cells were not performed. P9A, a 42-year-old man, had onset of proximal muscle weakness in childhood, whereas his brother (P9B) was almost asymptomatic at 48 years of age, except for hyperCKemia and distal contractures. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30706156" 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 16 patients from 14 families with autosomal recessive Bethlem myopathy-1C (BTHLM1C; <a href="/entry/620726">620726</a>), <a href="#15" class="mim-tip-reference" title="Villar-Quiles, R. N., Donkervoort, S., de Becdelievre, A., Gartioux, C., Jobic, V., Foley, A. R., McCarty, R. M., Hu, Y., Menassa, R., Michel, L., Gousse, G., Lacour, A., and 20 others. <strong>Clinical and molecular spectrum associated with COL6A3 c.7447A-G p.(Lys2483Glu) variant: elucidating its role in collagen VI-related myopathies.</strong> J. Neuromusc. Dis. 8: 633-645, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33749658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33749658</a>] [<a href="https://doi.org/10.3233/JND-200577" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33749658">Villar-Quiles et al. (2021)</a> identified a c.7447A-G transition in the COL6A3 gene, resulting in a lys2483-to-glu (K2483E) substitution in a nonhelical domain. Twelve patients carried the variant in compound heterozygosity with another putative loss-of-function variant in the COL6A3 gene (see, e.g., R1597X, <a href="#0014">120250.0014</a>), whereas 4 patients (P11, P12, P13, and P14) were homozygous for the K2483E variant. Segregation studies performed in 8 families confirmed that the tested parents were unaffected heterozygous carriers. Fibroblasts derived from 5 of the compound heterozygous patients showed reduced collagen VI secretion, which was most likely due to the second loss-of-function COL6A3 variant. In contrast, fibroblasts from 3 patients who were homozygous for the K2483E variant showed essentially normal collagen VI secretion in 2 and mildly reduced secretion in 1, suggesting that the missense variant does not significantly impact COL6 assembly and secretion. <a href="#15" class="mim-tip-reference" title="Villar-Quiles, R. N., Donkervoort, S., de Becdelievre, A., Gartioux, C., Jobic, V., Foley, A. R., McCarty, R. M., Hu, Y., Menassa, R., Michel, L., Gousse, G., Lacour, A., and 20 others. <strong>Clinical and molecular spectrum associated with COL6A3 c.7447A-G p.(Lys2483Glu) variant: elucidating its role in collagen VI-related myopathies.</strong> J. Neuromusc. Dis. 8: 633-645, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33749658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33749658</a>] [<a href="https://doi.org/10.3233/JND-200577" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33749658">Villar-Quiles et al. (2021)</a> suggested that this missense variant may act as a modulator of the clinical phenotype. The 12 patients who were compound heterozygous for K2483E and another COL6A3 variant tended to present in childhood with proximal muscle weakness, joint contractures, and variable presence of rigid spine, skin abnormalities, and mild respiratory involvement. In contrast, the patients who were homozygous for the K2483E variant had fewer joint contractures, and none had distal hyperlaxity, skin abnormalities, or respiratory involvement. <a href="#5" class="mim-tip-reference" title="Hamosh, A. <strong>Personal Communication.</strong> Baltimore, Md. 7/10/2024."None>Hamosh (2024)</a> noted that the K2483E variant was present in heterozygous state in 1,158 of 1,614,090 alleles in gnomAD (v4.1.0) and in 1 homozygote (frequency of 7.0 x 10(-4)). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33749658" 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 BETHLEM MYOPATHY 1C, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
COL6A3, 1-BP DEL, 8540A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV004588598" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV004588598" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV004588598</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp deletion (c.8540delA) in exon 39 of the COL6A3 gene, predicted to result in a frameshift and premature termination, that was found in compound heterozygous state in a patient (P8A) with autosomal recessive Bethlem myopathy-1C (BTHLM1C; <a href="/entry/620726">620726</a>) by <a href="#12" class="mim-tip-reference" title="Panades-de Oliveira, L., Rodriguez-Lopez, C., Cantero Montenegro, D., Marcos Toledano, M. D. M., Fernandez-Marmiesse, A., Esteban Perez, J., Hernandez Lain, A., Dominguez-Gonzalez, C. <strong>Bethlem myopathy: a series of 16 patients and description of seven new associated mutations.</strong> J. Neurol. 266: 934-941, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30706156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30706156</a>] [<a href="https://doi.org/10.1007/s00415-019-09217-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30706156">Panades-de Oliveira et al. (2019)</a>, see <a href="#0012">120250.0012</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30706156" 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 BETHLEM MYOPATHY 1C, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
COL6A3, ARG1597TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV004554350 OR RCV004595715" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV004554350, RCV004595715" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV004554350...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.4789C-T transition in the COL6A3 gene, resulting in an arg1597-to-ter (R1597X) substitution, that was found in compound heterozygous state in 2 sibs (family 1) with autosomal recessive Bethlem myopathy-1C (BTHLM1C; <a href="/entry/620726">620726</a>) by <a href="#15" class="mim-tip-reference" title="Villar-Quiles, R. N., Donkervoort, S., de Becdelievre, A., Gartioux, C., Jobic, V., Foley, A. R., McCarty, R. M., Hu, Y., Menassa, R., Michel, L., Gousse, G., Lacour, A., and 20 others. <strong>Clinical and molecular spectrum associated with COL6A3 c.7447A-G p.(Lys2483Glu) variant: elucidating its role in collagen VI-related myopathies.</strong> J. Neuromusc. Dis. 8: 633-645, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33749658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33749658</a>] [<a href="https://doi.org/10.3233/JND-200577" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33749658">Villar-Quiles et al. (2021)</a>, see <a href="#0012">120250.0012</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33749658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Baker2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Baker, N. L., Morgelin, M., Pace, R. A., Peat, R. A., Adams, N. E., Gardner, R. J. M., Rowland, L. P., Miller, G., De Jonghe, P., Ceulemans, B., Hannibal, M. C., Edwards, M., Thompson, E. M., Jacobson, R., Quinlivan, R. C. M., Aftimos, S., Kornberg, A. J., North, K. N., Bateman, J. F., Lamande, S. R.
|
|
<strong>Molecular consequences of dominant Bethlem myopathy collagen VI mutations.</strong>
|
|
Ann. Neurol. 62: 390-405, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17886299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17886299</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17886299" 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.21213" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Baker2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Baker, N. L., Morgelin, M., Peat, R., Goemans, N., North, K. N., Bateman, J. F., Lamande, S. R.
|
|
<strong>Dominant collagen VI mutations are a common cause of Ullrich congenital muscular dystrophy.</strong>
|
|
Hum. Molec. Genet. 14: 279-293, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15563506/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15563506</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15563506" 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/ddi025" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Chu1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chu, M.-L., Zhang, R.-Z., Pan, T.-C., Stokes, D., Conway, D., Kuo, H.-J., Glanville, R., Mayer, U., Mann, K., Deutzmann, R., Timpl, R.
|
|
<strong>Mosaic structure of globular domains in the human type VI collagen alpha-3 chain: similarity to von Willebrand factor, fibronectin, actin, salivary proteins and apotinin type protease inhibitors.</strong>
|
|
EMBO J. 9: 385-393, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1689238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1689238</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1689238" 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.1460-2075.1990.tb08122.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Demir2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Demir, E., Sabatelli, P., Allamand, V., Ferreiro, A., Moghadaszadeh, B., Makrelouf, M., Topaloglu, H., Echenne, B., Merlini, E., Guicheney, P.
|
|
<strong>Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy.</strong>
|
|
Am. J. Hum. Genet. 70: 1446-1458, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11992252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11992252</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11992252[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=11992252" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/340608" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Hamosh2024" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hamosh, A.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 7/10/2024.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Jun2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jun, A. S., Liu, S. H., Koo, E. H., Do, D. V., Stark, W. J., Gottsch, J. D.
|
|
<strong>Microarray analysis of gene expression in human donor corneas.</strong>
|
|
Arch. Ophthal. 119: 1629-1634, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709013/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709013</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709013" 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/archopht.119.11.1629" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Klewer1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Klewer, S. E., Krob, S. L., Kolker, S. J., Kitten, G. T.
|
|
<strong>Expression of type VI collagen in the developing mouse heart.</strong>
|
|
Dev. Dyn. 211: 248-255, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9520112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9520112</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9520112" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1097-0177(199803)211:3<248::AID-AJA6>3.0.CO;2-H" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Lampe2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lampe, A. K., Dunn, D. M., von Niederhausern, A. C., Hamil, C., Aoyagi, A., Laval, S. H., Marie, S. K., Chu, M.-L., Swoboda, K., Muntoni, F., Bonnemann, C. G., Flanigan, K. M., Bushby, K. M. D., Weiss, R. B.
|
|
<strong>Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy.</strong>
|
|
J. Med. Genet. 42: 108-120, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15689448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15689448</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15689448" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2004.023754" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Mohire1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mohire, M. D., Tandan, R., Fries, T. J., Little, B. W., Pendlebury, W. W., Bradley, W. G.
|
|
<strong>Early-onset benign autosomal dominant limb-girdle myopathy with contractures (Bethlem myopathy).</strong>
|
|
Neurology 38: 573-580, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3352914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3352914</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3352914" 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.38.4.573" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Nadeau2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nadeau, A., Kinali, M., Main, M., Jimenez-Mallebrera, C., Aloysius, A., Clement, E., North, B., Manzur, A. Y., Robb, S. A., Mercuri, E., Muntoni, F.
|
|
<strong>Natural history of Ullrich congenital muscular dystrophy.</strong>
|
|
Neurology 73: 25-31, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19564581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19564581</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19564581" 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.0b013e3181aae851" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Pan1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pan, T.-C., Zhang, R.-Z., Pericak-Vance, M. A., Tandan, R., Fries, T., Stajich, J. M., Viles, K., Vance, J. M., Chu, M.-L., Speer, M. C.
|
|
<strong>Missense mutation in a von Willebrand factor type A domain of the alpha-3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy.</strong>
|
|
Hum. Molec. Genet. 7: 807-812, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9536084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9536084</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9536084" 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/7.5.807" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Panades-de Oliveira2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Panades-de Oliveira, L., Rodriguez-Lopez, C., Cantero Montenegro, D., Marcos Toledano, M. D. M., Fernandez-Marmiesse, A., Esteban Perez, J., Hernandez Lain, A., Dominguez-Gonzalez, C.
|
|
<strong>Bethlem myopathy: a series of 16 patients and description of seven new associated mutations.</strong>
|
|
J. Neurol. 266: 934-941, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30706156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30706156</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30706156" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s00415-019-09217-z" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Speer1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Speer, M. C., Tandan, R., Rao, P. N., Fries, T., Stajich, J. M., Bolhuis, P. A., Jobsis, G. J., Vance, J. M., Viles, K. D., Sheffield, K., James, C., Kahler, S. G., Pettenati, M., Gilbert, J. R., Denton, P. H., Yamaoka, L. H., Pericak-Vance, M. A.
|
|
<strong>Evidence for locus heterogeneity in the Bethlem myopathy and linkage to 2q37.</strong>
|
|
Hum. Molec. Genet. 5: 1043-1046, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8817344/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8817344</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8817344" 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/5.7.1043" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Stokes1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stokes, D. G., Saitta, B., Timpl, R., Chu, M.-L.
|
|
<strong>Human alpha-3(VI) collagen gene: characterization of exons coding for the amino-terminal globular domain and alternative splicing in normal and tumor cells.</strong>
|
|
J. Biol. Chem. 266: 8626-8633, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2022673/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2022673</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2022673" 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="Villar-Quiles2021" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Villar-Quiles, R. N., Donkervoort, S., de Becdelievre, A., Gartioux, C., Jobic, V., Foley, A. R., McCarty, R. M., Hu, Y., Menassa, R., Michel, L., Gousse, G., Lacour, A., and 20 others.
|
|
<strong>Clinical and molecular spectrum associated with COL6A3 c.7447A-G p.(Lys2483Glu) variant: elucidating its role in collagen VI-related myopathies.</strong>
|
|
J. Neuromusc. Dis. 8: 633-645, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33749658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33749658</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33749658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.3233/JND-200577" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Weil1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weil, D., Mattei, M.-G., Passage, E., Van Cong, N., Pribula-Conway, D., Mann, K., Deutzmann, R., Timpl, R., Chu, M.-L.
|
|
<strong>Assignment of the three genes coding for the different chains of type VI collagen (COL6A1, COL6A2, COL6A3). (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 46: 713 only, 1987.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Weil1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weil, D., Mattei, M.-G., Passage, E., Van Cong, N., Pribula-Conway, D., Mann, K., Deutzmann, R., Timpl, R., Chu, M.-L.
|
|
<strong>Cloning and chromosomal localization of human genes encoding the three chains of type VI collagen.</strong>
|
|
Am. J. Hum. Genet. 42: 435-445, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3348212/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3348212</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3348212" 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="18" class="mim-anchor"></a>
|
|
<a id="Zech2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zech, M., Lam, D. D., Francescatto, L., Schormair, B., Salminen, A. V., Jochim, A., Wieland, T., Lichtner, P., Peters, A., Gieger, C., Lochmuller, H., Strom, T. M., Haslinger, B., Katsanis, N., Winkelmann, J.
|
|
<strong>Recessive mutations in the alpha-3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia.</strong>
|
|
Am. J. Hum. Genet. 96: 883-893, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26004199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26004199</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26004199[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=26004199" 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.ajhg.2015.04.010" 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 : 07/10/2024
|
|
</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">
|
|
Hamosh, A.: - updated : 07/10/2024<br>Cassandra L. Kniffin - updated : 6/4/2015<br>Cassandra L. Kniffin - updated : 12/15/2009<br>Cassandra L. Kniffin - updated : 5/23/2008<br>George E. Tiller - updated : 11/8/2007<br>Marla J. F. O'Neill - updated : 3/1/2005<br>Jane Kelly - updated : 12/6/2002<br>Victor A. McKusick - updated : 6/11/2002<br>Victor A. McKusick - updated : 5/22/1998<br>Paul Brennan - updated : 5/14/1998<br>Mark H. Paalman - updated : 8/15/1996
|
|
</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 : 2/9/1987
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 07/15/2024
|
|
</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">
|
|
carol : 07/15/2024<br>ckniffin : 07/10/2024<br>carol : 06/06/2024<br>ckniffin : 06/05/2024<br>carol : 02/29/2024<br>carol : 02/22/2024<br>carol : 02/21/2024<br>carol : 02/20/2024<br>carol : 07/20/2015<br>joanna : 6/16/2015<br>carol : 6/5/2015<br>mcolton : 6/5/2015<br>ckniffin : 6/4/2015<br>mcolton : 3/3/2015<br>carol : 12/23/2009<br>ckniffin : 12/15/2009<br>wwang : 7/8/2008<br>ckniffin : 7/2/2008<br>ckniffin : 5/23/2008<br>wwang : 11/30/2007<br>terry : 11/8/2007<br>wwang : 3/14/2005<br>wwang : 3/8/2005<br>terry : 3/1/2005<br>carol : 12/6/2002<br>alopez : 6/13/2002<br>terry : 6/11/2002<br>terry : 6/11/2002<br>dkim : 12/9/1998<br>terry : 6/3/1998<br>terry : 5/22/1998<br>carol : 5/14/1998<br>terry : 9/5/1996<br>terry : 9/3/1996<br>terry : 8/16/1996<br>mark : 8/15/1996<br>mark : 8/15/1996<br>carol : 10/7/1994<br>supermim : 3/16/1992<br>carol : 7/24/1991<br>carol : 7/12/1991<br>supermim : 3/20/1990<br>ddp : 10/26/1989
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="container visible-print-block">
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
<div class="col-md-8 col-md-offset-1">
|
|
|
|
<div>
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>*</strong> 120250
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
COLLAGEN, TYPE VI, ALPHA-3; COL6A3
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: COL6A3</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 1220573009;
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 2q37.3
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 2:237,324,018-237,414,164 </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="3">
|
|
<span class="mim-font">
|
|
2q37.3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Bethlem myopathy 1C
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
620726
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant; Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Dystonia 27
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
616411
|
|
</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">
|
|
Ullrich congenital muscular dystrophy 1C
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
620728
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant; Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The COL6A3 gene encodes the alpha-3 chain of type VI collagen. See also COL6A1 (120220).</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>Chu et al. (1990) isolated and sequenced human cDNA clones corresponding to the COL6A3 gene. </p><p>Klewer et al. (1998) studied COL6A3 gene expression in the developing mammalian heart. The pattern of expression was identical to that of COL6A1. </p><p>By microarray analysis, Jun et al. (2001) demonstrated expression of the COL6A3 gene in human donor corneas. </p><p>Zech et al. (2015) found expression of the Col6a3 gene in neurons of the mouse brain, including in the cerebellum and striatum, with highest expression in the brainstem and midbrain. Astroglia did not express Col6a3. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Stokes et al. (1991) reported information on the exons for part of the COL6A3 gene. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Weil et al. (1987, 1988) localized the COL6A3 gene to chromosome 2q37 by Southern blot analysis of somatic cell hybrids and by in situ hybridization. At least 3 other extracellular matrix genes are also located on 2q: 2 collagen genes, COL3A1 (120180) and COL5A2 (120190), and the fibronectin gene (135600). </p><p>Using fluorescence in situ hybridization, Speer et al. (1996) localized the COL6A3 gene to chromosome 2q37 within a 17-cM region spanned by D2S336 and D2S395. By linkage analysis, they mapped a candidate gene for Bethlem myopathy (620726) to the same chromosomal region. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Bethlem Myopathy 1C and Ullrich Congenital Muscular Dystrophy 1C</em></strong></p><p>
|
|
Pan et al. (1998) identified a heterozygous mutation in the COL6A3 gene (120250.0001) in affected members of a large American pedigree of French Canadian descent (family 1949) with Bethlem myopathy-1C (BTHLM1C; 620726), a rare proximal myopathy characterized by early childhood onset and joint contractures. The mutation segregated with the disorder in the family, which was originally reported by Mohire et al. (1988). </p><p>In 2 unrelated patients with Bethlem myopathy, Baker et al. (2007) identified different heterozygous mutations in the COL6A3 gene (120250.0005; 120250.0006). </p><p>Ullrich congenital muscular dystrophy-1C (UCMD1C; 620728) is characterized by generalized muscular weakness, contractures of multiple joints, and distal hyperextensibility. Demir et al. (2002) demonstrated linkage of UCMD to 2q37 in 3 families, each of which demonstrated homozygous mutation in the COL6A3 gene (see, e.g., 120250.0002 and 120250.0003). One family (family I) had a phenotype of intermediate severity, a second (family II) had an unusually mild phenotype, and a third (family III) had a severe phenotype as previously described in patients with UCMD. This was the first description of mutations in COL6A3 in UCMD; mutations had previously been described in COL6A2 (120240). </p><p>Lampe et al. (2005) developed a method for rapid direct sequence analysis of all 107 coding exons of the COL6 genes (COL6A1, COL6A2, COL6A3) using single condition amplification/internal primer (SCAIP) sequencing. They sequenced all 3 COL6 genes from genomic DNA in 79 patients with UCMD or Bethlem myopathy, and found putative mutations in one of the COL6 genes in 62% of patients. Some patients showed changes in more than one of the COL6 genes, and some UCMD patients appeared to have dominant rather than recessive disease. Lampe et al. (2005) concluded that these findings may explain some or all of the cases of UCMD that are unlinked to the COL6 genes under a recessive model. </p><p>Nadeau et al. (2009) identified a recurrent de novo heterozygous splice site mutation in the COL6A3 gene (120250.0004) in 2 unrelated individuals with UCMD1C. </p><p>In 2 brothers (P9A and P9B) with variable manifestations of autosomal recessive Bethlem myopathy-1C (BTHLM1C; 620726), Panades-de Oliveira et al. (2019) identified a homozygous missense variant in the COL6A3 gene (K2483E; 120250.0012). Another patient (P8A) with the disorder was compound heterozygous for K2483E and a frameshift mutation (c.8540delA; 120250.0013). The mutations were found by next-generation sequencing and confirmed by Sanger sequencing. Functional studies of the variants and studies of patient cells were not performed. P9A, a 42-year-old man, had onset of proximal muscle weakness in childhood, whereas his brother (P9B) was almost asymptomatic at 48 years of age, except for hyperCKemia and distal contractures. </p><p>Villar-Quiles et al. (2021) reported 16 patients with autosomal recessive BTHLM1C associated with the K2483E substitution in the COL6A3 gene (120250.0012). Four unrelated patients were homozygous for the mutation, and 12 patients from 10 families carried it in the compound heterozygous state with another putative loss-of-function COL6A3 mutation (see, e.g., R1597X, 120250.0014). Segregation studies, performed in 8 families, confirmed that the unaffected parents were heterozygous carriers. Fibroblasts derived from 5 of the compound heterozygous patients showed reduced collagen VI secretion, which was most likely due to the second loss-of-function COL6A3 variant. In contrast, fibroblasts from 3 patients who were homozygous for the K2483E variant showed essentially normal collagen VI secretion in 2 and mildly reduced secretion in 1, suggesting that the missense variant does not significantly impact COL6 assembly and secretion. Villar-Quiles et al. (2021) suggested that this missense variant may act as a modulator of the clinical phenotype. </p><p><strong><em>Dystonia 27</em></strong></p><p>
|
|
In affected members of 3 unrelated German families with autosomal recessive dystonia-27 (DYT27; 616411), Zech et al. (2015) identified compound heterozygous mutations in the COL6A3 gene (120250.0007-120250.0011) that segregated with the disorder in each family. The mutations in the first family were found by exome sequencing; mutations in the subsequent 2 families were found by sequencing exons 41 and 42 of the COL6A3 gene in 367 German cases with isolated dystonia. All patients carried mutations affecting the C terminus, with at least 1 mutation specifically affecting exon 41. The patients presented before age 25 years with isolated dystonia mainly affecting the craniocervical region and the upper limbs. None of the patients had signs of muscular involvement, and patient fibroblasts showed normal distribution and organization of collagen VI. Functional studies of the variants were not performed, but selective knockdown of the zebrafish ortholog resulted in axonal targeting defects. Zech et al. (2015) hypothesized that perturbation of the brain extracellular matrix may underlie this form of dystonia. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Zech et al. (2015) found that morpholino knockdown of exon 42 of the zebrafish col6a3 gene, which corresponds to exon 41 of the human COL6A3 gene, caused dose-dependent motor neuron pathfinding, branching, and extension errors without overt collagen defects. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>14 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 BETHLEM MYOPATHY 1C, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL6A3, GLY1679GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121434553,
|
|
|
|
|
|
|
|
ClinVar: RCV000018689, RCV000790696, RCV003764588
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a large American kindred of French Canadian descent (family 1489) with Bethlem myopathy (BTHLM1C; 620726), originally reported by Mohire et al. (1988) and linked to chromosome 2 by Speer et al. (1996), Pan et al. (1998) identified a heterozygous G-to-A transition in the COL6A3 gene, resulting in a gly1679-to-glu (G1679E) substitution in the N-terminal globular domain of the protein, rather than in the triple-helical domain where mutations had been found in the COL6A1 (120220) and COL6A2 (120240) genes. The mutation occurred in the N2 subdomain, one of the von Willebrand factor type A domains of the COL6A3 gene. The mutation segregated with the disorder in the family. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 ULLRICH CONGENITAL MUSCULAR DYSTROPHY 1C, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL6A3, IVS29, A-G, +5
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs749037028,
|
|
|
|
|
|
gnomAD: rs749037028,
|
|
|
|
|
|
ClinVar: RCV000018690, RCV003517127, RCV003764589
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 sibs, a brother and 2 sisters, with consanguineous parents originating from Morocco (family I), Demir et al. (2002) identified homozygosity for a splice donor site mutation in intron 29 (c.6930+5A-G) as the cause of autosomal recessive Ullrich congenital muscular dystrophy (UCMD1C; 620728). The phenotype was of intermediate severity. The mutation caused skipping of exon 29 and partial reduction of collagen VI in muscle biopsy. Neonatal hypotonia, severe in most cases, was found in all 5 cases in the 3 families reported by Demir et al. (2002). In this family the 2 eldest sibs were never able to walk without support (calipers or walking frame). Generalized muscle weakness, associated with predominantly distal amyotrophy, became evident in the first years of life. Axial muscles (mainly neck flexors), pelvic girdle muscles, and intrinsic muscles in hands and feet were the most severely affected ones. Lower limbs tended to be more severely affected than upper limbs; in most cases, hip extensors and abductors were weaker than hip flexors, leading to hip contractures that interfered with standing position. No significant facial weakness was observed. CK levels were normal or moderately raised (up to 4 times the normal values). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 ULLRICH CONGENITAL MUSCULAR DYSTROPHY 1C, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL6A3, ARG465TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121434554,
|
|
|
|
|
|
|
|
ClinVar: RCV002247356, RCV003764590
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a girl of Italian extraction (family II) with unusually mild Ullrich congenital muscular dystrophy (UCMD1C; 620728), Demir et al. (2002) found a homozygous nonsense mutation in exon 5 of the COL6A3 gene: arg465 to ter (R465X). Analysis of the patient's COL6A3 transcript showed the presence of various mRNA species, one of which lacked several exons, including the exon containing the nonsense mutation. The patient in this case was still ambulant at age 18 and showed an unusual combination of hyperlaxity and finger contractures (see Figure 2). When the wrist was extended, the retraction of finger flexor muscles impeded complete finger extension, causing flexion contractures of fingers, which is regarded as a characteristic 'Bethlem' sign. When the wrist was not extended, the finger laxity became evident. The patient was able to overlap, cross, or extend fingers beyond the normal range of motion ('Ullrich sign'). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 ULLRICH CONGENITAL MUSCULAR DYSTROPHY 1C, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL6A3, IVS16DS, G-A, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs398124126,
|
|
|
|
|
|
|
|
ClinVar: RCV000080961, RCV000175056, RCV000817699, RCV003764764
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient (UCMD5) with Ullrich congenital muscular dystrophy (UCMD1C; 620728), Baker et al. (2005) identified heterozygosity for a de novo splice site mutation (IVS16DS+1G-A) in intron 16 of the COL6A3 gene. The mutation was predicted to result in loss of exon 16, which encodes amino acids 13 to 33 of the triple helical region of COL6A3. </p><p>Nadeau et al. (2009) identified a recurrent de novo heterozygous IVS16DS+1G-A mutation in 2 unrelated patients with UCMD1C. The first patient was a 30-year-old individual who had onset at birth with hypotonia, congenital hip dislocation, delayed motor development, and feeding difficulties. Independent walking was not achieved, and the patient became wheelchair-bound at age 12 years. There was spinal rigidity, scoliosis, and kyphosis, as well as follicular hyperkeratosis, keloid formation, and need for nocturnal ventilation. The second patient had onset at age 1.5 years but never achieved independent walking and was wheelchair-bound by age 3.5 years. This patient died at age 10 years during a respiratory illness. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 BETHLEM MYOPATHY 1C, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL6A3, IVS15DS, GT-TC, +1
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV003764591
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 40-year-old Australian man with Bethlem myopathy (BTHLM1C; 620726), Baker et al. (2007) identified a heterozygous 2-bp change (GT-to-TC) in intron 15 of the COL6A3 gene, resulting in the skipping of exon 16, which encodes the cysteine-rich linker region and the most N-terminal 15 amino acids of the triple helix. Further studies showed that the mutation also resulted in a premature stop codon and nonsense-mediated decay. There was decreased collagen VI in the extracellular matrix, indicating impaired microfibril formation. The patient had delayed motor development, diffuse muscle weakness, decreased motor capacity, kyphosis, and dystrophic features on muscle biopsy. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 BETHLEM MYOPATHY 1C, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL6A3, LEU1726ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121434555,
|
|
|
|
|
|
|
|
ClinVar: RCV003764592
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 20-year-old man with Bethlem myopathy (BTHLM1C; 620726), Baker et al. (2007) identified a heterozygous 5177T-G transversion in a highly conserved residue in exon 11 of the COL6A3 gene, resulting in a leu1726-to-arg (L1726R) substitution in the globular N2 A domain. The patient had reduced motor capacity, proximal muscle weakness, joint contractures, and dystrophic findings on muscle biopsy. Further studies showed normal levels of collagen VI in the extracellular matrix, indicating that the mutant protein was able to fold and incorporate into collagen VI. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 DYSTONIA 27</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL6A3, ARG3043HIS ({dbSNP rs552651651})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs552651651,
|
|
|
|
|
|
gnomAD: rs552651651,
|
|
|
|
|
|
ClinVar: RCV000172849, RCV000277291, RCV000374757, RCV000653630, RCV001082877, RCV002227451, RCV004552949
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sibs, born of unrelated German parents, with dystonia-27 (DYT27; 616411), Zech et al. (2015) identified compound heterozygous missense mutations in the COL6A3 gene: a c.9128G-A transition (rs552651651) in exon 41, resulting in an arg3043-to-his (R3043H) substitution, and a c.9245C-G transversion in exon 42, resulting in a pro3082-to-arg (P3082R; 120250.0008) substitution. Both mutations occurred at highly conserved residues in the C-terminal fibronectin type III motif (C4 domain). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The c.9128G-A variant was not found in the Exome Sequencing Project (ESP) database, whereas the c.9245C-G variant was found in 8 of 8,600 ESP alleles (frequency of 0.0009). Analysis of the Exome Aggregation Consortium database identified the 2 variants at very low frequencies (0.0003 for c.9128G-A and 0.001 for c.9245C-G). Notably, homozygosity for both variants was reported in 2 South Asian control exomes, suggesting either reduced penetrance or the possibility that these individuals may develop dystonia. Functional studies of the variants were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 DYSTONIA 27</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL6A3, PRO3082ARG ({dbSNP rs182976977})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs182976977,
|
|
|
|
|
|
gnomAD: rs182976977,
|
|
|
|
|
|
ClinVar: RCV000172850, RCV000272249, RCV000403938, RCV000653631, RCV001310783, RCV004725024
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.9245C-G transversion (rs182976977) in the COL6A3 gene, resulting in a pro3082-to-arg (P3082R) substitution, that was found in compound heterozygous state in a patient with dystonia-27 (DYT27; 616411) by Zech et al. (2015), see 120250.0007. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 DYSTONIA 27</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL6A3, IVS40DS, G-C, -1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs767517186,
|
|
|
|
|
|
gnomAD: rs767517186,
|
|
|
|
|
|
ClinVar: RCV000172851, RCV000592070, RCV000688238
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 patients with dystonia-27 (DYT27; 616411), Zech et al. (2015) identified compound heterozygous mutations in the COL6A3 gene: both patients carried a G-to-C transversion in intron 40 (c.8966-1G-C, NM_004369.3), resulting in the skipping of exon 41 and an in-frame deletion of 98 residues from the C4 domain (Val2989_Lys3077delinsGlu). One patient carried a c.7502G-A transition resulting in an arg2501-to-his (R2501H; 120250.0010) substitution on the other allele, whereas the other patient carried a c.7660G-A transition, resulting in an ala2554-to-thr (A2554T; 120250.0011) substitution on the other allele. The c.7502G-A and c.7660G-A transitions occurred in exon 36 and affected highly conserved residues. None of the 3 variants were found in the Exome Sequencing Project database or in 752 control alleles. The c.8966-1G-C and c.7502G-A variants were found at very low frequencies in the Exome Aggregation Consortium (0.00003 and 0.00001, respectively); c.7660G-A was not found in this database. Functional studies of the variants were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 DYSTONIA 27</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL6A3, ARG2501HIS ({dbSNP rs541928674})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs541928674,
|
|
|
|
|
|
gnomAD: rs541928674,
|
|
|
|
|
|
ClinVar: RCV000172852, RCV000389218, RCV001372713
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.7502G-A transition (rs541928674) in the COL6A3 gene, resulting in an arg2501-to-his (R2501H) substitution, that was found in compound heterozygous state in a patient with dystonia-27 (DYT27; 616411) by Zech et al. (2015), see 120250.0009. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 DYSTONIA 27</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL6A3, ALA2554THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs786205870,
|
|
|
|
|
|
gnomAD: rs786205870,
|
|
|
|
|
|
ClinVar: RCV000172848, RCV000699713, RCV001198487, RCV004719736
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.7660G-A transition (c.7660G-A, NM_004369.3) in the COL6A3 gene, resulting in an ala2554-to-thr (A2554T) substitution, that was found in compound heterozygous state in a patient with dystonia-27 (DYT27; 616411) by Zech et al. (2015), see 120250.0009. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 BETHLEM MYOPATHY 1C, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL6A3, LYS2483GLU ({dbSNP rs139260335})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs139260335,
|
|
|
|
|
|
gnomAD: rs139260335,
|
|
|
|
|
|
ClinVar: RCV000177877, RCV000352490, RCV003114326, RCV003387788, RCV004589832, RCV004783757
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers (P9A and P9B) with variable manifestations of autosomal recessive Bethlem myopathy-1C (BTHLM1C; 620726), Panades-de Oliveira et al. (2019) identified a homozygous c.7447A-G transition (c.7447A-G, NM_004369.3) in exon 36 of the COL6A3 gene, resulting in a lys2483-to-glu (K2483E) substitution. (In the article by Panades-de Oliveira et al. (2019), this variant is incorrectly cited as lys2486-to-glu (K2486E) in the abstract and at various places in the text, but correctly as K2483E in Table 2 and at other places in the text.) Another patient (P8A) with the disorder was compound heterozygous for K2483E and a 1-bp deletion (c.8540delA; 120250.0013) in exon 39, predicted to result in a frameshift and premature termination. The mutations were found by next-generation sequencing and confirmed by Sanger sequencing. Functional studies of the variants and studies of patient cells were not performed. P9A, a 42-year-old man, had onset of proximal muscle weakness in childhood, whereas his brother (P9B) was almost asymptomatic at 48 years of age, except for hyperCKemia and distal contractures. </p><p>In 16 patients from 14 families with autosomal recessive Bethlem myopathy-1C (BTHLM1C; 620726), Villar-Quiles et al. (2021) identified a c.7447A-G transition in the COL6A3 gene, resulting in a lys2483-to-glu (K2483E) substitution in a nonhelical domain. Twelve patients carried the variant in compound heterozygosity with another putative loss-of-function variant in the COL6A3 gene (see, e.g., R1597X, 120250.0014), whereas 4 patients (P11, P12, P13, and P14) were homozygous for the K2483E variant. Segregation studies performed in 8 families confirmed that the tested parents were unaffected heterozygous carriers. Fibroblasts derived from 5 of the compound heterozygous patients showed reduced collagen VI secretion, which was most likely due to the second loss-of-function COL6A3 variant. In contrast, fibroblasts from 3 patients who were homozygous for the K2483E variant showed essentially normal collagen VI secretion in 2 and mildly reduced secretion in 1, suggesting that the missense variant does not significantly impact COL6 assembly and secretion. Villar-Quiles et al. (2021) suggested that this missense variant may act as a modulator of the clinical phenotype. The 12 patients who were compound heterozygous for K2483E and another COL6A3 variant tended to present in childhood with proximal muscle weakness, joint contractures, and variable presence of rigid spine, skin abnormalities, and mild respiratory involvement. In contrast, the patients who were homozygous for the K2483E variant had fewer joint contractures, and none had distal hyperlaxity, skin abnormalities, or respiratory involvement. Hamosh (2024) noted that the K2483E variant was present in heterozygous state in 1,158 of 1,614,090 alleles in gnomAD (v4.1.0) and in 1 homozygote (frequency of 7.0 x 10(-4)). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 BETHLEM MYOPATHY 1C, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL6A3, 1-BP DEL, 8540A
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV004588598
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp deletion (c.8540delA) in exon 39 of the COL6A3 gene, predicted to result in a frameshift and premature termination, that was found in compound heterozygous state in a patient (P8A) with autosomal recessive Bethlem myopathy-1C (BTHLM1C; 620726) by Panades-de Oliveira et al. (2019), see 120250.0012. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 BETHLEM MYOPATHY 1C, AUTOSOMAL RECESSIVE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
COL6A3, ARG1597TER
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV004554350, RCV004595715
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the c.4789C-T transition in the COL6A3 gene, resulting in an arg1597-to-ter (R1597X) substitution, that was found in compound heterozygous state in 2 sibs (family 1) with autosomal recessive Bethlem myopathy-1C (BTHLM1C; 620726) by Villar-Quiles et al. (2021), see 120250.0012. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Baker, N. L., Morgelin, M., Pace, R. A., Peat, R. A., Adams, N. E., Gardner, R. J. M., Rowland, L. P., Miller, G., De Jonghe, P., Ceulemans, B., Hannibal, M. C., Edwards, M., Thompson, E. M., Jacobson, R., Quinlivan, R. C. M., Aftimos, S., Kornberg, A. J., North, K. N., Bateman, J. F., Lamande, S. R.
|
|
<strong>Molecular consequences of dominant Bethlem myopathy collagen VI mutations.</strong>
|
|
Ann. Neurol. 62: 390-405, 2007.
|
|
|
|
|
|
[PubMed: 17886299]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.21213]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Baker, N. L., Morgelin, M., Peat, R., Goemans, N., North, K. N., Bateman, J. F., Lamande, S. R.
|
|
<strong>Dominant collagen VI mutations are a common cause of Ullrich congenital muscular dystrophy.</strong>
|
|
Hum. Molec. Genet. 14: 279-293, 2005.
|
|
|
|
|
|
[PubMed: 15563506]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi025]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chu, M.-L., Zhang, R.-Z., Pan, T.-C., Stokes, D., Conway, D., Kuo, H.-J., Glanville, R., Mayer, U., Mann, K., Deutzmann, R., Timpl, R.
|
|
<strong>Mosaic structure of globular domains in the human type VI collagen alpha-3 chain: similarity to von Willebrand factor, fibronectin, actin, salivary proteins and apotinin type protease inhibitors.</strong>
|
|
EMBO J. 9: 385-393, 1990.
|
|
|
|
|
|
[PubMed: 1689238]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1990.tb08122.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Demir, E., Sabatelli, P., Allamand, V., Ferreiro, A., Moghadaszadeh, B., Makrelouf, M., Topaloglu, H., Echenne, B., Merlini, E., Guicheney, P.
|
|
<strong>Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy.</strong>
|
|
Am. J. Hum. Genet. 70: 1446-1458, 2002.
|
|
|
|
|
|
[PubMed: 11992252]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/340608]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hamosh, A.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 7/10/2024.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jun, A. S., Liu, S. H., Koo, E. H., Do, D. V., Stark, W. J., Gottsch, J. D.
|
|
<strong>Microarray analysis of gene expression in human donor corneas.</strong>
|
|
Arch. Ophthal. 119: 1629-1634, 2001.
|
|
|
|
|
|
[PubMed: 11709013]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archopht.119.11.1629]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Klewer, S. E., Krob, S. L., Kolker, S. J., Kitten, G. T.
|
|
<strong>Expression of type VI collagen in the developing mouse heart.</strong>
|
|
Dev. Dyn. 211: 248-255, 1998.
|
|
|
|
|
|
[PubMed: 9520112]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1097-0177(199803)211:3<248::AID-AJA6>3.0.CO;2-H]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lampe, A. K., Dunn, D. M., von Niederhausern, A. C., Hamil, C., Aoyagi, A., Laval, S. H., Marie, S. K., Chu, M.-L., Swoboda, K., Muntoni, F., Bonnemann, C. G., Flanigan, K. M., Bushby, K. M. D., Weiss, R. B.
|
|
<strong>Automated genomic sequence analysis of the three collagen VI genes: applications to Ullrich congenital muscular dystrophy and Bethlem myopathy.</strong>
|
|
J. Med. Genet. 42: 108-120, 2005.
|
|
|
|
|
|
[PubMed: 15689448]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2004.023754]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mohire, M. D., Tandan, R., Fries, T. J., Little, B. W., Pendlebury, W. W., Bradley, W. G.
|
|
<strong>Early-onset benign autosomal dominant limb-girdle myopathy with contractures (Bethlem myopathy).</strong>
|
|
Neurology 38: 573-580, 1988.
|
|
|
|
|
|
[PubMed: 3352914]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/wnl.38.4.573]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nadeau, A., Kinali, M., Main, M., Jimenez-Mallebrera, C., Aloysius, A., Clement, E., North, B., Manzur, A. Y., Robb, S. A., Mercuri, E., Muntoni, F.
|
|
<strong>Natural history of Ullrich congenital muscular dystrophy.</strong>
|
|
Neurology 73: 25-31, 2009.
|
|
|
|
|
|
[PubMed: 19564581]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0b013e3181aae851]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pan, T.-C., Zhang, R.-Z., Pericak-Vance, M. A., Tandan, R., Fries, T., Stajich, J. M., Viles, K., Vance, J. M., Chu, M.-L., Speer, M. C.
|
|
<strong>Missense mutation in a von Willebrand factor type A domain of the alpha-3(VI) collagen gene (COL6A3) in a family with Bethlem myopathy.</strong>
|
|
Hum. Molec. Genet. 7: 807-812, 1998.
|
|
|
|
|
|
[PubMed: 9536084]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/7.5.807]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Panades-de Oliveira, L., Rodriguez-Lopez, C., Cantero Montenegro, D., Marcos Toledano, M. D. M., Fernandez-Marmiesse, A., Esteban Perez, J., Hernandez Lain, A., Dominguez-Gonzalez, C.
|
|
<strong>Bethlem myopathy: a series of 16 patients and description of seven new associated mutations.</strong>
|
|
J. Neurol. 266: 934-941, 2019.
|
|
|
|
|
|
[PubMed: 30706156]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00415-019-09217-z]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Speer, M. C., Tandan, R., Rao, P. N., Fries, T., Stajich, J. M., Bolhuis, P. A., Jobsis, G. J., Vance, J. M., Viles, K. D., Sheffield, K., James, C., Kahler, S. G., Pettenati, M., Gilbert, J. R., Denton, P. H., Yamaoka, L. H., Pericak-Vance, M. A.
|
|
<strong>Evidence for locus heterogeneity in the Bethlem myopathy and linkage to 2q37.</strong>
|
|
Hum. Molec. Genet. 5: 1043-1046, 1996.
|
|
|
|
|
|
[PubMed: 8817344]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/5.7.1043]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stokes, D. G., Saitta, B., Timpl, R., Chu, M.-L.
|
|
<strong>Human alpha-3(VI) collagen gene: characterization of exons coding for the amino-terminal globular domain and alternative splicing in normal and tumor cells.</strong>
|
|
J. Biol. Chem. 266: 8626-8633, 1991.
|
|
|
|
|
|
[PubMed: 2022673]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Villar-Quiles, R. N., Donkervoort, S., de Becdelievre, A., Gartioux, C., Jobic, V., Foley, A. R., McCarty, R. M., Hu, Y., Menassa, R., Michel, L., Gousse, G., Lacour, A., and 20 others.
|
|
<strong>Clinical and molecular spectrum associated with COL6A3 c.7447A-G p.(Lys2483Glu) variant: elucidating its role in collagen VI-related myopathies.</strong>
|
|
J. Neuromusc. Dis. 8: 633-645, 2021.
|
|
|
|
|
|
[PubMed: 33749658]
|
|
|
|
|
|
[Full Text: https://doi.org/10.3233/JND-200577]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Weil, D., Mattei, M.-G., Passage, E., Van Cong, N., Pribula-Conway, D., Mann, K., Deutzmann, R., Timpl, R., Chu, M.-L.
|
|
<strong>Assignment of the three genes coding for the different chains of type VI collagen (COL6A1, COL6A2, COL6A3). (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 46: 713 only, 1987.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Weil, D., Mattei, M.-G., Passage, E., Van Cong, N., Pribula-Conway, D., Mann, K., Deutzmann, R., Timpl, R., Chu, M.-L.
|
|
<strong>Cloning and chromosomal localization of human genes encoding the three chains of type VI collagen.</strong>
|
|
Am. J. Hum. Genet. 42: 435-445, 1988.
|
|
|
|
|
|
[PubMed: 3348212]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zech, M., Lam, D. D., Francescatto, L., Schormair, B., Salminen, A. V., Jochim, A., Wieland, T., Lichtner, P., Peters, A., Gieger, C., Lochmuller, H., Strom, T. M., Haslinger, B., Katsanis, N., Winkelmann, J.
|
|
<strong>Recessive mutations in the alpha-3 (VI) collagen gene COL6A3 cause early-onset isolated dystonia.</strong>
|
|
Am. J. Hum. Genet. 96: 883-893, 2015.
|
|
|
|
|
|
[PubMed: 26004199]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2015.04.010]
|
|
|
|
|
|
</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 : 07/10/2024<br>Hamosh, A.: - updated : 07/10/2024<br>Cassandra L. Kniffin - updated : 6/4/2015<br>Cassandra L. Kniffin - updated : 12/15/2009<br>Cassandra L. Kniffin - updated : 5/23/2008<br>George E. Tiller - updated : 11/8/2007<br>Marla J. F. O'Neill - updated : 3/1/2005<br>Jane Kelly - updated : 12/6/2002<br>Victor A. McKusick - updated : 6/11/2002<br>Victor A. McKusick - updated : 5/22/1998<br>Paul Brennan - updated : 5/14/1998<br>Mark H. Paalman - updated : 8/15/1996
|
|
</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 : 2/9/1987
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 07/15/2024<br>carol : 07/15/2024<br>ckniffin : 07/10/2024<br>carol : 06/06/2024<br>ckniffin : 06/05/2024<br>carol : 02/29/2024<br>carol : 02/22/2024<br>carol : 02/21/2024<br>carol : 02/20/2024<br>carol : 07/20/2015<br>joanna : 6/16/2015<br>carol : 6/5/2015<br>mcolton : 6/5/2015<br>ckniffin : 6/4/2015<br>mcolton : 3/3/2015<br>carol : 12/23/2009<br>ckniffin : 12/15/2009<br>wwang : 7/8/2008<br>ckniffin : 7/2/2008<br>ckniffin : 5/23/2008<br>wwang : 11/30/2007<br>terry : 11/8/2007<br>wwang : 3/14/2005<br>wwang : 3/8/2005<br>terry : 3/1/2005<br>carol : 12/6/2002<br>alopez : 6/13/2002<br>terry : 6/11/2002<br>terry : 6/11/2002<br>dkim : 12/9/1998<br>terry : 6/3/1998<br>terry : 5/22/1998<br>carol : 5/14/1998<br>terry : 9/5/1996<br>terry : 9/3/1996<br>terry : 8/16/1996<br>mark : 8/15/1996<br>mark : 8/15/1996<br>carol : 10/7/1994<br>supermim : 3/16/1992<br>carol : 7/24/1991<br>carol : 7/12/1991<br>supermim : 3/20/1990<br>ddp : 10/26/1989
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div id="mimFooter">
|
|
|
|
|
|
<div class="container ">
|
|
<div class="row">
|
|
<br />
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="hidden-print mim-footer">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="visible-print-block mim-footer" style="position: relative;">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
<br />
|
|
Printed: March 5, 2025
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
|
|
<div class="modal-dialog" role="document">
|
|
<div class="modal-content">
|
|
<div class="modal-header">
|
|
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">×</span></button>
|
|
<h4 class="modal-title" id="mimDonationPopupModalTitle">
|
|
OMIM Donation:
|
|
</h4>
|
|
</div>
|
|
<div class="modal-body">
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Dear OMIM User,
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
To ensure long-term funding for the OMIM project, we have diversified
|
|
our revenue stream. We are determined to keep this website freely
|
|
accessible. Unfortunately, it is not free to produce. Expert curators
|
|
review the literature and organize it to facilitate your work. Over 90%
|
|
of the OMIM's operating expenses go to salary support for MD and PhD
|
|
science writers and biocurators. Please join your colleagues by making a
|
|
donation now and again in the future. Donations are an important
|
|
component of our efforts to ensure long-term funding to provide you the
|
|
information that you need at your fingertips.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Thank you in advance for your generous support, <br />
|
|
Ada Hamosh, MD, MPH <br />
|
|
Scientific Director, OMIM <br />
|
|
</p>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div class="modal-footer">
|
|
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
</body>
|
|
|
|
</html>
|
|
|
|
|