10661 lines
1 MiB
10661 lines
1 MiB
|
|
|
|
|
|
|
|
|
|
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
|
|
|
|
<head>
|
|
|
|
|
|
|
|
<!--
|
|
################################# CRAWLER WARNING #################################
|
|
|
|
- The terms of service and the robots.txt file disallows crawling of this site,
|
|
please see https://omim.org/help/agreement for more information.
|
|
|
|
- A number of data files are available for download at https://omim.org/downloads.
|
|
|
|
- We have an API which you can learn about at https://omim.org/help/api and register
|
|
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
|
|
|
|
- You should feel free to contact us at https://omim.org/contact to figure out the best
|
|
approach to getting the data you need for your work.
|
|
|
|
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
|
|
|
|
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
|
|
DISTRIBUTED CRAWLS OF THIS SITE.
|
|
|
|
################################# CRAWLER WARNING #################################
|
|
-->
|
|
|
|
|
|
|
|
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
|
|
<meta http-equiv="cache-control" content="no-cache" />
|
|
<meta http-equiv="pragma" content="no-cache" />
|
|
<meta name="robots" content="index, follow" />
|
|
|
|
|
|
<meta name="viewport" content="width=device-width, initial-scale=1" />
|
|
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
|
|
|
|
|
|
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
|
|
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
|
|
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
|
|
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
|
|
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
|
|
contain copious links to other genetics resources." />
|
|
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
|
|
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
|
|
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
|
|
<meta name="theme-color" content="#333333" />
|
|
<link rel="icon" href="/static/omim/favicon.png" />
|
|
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
|
|
<link rel="manifest" href="/static/omim/manifest.json" />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script id='mimBrowserCapability'>
|
|
function _0x5069(){const _0x4b1387=['91sZIeLc','mimBrowserCapability','15627zshTnf','710004yxXedd','34LxqNYj','match','disconnect','1755955rnzTod','observe','1206216ZRfBWB','575728fqgsYy','webdriver','documentElement','close','open','3086704utbakv','7984143PpiTpt'];_0x5069=function(){return _0x4b1387;};return _0x5069();}function _0xe429(_0x472ead,_0x43eb70){const _0x506916=_0x5069();return _0xe429=function(_0xe42949,_0x1aaefc){_0xe42949=_0xe42949-0x1a9;let _0xe6add8=_0x506916[_0xe42949];return _0xe6add8;},_0xe429(_0x472ead,_0x43eb70);}(function(_0x337daa,_0x401915){const _0x293f03=_0xe429,_0x5811dd=_0x337daa();while(!![]){try{const _0x3dc3a3=parseInt(_0x293f03(0x1b4))/0x1*(-parseInt(_0x293f03(0x1b6))/0x2)+parseInt(_0x293f03(0x1b5))/0x3+parseInt(_0x293f03(0x1b0))/0x4+-parseInt(_0x293f03(0x1b9))/0x5+parseInt(_0x293f03(0x1aa))/0x6+-parseInt(_0x293f03(0x1b2))/0x7*(parseInt(_0x293f03(0x1ab))/0x8)+parseInt(_0x293f03(0x1b1))/0x9;if(_0x3dc3a3===_0x401915)break;else _0x5811dd['push'](_0x5811dd['shift']());}catch(_0x4dd27b){_0x5811dd['push'](_0x5811dd['shift']());}}}(_0x5069,0x84d63),(function(){const _0x9e4c5f=_0xe429,_0x363a26=new MutationObserver(function(){const _0x458b09=_0xe429;if(document!==null){let _0x2f0621=![];navigator[_0x458b09(0x1ac)]!==![]&&(_0x2f0621=!![]);for(const _0x427dda in window){_0x427dda[_0x458b09(0x1b7)](/cdc_[a-z0-9]/ig)&&(_0x2f0621=!![]);}_0x2f0621===!![]?document[_0x458b09(0x1af)]()[_0x458b09(0x1ae)]():(_0x363a26[_0x458b09(0x1b8)](),document['getElementById'](_0x458b09(0x1b3))['remove']());}});_0x363a26[_0x9e4c5f(0x1a9)](document[_0x9e4c5f(0x1ad)],{'childList':!![]});}()));
|
|
</script>
|
|
|
|
|
|
|
|
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
|
|
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
|
|
|
|
<link rel="preconnect" href="https://www.googletagmanager.com" />
|
|
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
|
|
<script>
|
|
window.dataLayer = window.dataLayer || [];
|
|
function gtag(){window.dataLayer.push(arguments);}
|
|
gtag("js", new Date());
|
|
gtag("config", "G-HMPSQC23JJ");
|
|
</script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
|
|
|
|
|
|
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
|
|
|
|
|
|
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimBootstrapDeviceSize">
|
|
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
|
|
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
|
|
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
|
|
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
|
|
</div>
|
|
|
|
|
|
|
|
<title>
|
|
|
|
Entry
|
|
|
|
- *613160 - VON WILLEBRAND FACTOR; VWF
|
|
|
|
|
|
- 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=613160"><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 class="hidden-sm hidden-xs">
|
|
|
|
|
|
Display:
|
|
|
|
|
|
<label style="font-weight: normal"><input type="checkbox" id="mimToggleChangeBars" checked /> Change Bars </label>
|
|
|
|
|
|
</span>
|
|
|
|
|
|
</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">*613160</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#biochemicalFeatures">Biochemical Features</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/613160">Table View</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#seeAlso"><strong>See Also</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000110799;t=ENST00000261405" 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=7450" 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=613160" 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=ENSG00000110799;t=ENST00000261405" 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_000552,XM_047429501" 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_000552" 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=613160" 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://www.proteinatlas.org/search/VWF" 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/37940,37942,37947,340309,340314,340316,340356,340361,553810,1200090,1769552,18490128,119609220,119609221,119609222,119609223,119609224,158257676,194375357,194387242,194389732,311460884,317373549,373501907,442564354,550553674,1813372009,1839275809,2217290913,2462534198" 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/P04275" 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=7450" 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=ENSG00000110799;t=ENST00000261405" 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=VWF" 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=VWF" 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+7450" 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/VWF" 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:7450" 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/7450" 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=chr12&hgg_gene=ENST00000261405.10&hgg_start=5948877&hgg_end=6124670&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:12726" 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/vwf" 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=613160[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=613160[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://gnomad.broadinstitute.org/gene/ENSG00000110799" 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=VWF" 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=VWF" 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=VWF" 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="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=VWF&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/PA37337" 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:12726" 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:98941" 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/VWF#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:98941" 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/7450/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=001056,001057,001058,001339" 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=7450" 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://zfin.org/ZDB-GENE-070103-1" 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="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:7450" 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=VWF&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> 128106003, 128108002, 359711001, 359717002, 359732009<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> D68.01, D68.020, D68.021, D68.022, D68.023, D68.03<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>
|
|
613160
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
VON WILLEBRAND FACTOR; VWF
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
FACTOR VIII-VON WILLEBRAND FACTOR; F8VWF
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=VWF" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">VWF</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/12/45?start=-3&limit=10&highlight=45">12p13.31</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr12:5948877-6124670&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'})">12:5,948,877-6,124,670</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=193400,277480,613554" 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/12/45?start=-3&limit=10&highlight=45">
|
|
12p13.31
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
von Willebrand disease, type 1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/193400"> 193400 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
von Willebrand disease, type 3
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/277480"> 277480 </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">
|
|
von Willebrand disease, types 2A, 2B, 2M, and 2N
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/613554"> 613554 </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/613160" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/613160" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>The VWF gene encodes von Willebrand factor (VWF), a large multimeric glycoprotein that plays a central role in the blood coagulation system, serving both as a major mediator of platelet-vessel wall interaction and platelet adhesion, and as a carrier for coagulation factor VIII (F8; <a href="/entry/300841">300841</a>). Diminished or abnormal VWF activity results in von Willebrand disease (VWD; see <a href="/entry/193400">193400</a>), a common and complex hereditary bleeding disorder (<a href="#31" class="mim-tip-reference" title="Ginsburg, D., Handin, R. I., Bonthron, D. T., Donlon, T. A., Bruns, G. A. P., Latt, S. A., Orkin, S. H. <strong>Human von Willebrand factor (vWF): isolation of complementary DNA (cDNA) clones and chromosomal localization.</strong> Science 228: 1401-1406, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3874428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3874428</a>] [<a href="https://doi.org/10.1126/science.3874428" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3874428">Ginsburg et al., 1985</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3874428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The receptor for von Willebrand factor is a large complex comprising 4 proteins: glycoprotein Ib (GP1BA; <a href="/entry/606672">606672</a> and GP1BB; <a href="/entry/138720">138720</a>), platelet glycoprotein IX (GP9; 173515) and platelet glycoprotein V (GP5; 173511).</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="#31" class="mim-tip-reference" title="Ginsburg, D., Handin, R. I., Bonthron, D. T., Donlon, T. A., Bruns, G. A. P., Latt, S. A., Orkin, S. H. <strong>Human von Willebrand factor (vWF): isolation of complementary DNA (cDNA) clones and chromosomal localization.</strong> Science 228: 1401-1406, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3874428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3874428</a>] [<a href="https://doi.org/10.1126/science.3874428" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3874428">Ginsburg et al. (1985)</a> isolated overlapping cDNA clones corresponding to the human VWF gene. The 8.2-kb transcript accounted for approximately 0.3% of endothelial cell mRNA, but was undetectable in several other tissues examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3874428" 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="#85" class="mim-tip-reference" title="Sadler, J. E., Shelton-Inloes, B. B., Sorace, J. M., Harlan, J. M., Titani, K., Davie, E. W. <strong>Cloning and characterization of two cDNAs coding for human von Willebrand factor.</strong> Proc. Nat. Acad. Sci. 82: 6394-6398, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2864688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2864688</a>] [<a href="https://doi.org/10.1073/pnas.82.19.6394" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2864688">Sadler et al. (1985)</a> isolated cDNA clones from cultured human umbilical vein endothelial cells. Two inserts, which together coded for about 80% of the protein, were identified. One corresponded to residues 1 to 110 of the circulating mature protein and the second coded for 1,525 residues at the C terminus; there was about a 350-residue gap between the 2 clones. At least 3 separate polypeptide segments showed evidence of internal duplication, suggesting a complex evolutionary history. The full-length mature protein contains 2,050 amino acids (<a href="#94" class="mim-tip-reference" title="Titani, K., Kumar, S., Takio, K., Ericsson, L. H., Wade, R. D., Ashida, K., Walsh, K. A., Chopek, M. W., Sadler, J. E., Fujikawa, K. <strong>Amino acid sequence of human von Willebrand factor.</strong> Biochemistry 25: 3171-3184, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3524673/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3524673</a>] [<a href="https://doi.org/10.1021/bi00359a015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3524673">Titani et al., 1986</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2864688+3524673" 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="#6" class="mim-tip-reference" title="Bonthron, D., Orr, E. C., Mitsock, L. M., Ginsburg, D., Handin, R. I., Orkin, S. H. <strong>Nucleotide sequence of pre-pro-von Willebrand factor cDNA.</strong> Nucleic Acids Res. 14: 7125-7127, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3489923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3489923</a>] [<a href="https://doi.org/10.1093/nar/14.17.7125" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3489923">Bonthron et al. (1986)</a> presented the nucleotide sequence of pre-pro-von Willebrand factor cDNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3489923" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#52" class="mim-tip-reference" title="Lynch, D. C., Zimmerman, T. S., Collins, C. J., Morin, M. J., Ling, E. H., Livingston, D. M. <strong>Molecular cloning of mRNA for human von Willebrand factor. (Abstract)</strong> Clin. Res. 33: 548, 1985."None>Lynch et al. (1985)</a> also cloned the VWF gene, and <a href="#53" class="mim-tip-reference" title="Lynch, D. C., Zimmerman, T. S., Ruggeri, Z. M. <strong>Von Willebrand factor, now cloned. (Annotation).</strong> Brit. J. Haemat. 64: 15-20, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3489483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3489483</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1986.tb07569.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3489483">Lynch et al. (1986)</a> stated that 4 separate groups had reported isolation of VWF-specific clones from human endothelial cell cDNA libraries. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3489483" 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>VWF is synthesized in endothelial cells and megakaryocytes as a 2,813-residue pre-protein. It dimerizes, undergoes extensive posttranslational modification, and is packaged as a mature protein into endothelial cell Weibel-Palade bodies and platelet alpha granules. Endothelial cells secrete VWF constitutively, whereas platelets release VWF when stimulated. Circulating VWF multimers are composed of up to 40 subunits and range in size from 500 to 10,000 kD (review by <a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve, 2010</a>). VWF is synthesized in megakaryocytes and endothelial cells with a 22-amino acid signal peptide, 741-amino acid propeptide and 2,050-amino acid mature VWF (review by <a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve, 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" 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="#55" class="mim-tip-reference" title="Mancuso, D. J., Tuley, E. A., Westfield, L. A., Worrall, N. K., Shelton-Inloes, B. B., Sorace, J. M., Alevy, Y. G., Sadler, J. E. <strong>Structure of the gene for human von Willebrand factor.</strong> J. Biol. Chem. 264: 19514-19527, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2584182/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2584182</a>]" pmid="2584182">Mancuso et al. (1989)</a> concluded that the VWF gene is approximately 178 kb long and contains 52 exons. The exons vary from 40 to 1379 bp, and the introns from 97 bp to approximately 19.9 kb. The signal peptide and propeptide (von Willebrand antigen II) are encoded by 17 exons in approximately 80 kb of DNA, while the mature subunit of von Willebrand factor and the 3-prime noncoding region are encoded by 35 exons in the remainder of the gene. A number of repetitive sequences were identified, including 14 Alu repeats and a polymorphic TCTA simple repeat of about 670 bp in intron 40. Regions of the gene that encode homologous domains have similar structures, supporting a model for their origin by gene segment duplication. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2584182" 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>From a study of a series of overlapping cosmid genomic clones of VWF, <a href="#14" class="mim-tip-reference" title="Collins, C. J., Underdahl, J. P., Levene, R. B., Ravera, C. P., Morin, M. J., Dombalagian, M. J., Ricca, G., Livingston, D. M., Lynch, D. C. <strong>Molecular cloning of the human gene for von Willebrand factor and identification of the transcription initiation site.</strong> Proc. Nat. Acad. Sci. 84: 4393-4397, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3496594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3496594</a>] [<a href="https://doi.org/10.1073/pnas.84.13.4393" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3496594">Collins et al. (1987)</a> identified the transcription initiation site, a portion of the promoter region, and the translation termination codon. Their evidence supported the existence of a single VWF gene in the haploid genome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3496594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#97" class="mim-tip-reference" title="Verweij, C. L., de Vries, C. J. M., Distel, B., van Zonneveld, A.-J., Geurts van Kessel, A., van Mourik, J. A., Pannekoek, H. <strong>Construction of cDNA coding for human von Willebrand factor using antibody probes for colony-screening and mapping of the chromosomal gene.</strong> Nucleic Acids Res. 13: 4699-4717, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3875078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3875078</a>] [<a href="https://doi.org/10.1093/nar/13.13.4699" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3875078">Verweij et al. (1985)</a> cloned the gene for VWF and assigned it to chromosome 12 using cDNA probes with panels of human-rodent hybrid cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3875078" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By somatic cell hybridization and in situ hybridization using a cDNA clone of the gene, <a href="#31" class="mim-tip-reference" title="Ginsburg, D., Handin, R. I., Bonthron, D. T., Donlon, T. A., Bruns, G. A. P., Latt, S. A., Orkin, S. H. <strong>Human von Willebrand factor (vWF): isolation of complementary DNA (cDNA) clones and chromosomal localization.</strong> Science 228: 1401-1406, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3874428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3874428</a>] [<a href="https://doi.org/10.1126/science.3874428" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3874428">Ginsburg et al. (1985)</a> assigned the VWF gene to 12pter-p12. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3874428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#90" class="mim-tip-reference" title="Shelton-Inloes, B. B., Chehab, F. F., Mannucci, P. M., Federici, A. B., Sadler, J. E. <strong>Gene deletions correlate with the development of alloantibodies in von Willebrand disease.</strong> J. Clin. Invest. 79: 1459-1465, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3033024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3033024</a>] [<a href="https://doi.org/10.1172/JCI112974" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3033024">Shelton-Inloes et al. (1987)</a> confirmed the localization of the gene to chromosome 12 and identified a homologous sequence on chromosome 22. The VWF gene is the most distally mapped gene on 12p13.3 (<a href="#67" class="mim-tip-reference" title="NIH/CEPH Collaborative Mapping Group. <strong>A comprehensive genetic linkage map of the human genome.</strong> Science 258: 67-86, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1439770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1439770</a>]" pmid="1439770">NIH/CEPH Collaborative Mapping Group, 1992</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1439770+3033024" 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="#3" class="mim-tip-reference" title="Barrow, L. L., Simin, K., Mohlke, K., Nichols, W. C., Ginsburg, D., Meisler, M. H. <strong>Conserved linkage of neurotrophin-3 and von Willebrand factor on mouse chromosome 6.</strong> Mammalian Genome 4: 343-345, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8318738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8318738</a>] [<a href="https://doi.org/10.1007/BF00357095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8318738">Barrow et al. (1993)</a> showed that the loci for neurotrophin-3 (NTF3; <a href="/entry/162660">162660</a>) and von Willebrand factor map to 12p13 in the human and are closely linked on mouse chromosome 6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8318738" 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>Pseudogene</em></strong></p><p>
|
|
<a href="#54" class="mim-tip-reference" title="Mancuso, D. J., Tuley, E. A., Westfield, L. A., Lester-Mancuso, T. L., Le Beau, M. M., Sorace, J. M., Sadler, J. E. <strong>Human von Willebrand factor gene and pseudogene: structural analysis and differentiation by polymerase chain reaction.</strong> Biochemistry 30: 253-269, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1988024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1988024</a>] [<a href="https://doi.org/10.1021/bi00215a036" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1988024">Mancuso et al. (1991)</a> reported that the partially unprocessed pseudogene on chromosome 22q11-q13 is 21 to 29 kb long and corresponds to exons 23 to 34 of the VWF gene. They found splice site and nonsense mutations, suggesting that the pseudogene cannot yield functional transcripts. By in situ hybridization experiments on metaphase spreads from a Philadelphia-chromosome-positive chronic myelogenous leukemia (<a href="/entry/151410">151410</a>) patient, <a href="#69" class="mim-tip-reference" title="Patracchini, P., Marchetti, G., Aiello, V., Croci, G., Calzolari, E., Bernardi, F. <strong>Characterization and mapping of the 5-prime portion of von Willebrand factor pseudogene.</strong> Hum. Genet. 90: 297-298, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1487245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1487245</a>] [<a href="https://doi.org/10.1007/BF00220083" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1487245">Patracchini et al. (1992)</a> found that the pseudogene is located centromeric to the breakpoint cluster region. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1487245+1988024" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneFunction" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneFunctionFold" id="mimGeneFunctionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneFunctionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneFunctionFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#81" class="mim-tip-reference" title="Ruggeri, Z. M. <strong>Von Willebrand factor.</strong> J. Clin. Invest. 99: 559-564, 1997. Note: Erratum: J. Clin. Invest. 100: 237 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9045854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9045854</a>] [<a href="https://doi.org/10.1172/JCI119195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9045854">Ruggeri (1997)</a> reviewed VWF within a series on cell adhesion in vascular biology and took the opportunity to review the understanding of platelet function in hemostasis and thrombosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9045854" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#91" class="mim-tip-reference" title="Sporn, L. A., Marder, V. J., Wagner, D. D. <strong>Von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively.</strong> Blood 69: 1531-1534, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3105624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3105624</a>]" pmid="3105624">Sporn et al. (1987)</a> found that the VWF released from endothelial cell Weibel-Palade bodies bound particularly avidly to the extracellular matrix. <a href="#100" class="mim-tip-reference" title="Wagner, D. D., Saffaripour, S., Bonfanti, R., Sadler, J. E., Cramer, E. M., Chapman, B., Mayadas, T. N. <strong>Induction of specific storage organelles by von Willebrand factor propolypeptide.</strong> Cell 64: 403-413, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1988154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1988154</a>] [<a href="https://doi.org/10.1016/0092-8674(91)90648-i" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1988154">Wagner et al. (1991)</a> showed that the VWF propolypeptide is necessary for the formation of the Weibel-Palade storage granules. Following secretagogue stimulation, Weibel-Palade bodies undergo exocytosis and release long VWF filaments, averaging 100 micrometers, that capture platelets along their length. Subsequent activation and aggregation of platelets cause the formation of a hemostatic plug (<a href="#62" class="mim-tip-reference" title="Michaux, G., Abbitt, K. B., Collinson, L. M., Haberichter, S. L., Norman, K. E., Cutler, D. F. <strong>The physiological function of von Willebrand's factor depends on its tubular storage in endothelial Weibel-Palade bodies.</strong> Dev. Cell 10: 223-232, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16459301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16459301</a>] [<a href="https://doi.org/10.1016/j.devcel.2005.12.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16459301">Michaux et al., 2006</a>). <a href="#62" class="mim-tip-reference" title="Michaux, G., Abbitt, K. B., Collinson, L. M., Haberichter, S. L., Norman, K. E., Cutler, D. F. <strong>The physiological function of von Willebrand's factor depends on its tubular storage in endothelial Weibel-Palade bodies.</strong> Dev. Cell 10: 223-232, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16459301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16459301</a>] [<a href="https://doi.org/10.1016/j.devcel.2005.12.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16459301">Michaux et al. (2006)</a> determined that the propeptide of VWF, which is released into the bloodstream at exocytosis, was involved in a pH-dependent interaction with the first 3 domains of mature VWF protein and this interaction was required for compact storage of VWF filaments. They showed that multimerization and tubular storage were a prerequisite for rapid unfurling of long VWF filaments in stimulated human umbilical vein endothelial cells in culture and in laser-injured cremaster venules in mice. If tubules were disassembled prior to exocytosis, short or tangled filaments were released and platelet recruitment was reduced. <a href="#62" class="mim-tip-reference" title="Michaux, G., Abbitt, K. B., Collinson, L. M., Haberichter, S. L., Norman, K. E., Cutler, D. F. <strong>The physiological function of von Willebrand's factor depends on its tubular storage in endothelial Weibel-Palade bodies.</strong> Dev. Cell 10: 223-232, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16459301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16459301</a>] [<a href="https://doi.org/10.1016/j.devcel.2005.12.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16459301">Michaux et al. (2006)</a> concluded that compaction of VWF into tubules determines the rod-like shape of Weibel-Palade bodies and is critical to the protein's hemostatic function. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3105624+1988154+16459301" 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>ADAMTS13 (<a href="/entry/604134">604134</a>) specifically cleaves a peptidyl bond between tyr1605 and met1606 in the A2 domain of VWF and thus acts to regulate VWF size. <a href="#48" class="mim-tip-reference" title="Kokame, K., Matsumoto, M., Fujimura, Y., Miyata, T. <strong>VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS-13.</strong> Blood 103: 607-612, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14512308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14512308</a>] [<a href="https://doi.org/10.1182/blood-2003-08-2861" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14512308">Kokame et al. (2004)</a> identified a 73-amino acid peptide, which they designated VWF73, as the minimal VWF substrate cleavable by ADAMTS13. VWF73 contains asp1596 to arg1668 of VWF. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14512308" 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="#104" class="mim-tip-reference" title="Wu, J.-J., Fujikawa, K., McMullen, B. A., Chung, D. W. <strong>Characterization of a core binding site for ADAMTS-13 in the A2 domain of von Willebrand factor.</strong> Proc. Nat. Acad. Sci. 103: 18470-18474, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17121983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17121983</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17121983[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0609190103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17121983">Wu et al. (2006)</a> cleaved VWF73 into shorter peptides and found that a 24-amino acid peptide encompassing pro1645 to lys1668 was the shortest peptide that could bind ADAMTS13 and competitively inhibit its cleavage of a VWF-derived substrate. This peptide and longer peptides containing this core sequence also inhibited cleavage of multimeric VWF by ADAMTS13. These results suggested the presence of a complementary extended binding site, or exosite, on ADAMTS13. Asp1653-to-ala and asp1663-to-ala mutations in the VWF-derived substrate significantly reduced the rate of cleavage of the substrate peptide by ADAMTS13, whereas a glu1655-to-ala mutation significantly enhanced the rate of cleavage. <a href="#104" class="mim-tip-reference" title="Wu, J.-J., Fujikawa, K., McMullen, B. A., Chung, D. W. <strong>Characterization of a core binding site for ADAMTS-13 in the A2 domain of von Willebrand factor.</strong> Proc. Nat. Acad. Sci. 103: 18470-18474, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17121983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17121983</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17121983[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0609190103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17121983">Wu et al. (2006)</a> concluded that ionic interactions between the exosite on ADAMTS13 and a region of VWF spanning pro1645 to lys1668 play a significant role in substrate recognition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17121983" 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="Cao, W., Krishnaswamy, S., Camire, R. M., Lenting, P. J., Zheng, X. L. <strong>Factor VIII accelerates proteolytic cleavage of von Willebrand factor by ADAMTS13.</strong> Proc. Nat. Acad. Sci. 105: 7416-7421, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18492805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18492805</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18492805[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0801735105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18492805">Cao et al. (2008)</a> showed that, under shear stress and at physiologic pH and ionic strength, coagulation factor VIII (F8; <a href="/entry/300841">300841</a>) accelerated, by a factor of about 10, the rate of ADAMTS13-mediated cleavage of the tyr1605/met1606 bond in VWF. Multimer analysis revealed that factor VIII preferentially accelerated the cleavage of high molecular weight (HMW) multimers. The ability of factor VIII to enhance VWF cleavage by ADAMTS13 was rapidly lost after pretreatment of factor VIII with thrombin (F2; <a href="/entry/176930">176930</a>). <a href="#10" class="mim-tip-reference" title="Cao, W., Krishnaswamy, S., Camire, R. M., Lenting, P. J., Zheng, X. L. <strong>Factor VIII accelerates proteolytic cleavage of von Willebrand factor by ADAMTS13.</strong> Proc. Nat. Acad. Sci. 105: 7416-7421, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18492805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18492805</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18492805[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0801735105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18492805">Cao et al. (2008)</a> concluded that factor VIII regulates proteolytic processing of VWF by ADAMTS13 under shear stress, which depends on the high-affinity interaction between factor VIII and VWF. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18492805" 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 recombinant variants of ADAMTS13 and VWF for kinetic analysis, <a href="#27" class="mim-tip-reference" title="Gao, W., Anderson, P. J., Sadler, J. E. <strong>Extensive contacts between ADAMTS13 exosites and von Willebrand factor domain A2 contribute to substrate specificity.</strong> Blood 112: 1713-1719, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18492952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18492952</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18492952[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/10.1182/blood-2008-04-148759" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18492952">Gao et al. (2008)</a> determined that segments between gln1624 and arg1668 in the VWF A2 domain interacted with the first thrombospondin-1 (see <a href="/entry/188060">188060</a>) domain, the cys-rich domain, and the spacer domain of ADAMTS13. The individual interactions were relatively weak, but together they increased the rate of substrate cleavage. Internal deletion of gln1624 to arg1641 in the VWF A2 domain did not affect the cleavage rate, but short deletions on either side of the tyr1605-met1606 cleavage site abolished cleavage. Adding residues N-terminal to glu1554 in VWF reduced the rate of VWF cleavage by ADAMTS13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18492952" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="biochemicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimBiochemicalFeaturesFold" id="mimBiochemicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimBiochemicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimBiochemicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
<a href="#45" class="mim-tip-reference" title="Huizinga, E. G., Tsuji, S., Romijn, R. A. P., Schiphorst, M. E., de Groot, P. G., Sixma, J. J., Gros, P. <strong>Structures of glycoprotein Ib-alpha and its complex with von Willebrand factor A1 domain.</strong> Science 297: 1176-1179, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12183630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12183630</a>] [<a href="https://doi.org/10.1126/science.107355" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12183630">Huizinga et al. (2002)</a> presented the crystal structure of the platelet receptor glycoprotein 1B-alpha (GP1BA; <a href="/entry/606672">606672</a>) amino-terminal domain and its complex with the VWF domain A1. In the complex, GP1BA wraps around one side of A1, providing 2 contact areas bridged by an area of solvated charge interaction. The structures explain the effects of gain-of-function mutations related to bleeding disorders and provide a model for shear-induced activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12183630" 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="#110" class="mim-tip-reference" title="Zhou, M., Dong, X., Baldauf, C., Chen, H., Zhou, Y., Springer, T. A., Luo, X., Zhong, C., Grater, F., Ding, J. <strong>A novel calcium-binding site of von Willebrand factor A2 domain regulates its cleavage by ADAMTS13.</strong> Blood 117: 4623-4631, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21385852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21385852</a>] [<a href="https://doi.org/10.1182/blood-2010-11-321596" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21385852">Zhou et al. (2011)</a> determined the crystal structure of an engineered VWF A2 domain. The structure contained a Ca(2+)-binding site in the region (residues 1591 to 1602) connecting alpha-3 to beta-4. Mutation of asp1596 or asn1602 impaired the ability of the A2 domain to bind Ca(2+). Ca(2+) binding stabilized the A2 domain and impeded unfolding of the A2 domain, thereby protecting it from cleavage by ADAMTS13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21385852" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#84" class="mim-tip-reference" title="Sadler, J. E., Ginsburg, D. <strong>A database of polymorphisms in the von Willebrand factor gene and pseudogene.</strong> Thromb. Haemost. 69: 185-191, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8456432/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8456432</a>]" pmid="8456432">Sadler and Ginsburg (1993)</a> reported on a database of polymorphisms in the VWF gene and pseudogene; <a href="#33" class="mim-tip-reference" title="Ginsburg, D., Sadler, J. E. <strong>Von Willebrand disease: a database of point mutations, insertions, and deletions.</strong> Thromb. Haemost. 69: 177-184, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8456431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8456431</a>]" pmid="8456431">Ginsburg and Sadler (1993)</a> reported on a database of point mutations, insertions, and deletions. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8456432+8456431" 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>Von Willebrand Disease Type 1</em></strong></p><p>
|
|
<a href="#23" class="mim-tip-reference" title="Eikenboom, J. C. J., Matsushita, T., Reitsma, P. H., Tuley, E. A., Castaman, G., Briet, E., Sadler, J. E. <strong>Dominant type 1 von Willebrand disease caused by mutated cysteine residues in the D3 domain of von Willebrand factor.</strong> Blood 88: 2433-2441, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8839833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8839833</a>]" pmid="8839833">Eikenboom et al. (1996)</a> described a family in the Netherlands in which 3 affected members with type 1 von Willebrand disease (<a href="/entry/193400">193400</a>) and VWF levels 10 to 15% of normal were heterozygous for a mutation in the VWF gene (C1149R; <a href="#0028">613160.0028</a>) The mutation resulted in a decrease in the secretion of coexpressed normal VWF, and the mutation was proposed to cause intracellular retention of pro-VWF heterodimers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8839833" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 7 Italian families and in 1 German patient with von Willebrand disease 'Vicenza,' <a href="#87" class="mim-tip-reference" title="Schneppenheim, R., Federici, A. B., Budde, U., Castaman, G., Drewke, E., Krey, S., Mannucci, P. M., Riesen, G., Rodeghiero, F., Zieger, B., Zimmermann, R. <strong>Von Willebrand disease type 2M 'Vicenza' in Italian and German patients: identification of the first candidate mutation (G3864A; R1205H) in 8 families.</strong> Thromb. Haemost. 83: 136-140, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10669167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10669167</a>]" pmid="10669167">Schneppenheim et al. (2000)</a> identified a heterozygous R1205H mutation in the VWF gene (<a href="#0027">613160.0027</a>). Haplotype identity, with minor deviations in 1 Italian family, suggested a common but not very recent genetic origin of R1205H. The phenotype was characterized by these groups as showing autosomal dominant inheritance and low levels of VWF antigen in the presence of high molecular weight and ultra high molecular weight multimers, so-called 'supranormal' multimers, similar to those seen in normal plasma after infusion of desmopressin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10669167" 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>Von Willebrand Disease Type 2</em></strong></p><p>
|
|
In a patient with type 2 von Willebrand disease (<a href="/entry/613554">613554</a>), <a href="#4" class="mim-tip-reference" title="Bernardi, F., Marchetti, G., Guerra, S., Casonato, A., Gemmati, D., Patracchini, P., Ballerini, G., Conconi, F. <strong>A de novo and heterozygous gene deletion causing a variant of von Willebrand disease.</strong> Blood 75: 677-683, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1967540/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1967540</a>]" pmid="1967540">Bernardi et al. (1990)</a> identified a heterozygous de novo deletion of a portion of the VWF gene containing at least codons 1147 through 1854. The VWF antigen (VWF:Ag) levels were one-fourth of normal, and ristocetin cofactor (VWF:RCo) activity was severely impaired. VWF morphology showed a reduction of high molecular weight multimers in plasma and platelets, consistent with type 2A VWD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1967540" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#46" class="mim-tip-reference" title="Iannuzzi, M. C., Hidaka, N., Boehnke, M., Bruck, M. E., Hanna, W. T., Collins, F. S., Ginsburg, D. <strong>Analysis of the relationship of von Willebrand disease (vWD) and hereditary hemorrhagic telangiectasia and identification of a potential type IIA vWD mutation (ile865-to-thr).</strong> Am. J. Hum. Genet. 48: 757-763, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1673047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1673047</a>]" pmid="1673047">Iannuzzi et al. (1991)</a> identified a heterozygous mutation in the VWF gene (<a href="#0001">613160.0001</a>) in a patient with von Willebrand disease type 2A, which is characterized by a qualitative defect in VWF, resulting in the absence of large and intermediate VWF multimers, which may be caused by increased VWF proteolysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1673047" 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 families with VWD, 1 with type 2B and another with type 1, <a href="#24" class="mim-tip-reference" title="Eikenboom, J. C. J., Vink, T., Briet, E., Sixma, J. J., Reitsma, P. H. <strong>Multiple substitutions in the von Willebrand factor gene that mimic the pseudogene sequence.</strong> Proc. Nat. Acad. Sci. 91: 2221-2224, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8134377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8134377</a>] [<a href="https://doi.org/10.1073/pnas.91.6.2221" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8134377">Eikenboom et al. (1994)</a> identified multiple consecutive nucleotide changes in the 5-prime end of exon 28 that resulted in sequences identical to the VWF pseudogene, although they were demonstrated to be in the active gene. <a href="#24" class="mim-tip-reference" title="Eikenboom, J. C. J., Vink, T., Briet, E., Sixma, J. J., Reitsma, P. H. <strong>Multiple substitutions in the von Willebrand factor gene that mimic the pseudogene sequence.</strong> Proc. Nat. Acad. Sci. 91: 2221-2224, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8134377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8134377</a>] [<a href="https://doi.org/10.1073/pnas.91.6.2221" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8134377">Eikenboom et al. (1994)</a> hypothesized that each of these multiple substitutions arose from a recombination event between the gene and pseudogene, rather than from single mutation events. The findings thus represented interchromosomal gene conversion involving chromosomes 12 and 22. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8134377" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 2 unrelated families with VWD type 2CB (see <a href="/entry/613554">613554</a>), <a href="#76" class="mim-tip-reference" title="Riddell, A. F., Gomez, K., Millar, C. M., Mellars, G., Gill, S., Brown, S. A., Sutherland, M., Laffan, M. A., McKinnon, T. A. <strong>Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor.</strong> Blood 114: 3489-3496, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687512</a>] [<a href="https://doi.org/10.1182/blood-2008-10-184317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19687512">Riddell et al. (2009)</a> identified 2 different heterozygous mutations in the collagen-binding A3 domain of the VWF gene (W1745C; <a href="#0040">613160.0040</a> and S1783A; <a href="#0042">613160.0042</a>, respectively). The patients had clinically significant bleeding episodes. Laboratory studies showed normal values of VWF:RCo to VWF:Ag (RCo:Ag), normal VWF multimer analysis, and normal ristocetin-induced platelet aggregation, but markedly reduced ratios of VWF collagen-binding activity to VWF antigen (CB:Ag) against type III collagen and type I collagen. Treatment with DDAVP resulted in a good functional response with a rise in VWF:CB resulting from an overall increase in the amount of circulating VWF, even though the qualitative defect in collagen binding remained. These findings and in vitro expression studies indicated that these mutant proteins caused a specific defect in collagen binding, which <a href="#76" class="mim-tip-reference" title="Riddell, A. F., Gomez, K., Millar, C. M., Mellars, G., Gill, S., Brown, S. A., Sutherland, M., Laffan, M. A., McKinnon, T. A. <strong>Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor.</strong> Blood 114: 3489-3496, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687512</a>] [<a href="https://doi.org/10.1182/blood-2008-10-184317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19687512">Riddell et al. (2009)</a> suggested represented a novel classification subtype termed 'VWF 2CB.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19687512" 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 decreased VWF:RCo/VWF:Ag ratio implies a VWD type 2M defect that is characterized by decreased VWF-platelet interactions in the presence of normal multimer structure. Based on laboratory findings, <a href="#26" class="mim-tip-reference" title="Flood, V. H., Gill, J. C., Morateck, P. A., Christopherson, P. A., Friedman, K. D., Haberichter, S. L., Branchford, B. R., Hoffmann, R. G., Abshire, T. C., Di Paola, J. A., Hoots, W. K, Leissinger, C., Lusher, J. M., Ragni, M. V., Shapiro, A. D., Montgomery, R. R. <strong>:Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor.</strong> Blood 116: 280-286, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20231421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20231421</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20231421[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/10.1182/blood-2009-10-249102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20231421">Flood et al. (2010)</a> observed an overrepresentation of VWD type 2M in African American individuals (80%) compared to Caucasians (30%), among all those categorized as having VWD type 2. In addition, most of the African American individuals had minimal bleeding symptoms despite a significantly reduced VWF:RCo/VWF:Ag ratio. Genetic analysis of 59 African American and 113 Caucasian controls identified a nonsynonymous SNP (asp1472-to-his; D1472H; <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1800383;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs1800383</a>) in exon 28 in the A1 domain of the VWF gene that could fully explain the lower VWF:RCo/VWF:Ag ratios in African Americans (0.81) compared to Caucasians (0.94). Whereas 63% of the African Americans were positive for D1472H, only 17% of Caucasians had this SNP. Further analysis showed that the VWF 1472H allele fully accounted for the variation in VWF:RCo/VWF:Ag independent of race. In vitro studies showed that the D1472H substitution had no effect on VWF binding to platelet GP1BA in assays that did not use ristocetin, and did not alter VWF binding to collagen. Therefore, the VWF D1472H polymorphism causes substantial variation in VWF:RCo without altering the hemostatic function of VWF in vivo. <a href="#26" class="mim-tip-reference" title="Flood, V. H., Gill, J. C., Morateck, P. A., Christopherson, P. A., Friedman, K. D., Haberichter, S. L., Branchford, B. R., Hoffmann, R. G., Abshire, T. C., Di Paola, J. A., Hoots, W. K, Leissinger, C., Lusher, J. M., Ragni, M. V., Shapiro, A. D., Montgomery, R. R. <strong>:Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor.</strong> Blood 116: 280-286, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20231421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20231421</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20231421[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/10.1182/blood-2009-10-249102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20231421">Flood et al. (2010)</a> concluded that polymorphisms in this region may affect the measurement of VWF activity by the ristocetin assay and may not reflect a functional defect or true hemorrhagic risk. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20231421" 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="#88" class="mim-tip-reference" title="Schneppenheim, R., Michiels, J. J., Obser, T., Oyen, F., Pieconka, A., Schneppenheim, S., Will, K., Zieger, B., Budde, U. <strong>A cluster of mutations in the D3 domain of von Willebrand factor correlates with a distinct subgroup of von Willebrand disease: type 2A/IIE.</strong> Blood 115: 4894-4901, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20351307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20351307</a>] [<a href="https://doi.org/10.1182/blood-2009-07-226324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20351307">Schneppenheim et al. (2010)</a> reported a high frequency (29%) of VWD type 2A subtype IIE among patients with type 2A studied in their laboratory. Subtype IIE is associated with a reduction of high molecular weight (HMW) VWF multimers and a lack of outer proteolytic bands on gel electrophoresis, indicating reduced proteolysis. Genetic analysis of 38 such index cases identified 22 different mutations in the VWF gene, most of them affecting cysteine residues clustered in the D3 domain. The most common mutation was Y1146C (<a href="#0039">613160.0039</a>), which was found in 12 (32%) probands. In vitro expression studies indicated that the Y1146C-mutant protein caused a severe reduction in or lack of HMW monomers and decreased secreted VWF antigen levels. However, clinical symptoms were heterogeneous among carriers, ranging from mild to severe bleeding. <a href="#88" class="mim-tip-reference" title="Schneppenheim, R., Michiels, J. J., Obser, T., Oyen, F., Pieconka, A., Schneppenheim, S., Will, K., Zieger, B., Budde, U. <strong>A cluster of mutations in the D3 domain of von Willebrand factor correlates with a distinct subgroup of von Willebrand disease: type 2A/IIE.</strong> Blood 115: 4894-4901, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20351307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20351307</a>] [<a href="https://doi.org/10.1182/blood-2009-07-226324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20351307">Schneppenheim et al. (2010)</a> suggested that several mechanisms likely act in concert to produce subtype IIE, including decreased secretion of VWF, the change of a cysteine residue which may impact multimerization, and decreased half-life of the mutant protein. Altered ADAMTS13-mediated proteolysis did not appear to be a major primary factor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20351307" 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>Von Willebrand Disease Type 3</em></strong></p><p>
|
|
In a patient with severe type 3 von Willebrand disease (<a href="/entry/277480">277480</a>), <a href="#70" class="mim-tip-reference" title="Peake, I. R., Liddell, M. B., Moodie, P., Standen, G., Mancuso, D. J., Tuley, E. A., Westfield, L. A., Sorace, J. M., Sadler, J. E., Verweij, C. L., Bloom, A. L. <strong>Severe type III von Willebrand's disease caused by deletion of exon 42 of the von Willebrand factor gene: family studies that identify carriers of the condition and a compound heterozygous individual.</strong> Blood 75: 654-661, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2297569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2297569</a>]" pmid="2297569">Peake et al. (1990)</a> found a homozygous 2.3-kb deletion in the VWF gene which included exon 42; a novel 182-bp insert was found between the breakpoints. The patient had an alloantibody inhibitor to VWF. The insert was detected by PCR amplification both in the patient's DNA and in his carrier relatives. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2297569" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In patients with VWD type 3, Zhang et al. (<a href="#108" class="mim-tip-reference" title="Zhang, Z. P., Falk, G., Blomback, M., Egberg, N., Anvret, M. <strong>Identification of a new nonsense mutation in the von Willebrand factor gene in patients with von Willebrand disease type III.</strong> Hum. Molec. Genet. 1: 61-62, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301136</a>] [<a href="https://doi.org/10.1093/hmg/1.1.61" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301136">1992</a>, <a href="#107" class="mim-tip-reference" " title="Zhang, Z. P., Falk, G., Blomback, M., Egberg, N., Anvret, M. <strong>A single cytosine deletion in exon 18 of the von Willebrand factor gene is the most common mutation in Swedish vWD type III patients.</strong> Hum. Molec. Genet. 1: 767-768, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1302613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1302613</a>] [<a href="https://doi.org/10.1093/hmg/1.9.767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1302613">1992</a>, <a href="#109" class="mim-tip-reference" title="Zhang, Z. P., Lindstedt, M., Falk, G., Blomback, M., Egberg, N., Anvret, M. <strong>Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I.</strong> Am. J. Hum. Genet. 51: 850-858, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1415226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1415226</a>]" pmid="1415226">1992</a>) identified homozygous or compound heterozygous mutations in the VWF gene (see, e.g., <a href="#0015">613160.0015</a>-<a href="#0017">613160.0017</a>). Some heterozygous family members had a less severe phenotype, consistent with VWD type 1. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1302613+1415226+1301136" 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="Denis, C., Methia, N., Frenette, P. S., Rayburn, H., Ullman-Cullere, M., Hynes, R. O., Wagner, D. D. <strong>A mouse model of severe von Willebrand disease: defects in hemostasis and thrombosis.</strong> Proc. Nat. Acad. Sci. 95: 9524-9529, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9689113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9689113</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9689113[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.95.16.9524" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9689113">Denis et al. (1998)</a> generated a mouse model for von Willebrand disease by using gene targeting. VWF-deficient mice appeared normal at birth; they were viable and fertile. Neither von Willebrand factor nor VWF-propolypeptide (von Willebrand antigen II) was detectable in plasma, platelets, or endothelial cells of the homozygous mutant mice. The mutant mice exhibited defects in hemostasis with a highly prolonged bleeding time and spontaneous bleeding events in approximately 10% of neonates. As in the human disease, the factor VIII level in these mice was reduced strongly as a result of the lack of protection provided by von Willebrand factor. Defective thrombosis in mutant mice was also evident in an in vivo model of vascular injury. In this model, the exteriorized mesentery was superfused with ferric chloride and the accumulation of fluorescently labeled platelets was observed by intravascular microscopy. <a href="#18" class="mim-tip-reference" title="Denis, C., Methia, N., Frenette, P. S., Rayburn, H., Ullman-Cullere, M., Hynes, R. O., Wagner, D. D. <strong>A mouse model of severe von Willebrand disease: defects in hemostasis and thrombosis.</strong> Proc. Nat. Acad. Sci. 95: 9524-9529, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9689113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9689113</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9689113[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.95.16.9524" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9689113">Denis et al. (1998)</a> concluded that these mice very closely mimic severe human von Willebrand disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9689113" 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="#35" class="mim-tip-reference" title="Golder, M., Pruss, C. M., Hegadorn, C., Mewburn, J., Laverty, K., Sponagle, K., Lillicrap, D. <strong>Mutation-specific hemostatic variability in mice expressing common type 2B von Willebrand disease substitutions.</strong> Blood 115: 4862-4869, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20371742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20371742</a>] [<a href="https://doi.org/10.1182/blood-2009-11-253120" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20371742">Golder et al. (2010)</a> generated transgenic mouse models of VWD type 2B by introducing mutations R1306W (<a href="#0005">613160.0005</a>), V1316M (<a href="#0007">613160.0007</a>), and R1341Q (<a href="#0008">613160.0008</a>) into the murine Vwf gene. The mutant Vwf proteins were expressed by the liver and only present in the plasma compartment, not in platelets. Mutant mice showed variable thrombocytopenia, which was most severe in V1316M mice. Blood smears from mutant mice showed many platelet aggregates, which were not seen in wildtype mice, and plasma samples from mutant mice showed decreased numbers of Vwf multimers resulting from increased Adamts13-mediated proteolysis. Mice with the V1316M mutation also had large platelets. Even though the enhanced affinity of Vwf 2B mutant proteins to platelets could theoretically have a thrombotic effect, ferric chloride-induced injury to cremaster arterioles in mutant mice showed a marked reduction in thrombus development and platelet adhesion in the presence of circulating Vwf 2B. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20371742" 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="#75" class="mim-tip-reference" title="Rayes, J., Hollestelle, M. J., Legendre, P., Marx, I., de Groot, P. G., Christophe, O. D., Lenting, P. J., Denis, C. V. <strong>Mutation and ADAMTS13-dependent modulation of disease severity in a mouse model for von Willebrand disease type 2B.</strong> Blood 115: 4870-4877, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20200350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20200350</a>] [<a href="https://doi.org/10.1182/blood-2009-11-254193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20200350">Rayes et al. (2010)</a> also generated mouse models of VWD type 2B by introducing the R1306Q and V1316M mutations in the murine Vwf gene. Both mutant proteins were associated with enhanced ristocetin-induced platelet aggregation, and mutant mice developed thrombocytopenia and circulating platelet aggregates, both of which were more pronounced for mice with the V1316M mutation. Only the V1316M mutant showed spontaneous platelet aggregation in vitro. Blood smears from mutant mice showed increased platelet size compared to wildtype. Both mutant proteins had a 2- to 3-fold reduced half-life and induced a 3- to 6-fold increase in number of giant platelets compared with wild-type Vwf. Loss of large multimers was observed in 50% of mutant mice. In vivo hemostatic potential of both mutants was severely impaired, even in an thrombotic model of arterial vessel occlusion. Mice who were doubly mutant for Vwf 2B and Adamts13 deficiency had more and larger circulating platelet aggregates and did not lack high molecular weight (HMW) multimers. The findings confirmed that VWD type 2B is dependent upon the type of mutation and pointed to an important role for ADAMTS13 in modulating platelet size as well as the removal of HMW VWF. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20200350" 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>42 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/613160" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=613160[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 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, ILE1628THR
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61750584 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750584;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=rs61750584" 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=rs61750584" 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=RCV000000308 OR RCV000086808 OR RCV000778377 OR RCV002243602 OR RCV004739270" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000308, RCV000086808, RCV000778377, RCV002243602, RCV004739270" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000308...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated ILE865THR is now designated ILE1628THR (I1628T). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a family with von Willebrand disease type 2A (see <a href="/entry/613554">613554</a>), <a href="#46" class="mim-tip-reference" title="Iannuzzi, M. C., Hidaka, N., Boehnke, M., Bruck, M. E., Hanna, W. T., Collins, F. S., Ginsburg, D. <strong>Analysis of the relationship of von Willebrand disease (vWD) and hereditary hemorrhagic telangiectasia and identification of a potential type IIA vWD mutation (ile865-to-thr).</strong> Am. J. Hum. Genet. 48: 757-763, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1673047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1673047</a>]" pmid="1673047">Iannuzzi et al. (1991)</a> identified a 4883T-C transition in the VWF gene, resulting in an ile865-to-thr (I865T) substitution. Type 2A VWD is characterized by a qualitative defect in VWF, resulting in the absence of large and intermediate VWF multimers, which may be caused by increased VWF proteolysis. The I865T substitution was located immediately adjacent to 2 other previously identified mutations that also result in type 2A von Willebrand disease (R834W, <a href="#0002">613160.0002</a> and V844D, <a href="#0003">613160.0003</a>), suggesting a clustering for these mutations in a portion of the protein critical for proteolysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1673047" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Dent, J. A., Berkowitz, S. D., Ware, J., Kasper, C. K., Ruggeri, Z. M. <strong>Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor.</strong> Proc. Nat. Acad. Sci. 87: 6306-6310, 1990. Note: Erratum: Proc. Nat. Acad. Sci. 87: 9508 only, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2385594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2385594</a>] [<a href="https://doi.org/10.1073/pnas.87.16.6306" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2385594">Dent et al. (1990)</a> noted that the I865T, R834W, and V844D mutations are located within a 32-amino acid segment in the midportion of the 2,813-amino acid VWF coding sequence. Type IIA von Willebrand disease is characterized by normal or only moderately decreased levels of von Willebrand factor, the absence of large and intermediate VWF multimers, and increased VWF proteolysis with an increase in the plasma levels of the 176-kD VWF proteolytic fragment. The proteolytic cleavage site is located between tyr842 and met843. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2385594" 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 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, ARG1597TRP
|
|
</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> rs61750117 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750117;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/rs61750117?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=rs61750117" 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=rs61750117" 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=RCV000000309 OR RCV000086797 OR RCV000623564 OR RCV000851942 OR RCV000999877 OR RCV002243603" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000309, RCV000086797, RCV000623564, RCV000851942, RCV000999877, RCV002243603" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000309...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated ARG834TRP is now designated ARG1597TRP (R1597W). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with von Willebrand disease type 2A (see <a href="/entry/613554">613554</a>), characterized by selective loss of high molecular weight VWF multimers, <a href="#32" class="mim-tip-reference" title="Ginsburg, D., Konkle, B. A., Gill, J. C., Montgomery, R. R., Bockenstedt, P. L., Johnson, T. A., Yang, A. Y. <strong>Molecular basis of human von Willebrand disease: analysis of platelet von Willebrand factor mRNA.</strong> Proc. Nat. Acad. Sci. 86: 3723-3727, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2786201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2786201</a>] [<a href="https://doi.org/10.1073/pnas.86.10.3723" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2786201">Ginsburg et al. (1989)</a> identified a heterozygous 4789C-T transition in the VWF gene, resulting in an arg834-to-trp (R834W) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2786201" 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 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, VAL1607ASP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61750579 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750579;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=rs61750579" 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=rs61750579" 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=RCV000000310 OR RCV000086803 OR RCV002243604" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000310, RCV000086803, RCV002243604" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000310...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated VAL844ASP is now designated VAL1607ASP (V1607D). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with von Willebrand disease type 2A (see <a href="/entry/613554">613554</a>), characterized by selective loss of high molecular weight VWF multimers, <a href="#32" class="mim-tip-reference" title="Ginsburg, D., Konkle, B. A., Gill, J. C., Montgomery, R. R., Bockenstedt, P. L., Johnson, T. A., Yang, A. Y. <strong>Molecular basis of human von Willebrand disease: analysis of platelet von Willebrand factor mRNA.</strong> Proc. Nat. Acad. Sci. 86: 3723-3727, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2786201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2786201</a>] [<a href="https://doi.org/10.1073/pnas.86.10.3723" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2786201">Ginsburg et al. (1989)</a> identified a heterozygous 4820T-A transversion in the VWF gene, resulting in a val844-to-asp (V844D) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2786201" 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 VON WILLEBRAND DISEASE, TYPE 2B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, TRP1313CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61749392 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61749392;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=rs61749392" 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=rs61749392" 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=RCV000000311 OR RCV000086709" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000311, RCV000086709" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000311...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated TRP550CYS is now designated TRP1313CYS (W1313C). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In the patient identified as case 7 in the report by <a href="#49" class="mim-tip-reference" title="Kyrle, P. A., Niessner, H., Dent, J., Panzer, S., Brenner, B., Zimmerman, T. S., Lechner, K. <strong>IIB von Willebrand's disease: pathogenetic and therapeutic studies.</strong> Brit. J. Haemat. 69: 55-59, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3132965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3132965</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1988.tb07602.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3132965">Kyrle et al. (1988)</a> with laboratory findings consistent with the diagnosis of type 2B von Willebrand disease (see <a href="/entry/613554">613554</a>), <a href="#101" class="mim-tip-reference" title="Ware, J., Dent, J. A., Azuma, H., Sugimoto, M., Kyrle, P. A., Yoshioka, A., Ruggeri, Z. M. <strong>Identification of a point mutation in type IIB von Willebrand disease illustrating the regulation of von Willebrand factor affinity for the platelet membrane glycoprotein Ib-IX receptor.</strong> Proc. Nat. Acad. Sci. 88: 2946-2950, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2011604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2011604</a>] [<a href="https://doi.org/10.1073/pnas.88.7.2946" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2011604">Ware et al. (1991)</a> found a trp550-to-cys (W550C) substitution. The mutation is located in the domain of the molecule comprising residues 449 to 728 involved in the binding to platelet glycoprotein Ib-IX receptor complex (see <a href="/entry/606672">606672</a>). This interaction is physiologically regulated so that it does not occur between circulating VWF and platelets but, rather, only at a site of vascular injury. The abnormal VWF found in type 2B von Willebrand disease has a characteristically increased affinity for GP Ib and binds to the circulating platelets. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3132965+2011604" 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 VON WILLEBRAND DISEASE, TYPE 2B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, ARG1306TRP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61749384 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61749384;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=rs61749384" 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=rs61749384" 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=RCV000000312 OR RCV000086699 OR RCV000851599 OR RCV000851989 OR RCV000851990 OR RCV005007800" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000312, RCV000086699, RCV000851599, RCV000851989, RCV000851990, RCV005007800" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000312...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated ARG543TRP is now designated ARG1306TRP (R1306W). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" 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 VWD type 2B (see <a href="/entry/613554">613554</a>), <a href="#73" class="mim-tip-reference" title="Randi, A. M., Rabinowitz, I., Mancuso, D. J., Mannucci, P. M., Sadler, J. E. <strong>Molecular basis of von Willebrand disease type IIB: candidate mutations cluster in one disulfide loop between proposed platelet glycoprotein Ib binding sequences.</strong> J. Clin. Invest. 87: 1220-1226, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2010538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2010538</a>] [<a href="https://doi.org/10.1172/JCI115122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2010538">Randi et al. (1991)</a> identified a heterozygous 4166C-T transition in exon 28 of the VWF gene, resulting in an arg543-to-trp (R543W) substitution in the domain that interacts with platelet glycoprotein GP1BA (<a href="/entry/606672">606672</a>). Both patients had previously been reported by <a href="#79" class="mim-tip-reference" title="Ruggeri, Z. M., Pareti, F. I., Mannucci, P. M., Ciavarella, N., Zimmerman, T. S. <strong>Heightened interaction between platelets and factor VIII von Willebrand factor in a new subtype of von Willebrand's disease.</strong> New Eng. J. Med. 302: 1047-1051, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6767976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6767976</a>] [<a href="https://doi.org/10.1056/NEJM198005083021902" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6767976">Ruggeri et al. (1980)</a> as having VWD with a heightened interaction between platelets and VWF. Patient plasma showed a decrease in large VWF multimers due to spontaneous binding of VWF to platelets and subsequent clearance from the circulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6767976+2010538" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Donner, M., Kristoffersson, A. C., Lenk, H., Scheibel, E., Dahlback, B., Nilsson, I. M., Holmberg, L. <strong>Type IIB von Willebrand's disease: gene mutations and clinical presentation in nine families from Denmark, Germany and Sweden.</strong> Brit. J. Haemat. 82: 58-65, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1419803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1419803</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1992.tb04594.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1419803">Donner et al. (1992)</a> studied 20 patients from 9 unrelated families with type 2B VWD from Denmark, Germany, and Sweden. Fifteen patients in 5 families were heterozygous for the R543W mutation. In 2 of the 5 families, it represented a de novo mutation. In one of the other families, the father, though asymptomatic and with normal laboratory test results, carried the mutation in heterozygous form. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1419803" 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 VON WILLEBRAND DISEASE, TYPE 2B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, ARG1308CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61749387 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61749387;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=rs61749387" 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=rs61749387" 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=RCV000000313 OR RCV000086703 OR RCV000851770 OR RCV002225253" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000313, RCV000086703, RCV000851770, RCV002225253" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000313...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated ARG545CYS is now designated ARG1308CYS (R1308C). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" 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 7 patients from 4 unrelated families with VWD type 2B (see <a href="/entry/613554">613554</a>), <a href="#73" class="mim-tip-reference" title="Randi, A. M., Rabinowitz, I., Mancuso, D. J., Mannucci, P. M., Sadler, J. E. <strong>Molecular basis of von Willebrand disease type IIB: candidate mutations cluster in one disulfide loop between proposed platelet glycoprotein Ib binding sequences.</strong> J. Clin. Invest. 87: 1220-1226, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2010538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2010538</a>] [<a href="https://doi.org/10.1172/JCI115122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2010538">Randi et al. (1991)</a> identified a heterozygous 4172C-T transition in exon 28 of the VWF gene, resulting in an arg545-to-cys (R545C) substitution in the domain that interacts with platelet glycoprotein GP1BA (<a href="/entry/606672">606672</a>). Patient plasma showed a decrease in large VWF multimers due to spontaneous binding of VWF to platelets and subsequent clearance from the circulation. Examination of the RFLP haplotype background for the R545C mutations identified in their study permitted <a href="#73" class="mim-tip-reference" title="Randi, A. M., Rabinowitz, I., Mancuso, D. J., Mannucci, P. M., Sadler, J. E. <strong>Molecular basis of von Willebrand disease type IIB: candidate mutations cluster in one disulfide loop between proposed platelet glycoprotein Ib binding sequences.</strong> J. Clin. Invest. 87: 1220-1226, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2010538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2010538</a>] [<a href="https://doi.org/10.1172/JCI115122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2010538">Randi et al. (1991)</a> to conclude that the mutation had occurred independently 3 times; a fourth patient represented a new mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2010538" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Donner, M., Andersson, A.-M., Kristoffersson, A.-C., Nilsson, I. M., Dahlback, B., Holmberg, L. <strong>An arg545-to-cys substitution mutation of the von Willebrand factor in type IIB von Willebrand's disease.</strong> Europ. J. Haemat. 47: 342-345, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1761120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1761120</a>] [<a href="https://doi.org/10.1111/j.1600-0609.1991.tb01858.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1761120">Donner et al. (1991)</a> reported another family with this mutation. In a later study of 20 patients from 9 unrelated families with type 2B VWD from Denmark, Germany, and Sweden, <a href="#21" class="mim-tip-reference" title="Donner, M., Kristoffersson, A. C., Lenk, H., Scheibel, E., Dahlback, B., Nilsson, I. M., Holmberg, L. <strong>Type IIB von Willebrand's disease: gene mutations and clinical presentation in nine families from Denmark, Germany and Sweden.</strong> Brit. J. Haemat. 82: 58-65, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1419803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1419803</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1992.tb04594.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1419803">Donner et al. (1992)</a> found the arg545-to-cys mutation in heterozygous state in 4 affected persons in 3 families. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1761120+1419803" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a Japanese patient with VWD type 2B, <a href="#38" class="mim-tip-reference" title="Hagiwara, T., Inaba, H., Yoshida, S., Nagaizumi, K., Arai, M., Hanabusa, H., Fukutake, K. <strong>A novel mutation gly1672-to-arg in type 2A and a homozygous mutation in type 2B von Willebrand disease.</strong> Thromb. Haemost. 76: 253-257, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8865541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8865541</a>]" pmid="8865541">Hagiwara et al. (1996)</a> identified a homozygous mutation in exon 28 of the VWF gene, resulting in an arg1308-to-cys (R1308C) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8865541" 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 VON WILLEBRAND DISEASE, TYPE 2B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, VAL1316MET
|
|
</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> rs61749397 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61749397;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/rs61749397?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=rs61749397" 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=rs61749397" 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=RCV000000314 OR RCV000086715 OR RCV000507168 OR RCV000678767 OR RCV000851771 OR RCV002476901" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000314, RCV000086715, RCV000507168, RCV000678767, RCV000851771, RCV002476901" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000314...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated VAL553MET is now designated VAL1316MET (V1316M). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with VWD type 2B (see <a href="/entry/613554">613554</a>), <a href="#73" class="mim-tip-reference" title="Randi, A. M., Rabinowitz, I., Mancuso, D. J., Mannucci, P. M., Sadler, J. E. <strong>Molecular basis of von Willebrand disease type IIB: candidate mutations cluster in one disulfide loop between proposed platelet glycoprotein Ib binding sequences.</strong> J. Clin. Invest. 87: 1220-1226, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2010538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2010538</a>] [<a href="https://doi.org/10.1172/JCI115122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2010538">Randi et al. (1991)</a> identified a heterozygous 4196G-A transition in exon 28 of the VWF gene, resulting in a val553-to-met (V553M) substitution in the domain that interacts with platelet glycoprotein GP1BA (<a href="/entry/606672">606672</a>). Patient plasma showed a decrease in large VWF multimers due to spontaneous binding of VWF to platelets and subsequent clearance from the circulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2010538" 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="#64" class="mim-tip-reference" title="Murray, E. W., Giles, A. R., Lillicrap, D. <strong>Germ-line mosaicism for a valine-to-methionine substitution at residue 553 in the glycoprotein Ib-binding domain of von Willebrand factor, causing type IIB von Willebrand disease.</strong> Am. J. Hum. Genet. 50: 199-207, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1729889/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1729889</a>]" pmid="1729889">Murray et al. (1992)</a> also observed this mutation in multiple members of a family with type 2B von Willebrand disease. They showed by VWF polymorphism analysis that the mutation originated in a VWF gene transmitted from a phenotypically normal grandfather. Analysis of the sperm from this individual showed that approximately 5% of the germline contained the mutant sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1729889" 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="#47" class="mim-tip-reference" title="Jackson, S. C., Sinclair, G. D., Cloutier, S., Duan, Z., Rand, M. L., Poon, M.-C. <strong>The Montreal platelet syndrome kindred has type 2B von Willebrand disease with the VWF V1316M mutation.</strong> Blood 113: 3348-3351, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19060241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19060241</a>] [<a href="https://doi.org/10.1182/blood-2008-06-165233" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19060241">Jackson et al. (2009)</a> identified a heterozygous V1316M substitution in affected members of a large French Canadian family with VWD type 2B that was described by <a href="#63" class="mim-tip-reference" title="Milton, J. G., Frojmovic, M. M., Tang, S. S., White, J. G. <strong>Spontaneous platelet aggregation in a hereditary giant platelet syndrome (MPS).</strong> Am. J. Path. 114: 336-345, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6696046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6696046</a>]" pmid="6696046">Milton et al. (1984)</a> as having the 'Montreal platelet syndrome.' Affected individuals had lifelong bruising; some patients had severe postoperative bleeding, postpartum hemorrhage, and gastrointestinal bleeding. A significant proportion of platelets occurred in microaggregates typically containing 2 to 6 platelets, and the aggregation could be increased by stirring. Affected family members had macrothrombocytopenia, borderline to normal VWF antigen, low ristocetin cofactor activity, and normal factor VIII coagulant activity, all consistent with VWD type 2B. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6696046+19060241" 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 VON WILLEBRAND DISEASE, TYPE 2B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, ARG1341GLN
|
|
</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> rs61749403 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61749403;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/rs61749403?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=rs61749403" 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=rs61749403" 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=RCV000000315 OR RCV000086721 OR RCV002227435 OR RCV002243605 OR RCV004547443" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000315, RCV000086721, RCV002227435, RCV002243605, RCV004547443" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000315...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated ARG578GLN is now designated ARG1341GLN (R1341Q). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with VWD type 2B (see <a href="/entry/613554">613554</a>), <a href="#15" class="mim-tip-reference" title="Cooney, K. A., Nichols, W. C., Bruck, M. E., Bahou, W. F., Shapiro, A. D., Bowie, E. J. W., Gralnick, H. R., Ginsburg, D. <strong>The molecular defect in type IIB von Willebrand disease: identification of four potential missense mutations within the putative GpIb binding domain.</strong> J. Clin. Invest. 87: 1227-1233, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1672694/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1672694</a>] [<a href="https://doi.org/10.1172/JCI115123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1672694">Cooney et al. (1991)</a> identified a heterozygous 4022G-A transition in the VWF gene, resulting in an arg578-to-gln (R578Q) substitution within the putative GP1BA (<a href="/entry/606672">606672</a>)-binding domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1672694" 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 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, SER1613PRO
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61750581 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750581;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=rs61750581" 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=rs61750581" 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=RCV000000316 OR RCV000086805" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000316, RCV000086805" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000316...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated SER850PRO is now designated SER1613PRO (S1613P). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#73" class="mim-tip-reference" title="Randi, A. M., Rabinowitz, I., Mancuso, D. J., Mannucci, P. M., Sadler, J. E. <strong>Molecular basis of von Willebrand disease type IIB: candidate mutations cluster in one disulfide loop between proposed platelet glycoprotein Ib binding sequences.</strong> J. Clin. Invest. 87: 1220-1226, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2010538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2010538</a>] [<a href="https://doi.org/10.1172/JCI115122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2010538">Randi et al. (1991)</a> suggested that mutations causing type IIA von Willebrand disease are clustered in the A2 domain of the VWF gene. The ser850-to-pro (S850P) mutation, designated S1613P based on a different numbering system, is in the A2 region of the gene (<a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve, 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20409624+2010538" 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><div class="mim-changed mim-change">.0010 VWF POLYMORPHISM</div></strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, ARG1399HIS
|
|
</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> rs1800382 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1800382;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/rs1800382?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=rs1800382" 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=rs1800382" 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=RCV000756907 OR RCV000851940 OR RCV001270629 OR RCV002243606 OR RCV003234883 OR RCV003447466 OR RCV004547444" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000756907, RCV000851940, RCV001270629, RCV002243606, RCV003234883, RCV003447466, RCV004547444" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000756907...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the polymorphism originally designated ARG636HIS is now designated ARG1399HIS (R1399H). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" 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="Cooney, K. A., Nichols, W. C., Bruck, M. E., Bahou, W. F., Shapiro, A. D., Bowie, E. J. W., Gralnick, H. R., Ginsburg, D. <strong>The molecular defect in type IIB von Willebrand disease: identification of four potential missense mutations within the putative GpIb binding domain.</strong> J. Clin. Invest. 87: 1227-1233, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1672694/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1672694</a>] [<a href="https://doi.org/10.1172/JCI115123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1672694">Cooney et al. (1991)</a> found a rare sequence polymorphism at nucleotide 4196 of the VWF gene. A 4196G-A transition led to an arg636-to-his (R636H) substitution. The allele frequency was estimated to be about 0.015. Although the change was within the region involved in binding to platelet glycoprotein receptor and the region mutant in von Willebrand disease type 2B (see <a href="/entry/613554">613554</a>), no hematologic abnormality was associated with the change. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1672694" 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 VON WILLEBRAND DISEASE, TYPE 2N</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, THR791MET
|
|
</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> rs61748477 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61748477;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/rs61748477?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=rs61748477" 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=rs61748477" 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=RCV000000318 OR RCV000086606 OR RCV000851745 OR RCV002227436 OR RCV002264633" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000318, RCV000086606, RCV000851745, RCV002227436, RCV002264633" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000318...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated THR28MET is now designated THR791MET (T791M). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 50-year-old French woman, born of consanguineous parents, with the Normandy type of VWD (VWD2N; see <a href="/entry/613554">613554</a>) reported by <a href="#57" class="mim-tip-reference" title="Mazurier, C., Dieval, J., Jorieux, S., Delobel, J., Goudemand, M. <strong>A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF: characterization of abnormal vWF/FVIII interaction.</strong> Blood 75: 20-26, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2104761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2104761</a>]" pmid="2104761">Mazurier et al. (1990)</a>, <a href="#29" class="mim-tip-reference" title="Gaucher, C., Jorieux, S., Mercier, B., Oufkir, D., Mazurier, C. <strong>The 'Normandy' variant of von Willebrand disease: characterization of a point mutation in the von Willebrand factor gene.</strong> Blood 77: 1937-1941, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2018834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2018834</a>]" pmid="2018834">Gaucher et al. (1991)</a> identified a homozygous 791C-T transition in exon 18 of the VWF gene, resulting in a thr28-to-met (T28M) substitution in the mature VWF subunit. The woman had a lifelong history of excessive bleeding, and laboratory data showed decreased factor VIII (<a href="/entry/300841">300841</a>), subnormal bleeding time, and normal VWF multimers. VWF isolated from patient plasma was unable to bind factor VIII. <a href="#29" class="mim-tip-reference" title="Gaucher, C., Jorieux, S., Mercier, B., Oufkir, D., Mazurier, C. <strong>The 'Normandy' variant of von Willebrand disease: characterization of a point mutation in the von Willebrand factor gene.</strong> Blood 77: 1937-1941, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2018834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2018834</a>]" pmid="2018834">Gaucher et al. (1991)</a> noted that the phenotype resembled hemophilia A, or F8 deficiency, but showed autosomal recessive instead of X-linked inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2104761+2018834" 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 functional expression studies, <a href="#96" class="mim-tip-reference" title="Tuley, E. A., Gaucher, C., Jorieux, S., Worrall, N. K., Sadler, J. E., Mazurier, C. <strong>Expression of von Willebrand factor 'Normandy': an autosomal mutation that mimics hemophilia A.</strong> Proc. Nat. Acad. Sci. 88: 6377-6381, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1906179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1906179</a>] [<a href="https://doi.org/10.1073/pnas.88.14.6377" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1906179">Tuley et al. (1991)</a> showed that the T28M mutation occurred in the factor VIII binding site of the VWF molecule. The corresponding mutant recombinant molecule formed normal multimers and had normal ristocetin cofactor activity, but had a defect in factor VIII binding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1906179" 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="#103" class="mim-tip-reference" title="Wise, R. J., Ewenstein, B. M., Gorlin, J., Narins, S. C., Jesson, M., Handin, R. I. <strong>Autosomal recessive transmission of hemophilia A due to a von Willebrand factor mutation.</strong> Hum. Genet. 91: 367-372, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8500791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8500791</a>] [<a href="https://doi.org/10.1007/BF00217358" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8500791">Wise et al. (1993)</a> reported a family with VWD type 2N ascertained through a female patient with low levels of factor VIII activity. The patient was homozygous for the thr28-to-met mutation, which was heterozygous in both parents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8500791" 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 VON WILLEBRAND DISEASE, TYPE 2N</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, ARG816TRP
|
|
</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> rs121964894 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964894;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/rs121964894?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=rs121964894" 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=rs121964894" 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=RCV000000319 OR RCV000086613 OR RCV001195286 OR RCV004795363" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000319, RCV000086613, RCV001195286, RCV004795363" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000319...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated ARG53TRP is now designated ARG816TRP (R816W). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a family with the Normandy type of von Willebrand disease (VWD2N; see <a href="/entry/613554">613554</a>), <a href="#30" class="mim-tip-reference" title="Gaucher, C., Mercier, B., Jorieux, S., Oufkir, D., Mazurier, C. <strong>Identification of two point mutations in the von Willebrand factor gene of three families with the 'Normandy' variant of von Willebrand disease.</strong> Brit. J. Haemat. 78: 506-514, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1832934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1832934</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1991.tb04480.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1832934">Gaucher et al. (1991)</a> demonstrated homozygosity for a C-to-T transition resulting in an arg53-to-trp (R53W) substitution in the mature protein. Although there was no known parental consanguinity, both parents originated from the same village in Portugal. The 2 alleles showed sequence variation within the intron 40 VNTR and might have arisen after the arg53-to-trp mutation occurred. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1832934" 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 VON WILLEBRAND DISEASE, TYPE 2N</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
VON WILLEBRAND DISEASE, TYPE 1, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, ARG854GLN
|
|
</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> rs41276738 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs41276738;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/rs41276738?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=rs41276738" 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=rs41276738" 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=RCV000000320 OR RCV000000321 OR RCV000086620 OR RCV000169683 OR RCV000336497 OR RCV000762901 OR RCV000851593 OR RCV001270529 OR RCV003987302 OR RCV004547445 OR RCV004771452" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000320, RCV000000321, RCV000086620, RCV000169683, RCV000336497, RCV000762901, RCV000851593, RCV001270529, RCV003987302, RCV004547445, RCV004771452" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000320...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated ARG91GLN is now designated ARG854GLN (R854Q). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with the Normandy type of von Willebrand disease (VWD2N; see <a href="/entry/613554">613554</a>), <a href="#30" class="mim-tip-reference" title="Gaucher, C., Mercier, B., Jorieux, S., Oufkir, D., Mazurier, C. <strong>Identification of two point mutations in the von Willebrand factor gene of three families with the 'Normandy' variant of von Willebrand disease.</strong> Brit. J. Haemat. 78: 506-514, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1832934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1832934</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1991.tb04480.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1832934">Gaucher et al. (1991)</a> demonstrated compound heterozygosity for the arg53-to-trp mutation (<a href="/entry/193400#0012">193400.0012</a>) and another C-to-T transition that resulted in a substitution of glutamine for arginine-91. The patient's parents were related as second cousins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1832934" 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="#39" class="mim-tip-reference" title="Hilbert, L., Jorieux, S., Fontenay-Roupie, M., Guicheteau, M., Fressinaud, E., Meyer, D., Mazurier, C., the INSERM Network on Molecular Abnormalities in von Willebrand Disease. <strong>Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene.</strong> Brit. J. Haemat. 127: 184-189, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15461624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15461624</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2004.05187.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15461624">Hilbert et al. (2004)</a> reported 2 unrelated French patients with type 2N VWD who were compound heterozygous for R854Q and another pathogenic mutation (Y795C, <a href="#0031">613160.0031</a> and C804F, <a href="#0032">613160.0032</a>, respectively). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15461624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#71" class="mim-tip-reference" title="Peerlinck, K., Eikenboom, J. C. J., Ploos Van Amstel, H. K., Sangtawesin, W., Arnout, J., Reitsma, P. H., Vermylen, J., Briet, E. <strong>A patient with von Willebrand's disease characterized by a compound heterozygosity for a substitution of arg-854 by gln in the putative factor-VIII-binding domain of von Willebrand factor (vWF) on one allele and very low levels of mRNA from the second vWF allele.</strong> Brit. J. Haemat. 80: 358-363, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1581215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1581215</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1992.tb08145.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1581215">Peerlinck et al. (1992)</a> identified a heterozygous A-to-G transition in exon 20 of the VWF gene, resulting in an arg854-to-gln (R854Q) substitution, in a 23-year-old woman with a lifelong history of bleeding and low VWF levels, consistent with von Willebrand disease type 1 (<a href="/entry/193400">193400</a>). Laboratory studies showed disproportionately low factor VIII (F8; <a href="/entry/300841">300841</a>) and decreased binding capacity of VWF for F8. The R854Q substitution occurred in the putative factor VIII-binding domain. All VWF multimers were normal. Neither parent was clinically affected, but laboratory studies showed that the father had partially increased bleeding time and partially decreased VWF antigen. Restriction enzyme analysis indicated that the unaffected mother was also heterozygous for the R854Q mutation, and that the patient had inherited a hypomorphic 'silent' VWF allele from her father. <a href="#71" class="mim-tip-reference" title="Peerlinck, K., Eikenboom, J. C. J., Ploos Van Amstel, H. K., Sangtawesin, W., Arnout, J., Reitsma, P. H., Vermylen, J., Briet, E. <strong>A patient with von Willebrand's disease characterized by a compound heterozygosity for a substitution of arg-854 by gln in the putative factor-VIII-binding domain of von Willebrand factor (vWF) on one allele and very low levels of mRNA from the second vWF allele.</strong> Brit. J. Haemat. 80: 358-363, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1581215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1581215</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1992.tb08145.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1581215">Peerlinck et al. (1992)</a> noted that the inheritance pattern in this family was difficult to determine, but concluded that the presence of the 'silent' allele allowed the clinical expression of the mutated second allele, resulting in a recessive phenotype in the proband. <a href="#71" class="mim-tip-reference" title="Peerlinck, K., Eikenboom, J. C. J., Ploos Van Amstel, H. K., Sangtawesin, W., Arnout, J., Reitsma, P. H., Vermylen, J., Briet, E. <strong>A patient with von Willebrand's disease characterized by a compound heterozygosity for a substitution of arg-854 by gln in the putative factor-VIII-binding domain of von Willebrand factor (vWF) on one allele and very low levels of mRNA from the second vWF allele.</strong> Brit. J. Haemat. 80: 358-363, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1581215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1581215</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1992.tb08145.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1581215">Peerlinck et al. (1992)</a> commented that although the phenotype was similar to that of the 'Normandy' type 2N variant (see <a href="/entry/613554">613554</a>), the patient also had quantitatively low VWF and was thus classified as having VWD type 1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1581215" 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 MOVED TO <a href="/entry/613160#0013">613160.0013</a></strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0015" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 VON WILLEBRAND DISEASE, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
VON WILLEBRAND DISEASE, TYPE 1, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, ARG1659TER
|
|
</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> rs61750595 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750595;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/rs61750595?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=rs61750595" 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=rs61750595" 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=RCV000000322 OR RCV000000323 OR RCV000086820 OR RCV002227437 OR RCV004739271" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000322, RCV000000323, RCV000086820, RCV002227437, RCV004739271" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000322...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with von Willebrand disease type 3 (<a href="/entry/277480">277480</a>), <a href="#108" class="mim-tip-reference" title="Zhang, Z. P., Falk, G., Blomback, M., Egberg, N., Anvret, M. <strong>Identification of a new nonsense mutation in the von Willebrand factor gene in patients with von Willebrand disease type III.</strong> Hum. Molec. Genet. 1: 61-62, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301136</a>] [<a href="https://doi.org/10.1093/hmg/1.1.61" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301136">Zhang et al. (1992)</a> identified a homozygous C-to-T transition in exon 28 of the VWF gene, resulting in an arg1659-to-ter (R1659X) substitution. Both parents carried the heterozygous mutation; the clinical features of the family were not reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301136" 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="#109" class="mim-tip-reference" title="Zhang, Z. P., Lindstedt, M., Falk, G., Blomback, M., Egberg, N., Anvret, M. <strong>Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I.</strong> Am. J. Hum. Genet. 51: 850-858, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1415226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1415226</a>]" pmid="1415226">Zhang et al. (1992)</a> identified the R1659X mutation in affected members of 3 families from western Finland with VWD type 3. Severely affected individuals were either homozygous or presumed to be compound heterozygous with another pathogenic mutation. In 1 family, heterozygous mutation carriers had a less severe phenotype, consistent with type 1 VWD (<a href="/entry/193400">193400</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1415226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0016" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 VON WILLEBRAND DISEASE, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
VON WILLEBRAND DISEASE, TYPE 1, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, ARG1852TER
|
|
</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> rs61750612 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750612;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/rs61750612?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=rs61750612" 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=rs61750612" 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=RCV000000324 OR RCV000000325 OR RCV000086843 OR RCV000851820 OR RCV001813924 OR RCV003447467 OR RCV004547446" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000324, RCV000000325, RCV000086843, RCV000851820, RCV001813924, RCV003447467, RCV004547446" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000324...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Swedish patient with VWD type 3 (<a href="/entry/277480">277480</a>) and pronounced bleeding tendency, <a href="#109" class="mim-tip-reference" title="Zhang, Z. P., Lindstedt, M., Falk, G., Blomback, M., Egberg, N., Anvret, M. <strong>Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I.</strong> Am. J. Hum. Genet. 51: 850-858, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1415226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1415226</a>]" pmid="1415226">Zhang et al. (1992)</a> identified homozygous C-to-T transition in exon 32 of the VWF gene, resulting in an arg1852-to-ter (R1852X) substitution. Two additional Swedish patients with type 3 were heterozygous for the mutation, but were predicted to be compound heterozygous for another mutation because their phenotype was more severe than other family members, who had type 1 disease (<a href="/entry/193400">193400</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1415226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0017" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 VON WILLEBRAND DISEASE, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, ARG2635TER
|
|
</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> rs61751296 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61751296;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/rs61751296?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=rs61751296" 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=rs61751296" 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=RCV000000326 OR RCV000086892 OR RCV002227438 OR RCV002264634" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000326, RCV000086892, RCV002227438, RCV002264634" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000326...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe VMD type 3 (<a href="/entry/277480">277480</a>), <a href="#109" class="mim-tip-reference" title="Zhang, Z. P., Lindstedt, M., Falk, G., Blomback, M., Egberg, N., Anvret, M. <strong>Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I.</strong> Am. J. Hum. Genet. 51: 850-858, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1415226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1415226</a>]" pmid="1415226">Zhang et al. (1992)</a> identified a C-to-T transition in exon 45 of the VWF gene, resulting in an arg2635-to-ter (R2635X) substitution. Although the patient was heterozygous for this mutation, he was thought to be a compound heterozygote for another, as yet unidentified mutation, since he had severe disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1415226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0018" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 VON WILLEBRAND DISEASE, TYPE 2M</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, GLY1324SER
|
|
</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> rs61749398 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61749398;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/rs61749398?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=rs61749398" 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=rs61749398" 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=RCV000000327 OR RCV000086716 OR RCV003447468" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000327, RCV000086716, RCV003447468" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000327...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated GLY561SER is now designated GLY1324SER (G1324S). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with VWD type 2M (see <a href="/entry/613554">613554</a>), <a href="#72" class="mim-tip-reference" title="Rabinowitz, I., Tuley, E. A., Mancuso, D. J., Randi, A. M., Firkin, B. G., Howard, M. A., Sadler, J. E. <strong>Von Willebrand disease type B: a missense mutation selectively abolishes ristocetin-induced von Willebrand factor binding to platelet glycoprotein Ib.</strong> Proc. Nat. Acad. Sci. 89: 9846-9849, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1409710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1409710</a>] [<a href="https://doi.org/10.1073/pnas.89.20.9846" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1409710">Rabinowitz et al. (1992)</a> identified a heterozygous mutation in exon 28 of the VWF gene, resulting in a gly561-to-ser (G561S) substitution within the GP1BA (<a href="/entry/606672">606672</a>)-binding domain of the mature protein. Laboratory studies of patient plasma showed normal botrocetin-induced binding but no ristocetin-induced binding to platelet glycoprotein Ib. The patient's plasma VWF contained a full range of multimers. The mutant recombinant protein formed normal multimers, but exhibited the same functional defect as the patient's plasma VWF. The patient was originally described by <a href="#43" class="mim-tip-reference" title="Howard, M. A., Perkin, J., Salem, H. H., Firkin, B. G. <strong>The agglutination of human platelets by botrocetin: evidence that botrocetin and ristocetin act at different sites on the factor VIII molecule and platelet membrane.</strong> Brit. J. Haemat. 57: 25-35, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6426499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6426499</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1984.tb02862.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6426499">Howard et al. (1984)</a> and <a href="#1" class="mim-tip-reference" title="Andrews, R. K., Booth, W. J., Gorman, J. J., Castaldi, P. A., Berndt, M. C. <strong>Purification of botrocetin from Bothrops jararaca venom: analysis of the botrocetin-mediated interaction between von Willebrand factor and the human platelet membrane glycoprotein Ib-IX complex.</strong> Biochemistry 28: 8317-8326, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2557900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2557900</a>] [<a href="https://doi.org/10.1021/bi00447a009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2557900">Andrews et al. (1989)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6426499+2557900+1409710" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0019" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, CYS1272ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61749372 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61749372;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=rs61749372" 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=rs61749372" 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=RCV000000328 OR RCV000086679 OR RCV002243607" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000328, RCV000086679, RCV002243607" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000328...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated CYS509ARG is now designated CYS1272ARG (C1272R). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with type 2A von Willebrand disease (see <a href="/entry/613554">613554</a>), <a href="#50" class="mim-tip-reference" title="Lavergne, J.-M., De Paillette, L., Bahnak, B. R., Ribba, A.-S., Fressinaud, E., Meyer, D., Pietu, G. <strong>Defects in type IIA von Willebrand disease: a cysteine 509 to arginine substitution in the mature von Willebrand factor disrupts a disulphide loop involved in the interaction with platelet glycoprotein Ib-IX.</strong> Brit. J. Haemat. 82: 66-72, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1419804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1419804</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1992.tb04595.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1419804">Lavergne et al. (1992)</a> found a 3814T-C transition in the 5-prime end of exon 28 of the VWF gene, resulting in a cys509-to-arg (C509R) substitution. This mutation eliminated an intramolecular disulfide bridge formed by cys509 and cys695. The bridge is important to maintenance of the configuration of VWF functional domains that interact with platelet glycoprotein Ib-IX. However, it appeared that this bridge also affects the processing and composition of VWF multimers, since the patient had a type 2A phenotype. The amino acid substitution was the result of a 381T-C transition. The findings suggested a broader pathogenic mechanism for VWF type 2A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1419804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0020" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 VON WILLEBRAND DISEASE, TYPE 2B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, VAL1314LEU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61749393 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61749393;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=rs61749393" 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=rs61749393" 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=RCV000000329 OR RCV000087017" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000329, RCV000087017" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000329...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated VAL551LEU is now designated VAL1314LEU (V1314L). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" 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 1 of 20 patients from 9 unrelated families with type 2B VWD (see <a href="/entry/613554">613554</a>) from Denmark, Germany, and Sweden, <a href="#21" class="mim-tip-reference" title="Donner, M., Kristoffersson, A. C., Lenk, H., Scheibel, E., Dahlback, B., Nilsson, I. M., Holmberg, L. <strong>Type IIB von Willebrand's disease: gene mutations and clinical presentation in nine families from Denmark, Germany and Sweden.</strong> Brit. J. Haemat. 82: 58-65, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1419803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1419803</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1992.tb04594.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1419803">Donner et al. (1992)</a> found heterozygosity for a de novo val551-to-leu (V551L) mutation. In most of the patients with type 2B VWD, spontaneous thrombocytopenia had been recorded on at least one occasion. The patient with the val551-to-leu substitution and 5 patients with the arg543-to-trp (<a href="#0005">613160.0005</a>) substitution had had bleeding associated with thrombocytopenia in the neonatal period or early infancy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1419803" 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="0021" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 VON WILLEBRAND DISEASE, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, 1-BP DEL, EX18, C
|
|
</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> rs62643632 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62643632;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/rs62643632?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=rs62643632" 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=rs62643632" 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=RCV000000330 OR RCV000086611 OR RCV000851752 OR RCV000852083 OR RCV002264635 OR RCV002476902 OR RCV005000978" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000330, RCV000086611, RCV000851752, RCV000852083, RCV002264635, RCV002476902, RCV005000978" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000330...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Among 24 patients with von Willebrand disease type 3 (<a href="/entry/277480">277480</a>), <a href="#107" class="mim-tip-reference" title="Zhang, Z. P., Falk, G., Blomback, M., Egberg, N., Anvret, M. <strong>A single cytosine deletion in exon 18 of the von Willebrand factor gene is the most common mutation in Swedish vWD type III patients.</strong> Hum. Molec. Genet. 1: 767-768, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1302613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1302613</a>] [<a href="https://doi.org/10.1093/hmg/1.9.767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1302613">Zhang et al. (1992)</a> found that 24 of the 48 chromosomes harbored a 1-bp deletion in a stretch of 6 cytosines at position 2679-2684 in exon 18 of the VWF gene. Nine patients were homozygous and 6 were heterozygous for the mutation. The deletion interrupted the reading frame and resulted in a translational stop codon at position V842 in the amino acid sequence. Translation of the mutant mRNA would yield only a severely truncated mature VWF (48 of 2,050 amino acids) after removal of the propeptide. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1302613" 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="#106" class="mim-tip-reference" title="Zhang, Z. P., Blomback, M., Nyman, D., Anvret, M. <strong>Mutations of von Willebrand factor gene in families with von Willebrand disease in the Aland Islands.</strong> Proc. Nat. Acad. Sci. 90: 7937-7940, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8367445/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8367445</a>] [<a href="https://doi.org/10.1073/pnas.90.17.7937" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8367445">Zhang et al. (1993)</a> demonstrated that deletion of 1 cytosine in exon 18 was the mutation in the Aland family (family S) in which the disease was first reported by <a href="#99" class="mim-tip-reference" title="von Willebrand, E. A. <strong>Hereditar pseudohemofili.</strong> Finska Lakar. Hand. 68: 87-112, 1926."None>von Willebrand (1926)</a>. They reported studies of descendants of the original family; only heterozygotes were found surviving. The proposita was a 5-year-old girl, who later bled to death during her fourth menstrual period. She had a normal coagulation time, but the bleeding time was prolonged, despite a normal platelet count. All but 1 of her 11 sibs had bleeding symptoms, as did both of her parents, who were third cousins, and many members of her family on both sides. Four of the proband's sisters had died of uncontrolled bleeding in early childhood; 3 died from gastrointestinal bleeding and 1 from bleeding after she bit her tongue in a fall. The predominant symptoms were bleeding from mucous membranes, such as from the nose, the gingivae after tooth extractions, the uterus, and the gastrointestinal tract. In contrast to hemophilia, hemarthroses seemed to be rare. All 5 of the girls who died from uncontrolled bleeding were probably homozygous for the deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8367445" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#60" class="mim-tip-reference" title="Mertes, G., Ludwig, M., Schwaab, R., Brackmann, H.-H., Olek, K. <strong>Delta C in exon 18 of the von Willebrand gene is uncommon in German vWD type III patients. (Letter)</strong> Thromb. Haemost. 70: 1064-1065, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8165603/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8165603</a>]" pmid="8165603">Mertes et al. (1993)</a> found that the single cytosine deletion in exon 18 observed in half the alleles of 24 Swedish VWD type 3 patients (<a href="#108" class="mim-tip-reference" title="Zhang, Z. P., Falk, G., Blomback, M., Egberg, N., Anvret, M. <strong>Identification of a new nonsense mutation in the von Willebrand factor gene in patients with von Willebrand disease type III.</strong> Hum. Molec. Genet. 1: 61-62, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301136</a>] [<a href="https://doi.org/10.1093/hmg/1.1.61" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301136">Zhang et al., 1992</a>) occurred uncommonly in German patients with type 3 VWD; only 1 out of 24 alleles carried the delta-C mutation. A founder effect might explain the higher frequency in Sweden. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8165603+1301136" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0022" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, PHE1514CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61750101 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750101;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=rs61750101" 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=rs61750101" 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=RCV000000331 OR RCV000086775" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000331, RCV000086775" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000331...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated PHE751CYS is now designated PHE1514CYS (F1514C). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" 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 8 patients from a large type 2A (see <a href="/entry/613554">613554</a>) von Willebrand disease family, <a href="#28" class="mim-tip-reference" title="Gaucher, C., Hanss, M., Dechavanne, M., Mazurier, C. <strong>Substitution of cysteine for phenylalanine 751 in mature von Willebrand factor is a novel candidate mutation in a family with type IIA von Willebrand disease.</strong> Brit. J. Haemat. 83: 94-99, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8435341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8435341</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1993.tb04637.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8435341">Gaucher et al. (1993)</a> found a heterozygous T-to-G transversion resulting in a phe751-to-cys (F751C) substitution in the mature subunit. Type 2A is a variant form of von Willebrand disease characterized by the absence of high molecular weight VWF multimers in plasma. <a href="#28" class="mim-tip-reference" title="Gaucher, C., Hanss, M., Dechavanne, M., Mazurier, C. <strong>Substitution of cysteine for phenylalanine 751 in mature von Willebrand factor is a novel candidate mutation in a family with type IIA von Willebrand disease.</strong> Brit. J. Haemat. 83: 94-99, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8435341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8435341</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1993.tb04637.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8435341">Gaucher et al. (1993)</a> noted that most of the candidate missense mutations potentially responsible for type 2A VWD have been found clustered within a short segment of VWF, lying between gly742 and glu875 of the mature subunit. <a href="#28" class="mim-tip-reference" title="Gaucher, C., Hanss, M., Dechavanne, M., Mazurier, C. <strong>Substitution of cysteine for phenylalanine 751 in mature von Willebrand factor is a novel candidate mutation in a family with type IIA von Willebrand disease.</strong> Brit. J. Haemat. 83: 94-99, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8435341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8435341</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1993.tb04637.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8435341">Gaucher et al. (1993)</a> suggested that the mutation may induce a conformational change of the VWF subunit affecting either its sensitivity to proteolytic cleavage or, more likely, its intracellular transport as suggested by the abnormal multimeric pattern of platelet VWF observed in these patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8435341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0023" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, GLY550ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61754011 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61754011;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=rs61754011" 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=rs61754011" 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=RCV000000332 OR RCV000086570" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000332, RCV000086570" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000332...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a German woman with von Willebrand disease type 2 (<a href="/entry/613554">613554</a>), referred to as type IIC, <a href="#89" class="mim-tip-reference" title="Schneppenheim, R., Thomas, K. B., Krey, S., Budde, U., Jessat, U., Sutor, A. H., Zieger, B. <strong>Identification of a candidate missense mutation in a family with von Willebrand disease type IIC.</strong> Hum. Genet. 95: 681-686, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789955</a>] [<a href="https://doi.org/10.1007/BF00209487" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7789955">Schneppenheim et al. (1995)</a> identified a homozygous 1898G-A transition in exon 14 of the VWF gene, resulting in a gly550-to-arg (G550R) substitution in the D2 domain. The proband had frequent epistaxis, easy bruising, and menorrhagia, and laboratory studies showed decreased VWF activity and decreased levels of high molecular weight multimers. The subtype of VWD was originally referred to as 'type IIC,' which shows recessive inheritance and an altered multimer pattern. Further family members were heterozygous for the mutation and were phenotypically normal or only mildly affected, in accordance with the recessive pattern of inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7789955" 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="#83" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al. (2006)</a> stated that the subtype previously known as VWD IIC is due to mutations in the VWF propeptide that prevent multimerization of VWF in the Golgi apparatus. This form is now referred to as VWD type 2A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16889557" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0024" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, CYS2773ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61751310 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61751310;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=rs61751310" 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=rs61751310" 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=RCV000000333 OR RCV000086917" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000333, RCV000086917" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000333...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated CYS2010ARG is now designated CYS2773ARG (C2773R). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" 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 VWD type 2 (<a href="/entry/613554">613554</a>), <a href="#86" class="mim-tip-reference" title="Schneppenheim, R., Brassard, J., Krey, S., Budde, U., Kunicki, T. J., Holmberg, L., Ware, J., Ruggeri, Z. M. <strong>Defective dimerization of von Willebrand factor subunits due to a cys-to-arg mutation in type IID von Willebrand disease.</strong> Proc. Nat. Acad. Sci. 93: 3581-3586, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8622978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8622978</a>] [<a href="https://doi.org/10.1073/pnas.93.8.3581" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8622978">Schneppenheim et al. (1996)</a> identified a heterozygous cys2010-to-arg (C2010R) mutation in the mature VWF protein. Recombinant expression of mutant VWF fragments demonstrated that the mutation was responsible for defective disulfide bonding of the C-terminal domains, thus impairing dimer formation. In 1 family, both alleles were normal in the parents and 1 sister; thus, the mutation originated de novo in the proposita. The phenotype of what was then called type IID von Willebrand disease includes autosomal dominant inheritance of a moderate to severe hemorrhagic diathesis, prolonged bleeding time, normal factor VIII procoagulant and VWF antigen levels, but markedly reduced ristocetin cofactor activity due to the lack of large VWF multimers in plasma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8622978" 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="#83" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al. (2006)</a> stated that the subtype previously known as VWD IID is due to heterozygous mutations in the C-terminal domain of VWF that prevent VWF dimerization in the endoplasmic reticulum. This form is now referred to as VWD type 2A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16889557" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<a id="0025" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 MOVED TO <a href="/entry/613160#0006">613160.0006</a></strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0026" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, 6-BP INS, NT1212
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61754006 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61754006;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=rs61754006" 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=rs61754006" 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=RCV000086561 OR RCV002271405" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000086561, RCV002271405" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000086561...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#42" class="mim-tip-reference" title="Holmberg, L., Karpman, D., Isaksson, C., Kristoffersson, A. C., Lethagen, S., Schneppenheim, R. <strong>Ins405-asn-pro mutation in the von Willebrand factor propeptide in recessive type 2A (IIC) von Willebrand's disease.</strong> Thromb. Haemost. 79: 718-722, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9569179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9569179</a>]" pmid="9569179">Holmberg et al. (1998)</a> found that a patient with type 2 VWD (<a href="/entry/613554">613554</a>) reported by <a href="#78" class="mim-tip-reference" title="Ruggeri, Z. M., Nilsson, I. M., Lombardi, R., Holmberg, L., Zimmerman, T. S. <strong>Aberrant multimeric structure of von Willebrand factor in a new variant of von Willebrand's disease (type IIC).</strong> J. Clin. Invest. 70: 1124-1127, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6982283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6982283</a>] [<a href="https://doi.org/10.1172/jci110700" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6982283">Ruggeri et al. (1982)</a> was compound heterozygous for 2 mutations in the VWF gene: a null mutation and a 6-nucleotide insertion, 1212ins6 (AATCCC), in exon 11, predicting the insertion of the amino acids asparagine and proline between phenylalanine-404 and threonine-405 of the von Willebrand propeptide. The patient was originally classified as type IIC, since laboratory studies showed absence of the high molecular weight multimers and a marked increase of the smallest multimer (the protomer) in both plasma and platelets. The IIC phenotype showed recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9569179+6982283" 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="#83" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al. (2006)</a> stated that the subtype previously known as VWD IIC is due to mutations in the VWF propeptide that prevent multimerization of VWF in the Golgi apparatus. This form is now referred to as VWD type 2A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16889557" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0027" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 VON WILLEBRAND DISEASE, TYPE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
VON WILLEBRAND FACTOR VICENZA
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, ARG1205HIS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121964895 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121964895;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=rs121964895" 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=rs121964895" 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=RCV000000335 OR RCV000000336 OR RCV000086666 OR RCV000851598 OR RCV001003906 OR RCV004547447" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000335, RCV000000336, RCV000086666, RCV000851598, RCV001003906, RCV004547447" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000335...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>The arg1205-to-his mutation (R1205H) in the VWF gene is sometimes referred to as VWF Vicenza.</p><p>In affected members of 7 Italian families and in 1 German patient with von Willebrand disease (<a href="/entry/193400">193400</a>) 'Vicenza,' <a href="#87" class="mim-tip-reference" title="Schneppenheim, R., Federici, A. B., Budde, U., Castaman, G., Drewke, E., Krey, S., Mannucci, P. M., Riesen, G., Rodeghiero, F., Zieger, B., Zimmermann, R. <strong>Von Willebrand disease type 2M 'Vicenza' in Italian and German patients: identification of the first candidate mutation (G3864A; R1205H) in 8 families.</strong> Thromb. Haemost. 83: 136-140, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10669167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10669167</a>]" pmid="10669167">Schneppenheim et al. (2000)</a> identified a heterozygous 3864G-A transition in exon 27 of the VWF gene, resulting in an R1205H substitution in the D3 domain. The mutation was not found in unaffected family members or in 100 control chromosomes. Haplotype identity, with minor deviations in 1 Italian family, suggested a common but not very recent genetic origin of R1205H. Von Willebrand disease 'Vicenza' was originally described in patients living in the region of Vicenza in Italy (<a href="#56" class="mim-tip-reference" title="Mannucci, P. M., Lombardi, R., Castaman, G., Dent, J. A., Lattuada, A., Rodeghiero, F., Zimmerman, T. S. <strong>Von Willebrand disease 'Vicenza' with larger-than-normal (supranormal) von Willebrand factor multimers.</strong> Blood 71: 65-70, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3257148/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3257148</a>]" pmid="3257148">Mannucci et al., 1988</a>). <a href="#74" class="mim-tip-reference" title="Randi, A. M., Sacchi, E., Castaman, G. C., Rodeghiero, F., Mannucci, P. M. <strong>The genetic defect of type I von Willebrand disease 'Vicenza' is linked to the von Willebrand factor gene.</strong> Thromb. Haemost. 69: 173-176, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8456430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8456430</a>]" pmid="8456430">Randi et al. (1993)</a> demonstrated that the clinical disorder in Italian patients is linked to the VWF gene. A number of additional families were identified in Germany by <a href="#111" class="mim-tip-reference" title="Zieger, B., Budde, U., Jessat, U., Zimmermann, R., Simon, M., Katzel, R., Sutor, A. H. <strong>New families with von Willebrand disease type 2M (Vicenza).</strong> Thromb. Res. 87: 57-64, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9253800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9253800</a>] [<a href="https://doi.org/10.1016/s0049-3848(97)00104-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9253800">Zieger et al. (1997)</a>. The phenotype was characterized by these groups as showing autosomal dominant inheritance and low levels of VWF antigen in the presence of high molecular weight and ultra high molecular weight multimers, so-called 'supranormal' multimers, similar to those seen in normal plasma after infusion of desmopressin. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8456430+3257148+10669167+9253800" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Casonato, A., Pontara, E., Sartorello, F., Cattini, M. G., Sartori, M. T., Padrini, R., Girolami, A. <strong>Reduced von Willebrand factor survival in type Vicenza von Willebrand disease.</strong> Blood 99: 180-184, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11756169/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11756169</a>] [<a href="https://doi.org/10.1182/blood.v99.1.180" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11756169">Casonato et al. (2002)</a> identified 4 additional families with the R1205H variant. Affected individuals showed a mild bleeding tendency and significant decrease in plasma VWF antigen and ristocetin cofactor activity, but normal platelet VWF levels. Larger than normal VWF multimers were also observed. However, VWF multimers disappeared rapidly from the circulation after desmopressin, indicating reduced survival of the mutant VWF protein. Since ristocetin-induced platelet aggregation was normal, <a href="#11" class="mim-tip-reference" title="Casonato, A., Pontara, E., Sartorello, F., Cattini, M. G., Sartori, M. T., Padrini, R., Girolami, A. <strong>Reduced von Willebrand factor survival in type Vicenza von Willebrand disease.</strong> Blood 99: 180-184, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11756169/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11756169</a>] [<a href="https://doi.org/10.1182/blood.v99.1.180" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11756169">Casonato et al. (2002)</a> attributed the phenotype to reduced survival of normally synthesized VWF, which is consistent with type 1 VWF. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11756169" 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 Wales, <a href="#51" class="mim-tip-reference" title="Lester, W. A., Guilliatt, A. M., Surdhar, G. K., Enayat, S. M., Wilde, J. T., Willoughby, S., Grundy, P., Cumming, A. M., Collins, P. W., Hill, F. G. H. <strong>Inherited and de novo von Willebrand disease 'Vicenza' in UK families with the R1205H mutation: diagnostic pitfalls and new insights.</strong> Brit. J. Haemat. 135: 91-96, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16925796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16925796</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2006.06251.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16925796">Lester et al. (2006)</a> investigated 7 kindreds with VWD Vicenza R1205H. All affected individuals had been diagnosed with moderate to severe type 1 VWD. Among all families with highly penetrant type 1 VWD investigated in the center, heterozygosity for the R1205H mutation was found to be the most common underlying defect. A severe laboratory phenotype associated with a bleeding history that was milder than expected was commonly observed. <a href="#51" class="mim-tip-reference" title="Lester, W. A., Guilliatt, A. M., Surdhar, G. K., Enayat, S. M., Wilde, J. T., Willoughby, S., Grundy, P., Cumming, A. M., Collins, P. W., Hill, F. G. H. <strong>Inherited and de novo von Willebrand disease 'Vicenza' in UK families with the R1205H mutation: diagnostic pitfalls and new insights.</strong> Brit. J. Haemat. 135: 91-96, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16925796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16925796</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2006.06251.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16925796">Lester et al. (2006)</a> provided evidence that the R1205H mutation can arise de novo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16925796" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Cumming, A., Grundy, P., Keeney, S., Lester, W., Enayat, S., Guilliatt, A., Bowen, D., Pasi, J., Keeling, D., Hill, F., Bolton-Maggs, P. H., Hay, C., Collins, P. B. <strong>An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease.</strong> Thromb. Haemost. 96: 630-641, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17080221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17080221</a>]" pmid="17080221">Cumming et al. (2006)</a> identified the Vicenza variant in 4 (12.5%) of 32 UK patients with type 1 VWD. These authors stated that the R1205H substitution resulted from a 3614G-A transition in exon 27. The mutation was highly penetrant and consistently associated with moderate to severe type I disease. VWF multimer studies did not show the presence of ultralarge multimers in any affected individuals; the authors thus classified the Vicenza variant to be a type 1 quantitative defect, rather than a type 2M qualitative defect as had been suggested by <a href="#13" class="mim-tip-reference" title="Castaman, G., Rodeghiero, F., Mannucci, P. M. <strong>The elusive pathogenesis of von Willebrand disease Vicenza. (Letter)</strong> Blood 99: 4243-4244, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12043692/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12043692</a>] [<a href="https://doi.org/10.1182/blood.v99.11.4243" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12043692">Castaman et al. (2002)</a>. Three of the 4 families reported by <a href="#16" class="mim-tip-reference" title="Cumming, A., Grundy, P., Keeney, S., Lester, W., Enayat, S., Guilliatt, A., Bowen, D., Pasi, J., Keeling, D., Hill, F., Bolton-Maggs, P. H., Hay, C., Collins, P. B. <strong>An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease.</strong> Thromb. Haemost. 96: 630-641, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17080221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17080221</a>]" pmid="17080221">Cumming et al. (2006)</a> shared the same haplotype, suggesting a common origin of the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17080221+12043692" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a review, <a href="#83" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al. (2006)</a> noted that the Vicenza VWF variant has increased clearance compared to wildtype VWF. <a href="#83" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al. (2006)</a> also noted that the Vicenza variant has been classified as VWD type 2M due to the presence of high molecular weight multimers. However, since VWF antigen and functional activity are decreased proportionately, it is better classified as VWD type 1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16889557" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0028" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 VON WILLEBRAND DISEASE, TYPE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, CYS1149ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61748511 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61748511;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=rs61748511" 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=rs61748511" 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=RCV000000337 OR RCV000086657 OR RCV002264636 OR RCV004821258" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000337, RCV000086657, RCV002264636, RCV004821258" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000337...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#23" class="mim-tip-reference" title="Eikenboom, J. C. J., Matsushita, T., Reitsma, P. H., Tuley, E. A., Castaman, G., Briet, E., Sadler, J. E. <strong>Dominant type 1 von Willebrand disease caused by mutated cysteine residues in the D3 domain of von Willebrand factor.</strong> Blood 88: 2433-2441, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8839833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8839833</a>]" pmid="8839833">Eikenboom et al. (1996)</a> described a family in the Netherlands in which 3 affected members with type 1 von Willebrand disease (<a href="/entry/193400">193400</a>) and VWF levels 10 to 15% of normal were heterozygous for a mutation in exon 26 of the VWF gene, resulting in a cys1149-to-arg (C1149R) substitution in the D3 domain (numbered from the initiation codon, or cys386-to-arg, numbered from the N terminus of the mature subunit). The mutation resulted in a decrease in the secretion of coexpressed normal VWF, and the mutation was proposed to cause intracellular retention of pro-VWF heterodimers. The multimer pattern remained nearly normal and consistent with a dominant VWD type 1 phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8839833" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Bodo, I., Katsumi, A., Tuley, E. A., Eikenboom, J. C. J., Dong, Z., Sadler, J. E. <strong>Type 1 von Willebrand disease mutation cys1149-to-arg causes intracellular retention and degradation of heterodimers: a possible general mechanism for dominant mutations of oligomeric proteins.</strong> Blood 98: 2973-2979, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11698279/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11698279</a>] [<a href="https://doi.org/10.1182/blood.v98.10.2973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11698279">Bodo et al. (2001)</a> performed experiments supporting the hypothesis that normal and C1149R mutant subunits formed heterodimers that, like homodimers of C1149R, were retained in the endoplasmic reticulum. Such a mechanism would explain the dominant-negative effect of the C1149R mutation on VWF secretion, and the authors suggested that a similar dominant-negative mechanism could cause quantitative deficiencies of other multisubunit proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11698279" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0029" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 VON WILLEBRAND DISEASE, TYPE 1, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, TYR1584CYS
|
|
</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> rs1800386 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1800386;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/rs1800386?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=rs1800386" 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=rs1800386" 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=RCV000000338 OR RCV000086795 OR RCV000622977 OR RCV000678772 OR RCV001255177 OR RCV001843449 OR RCV002280857 OR RCV003313770 OR RCV004547448 OR RCV004700174 OR RCV004795364" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000338, RCV000086795, RCV000622977, RCV000678772, RCV001255177, RCV001843449, RCV002280857, RCV003313770, RCV004547448, RCV004700174, RCV004795364" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000338...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#68" class="mim-tip-reference" title="O'Brien, L. A., James, P. D., Othman, M., Berber, E., Cameron, C., Notley, C. R. P., Hegadorn, C. A., Sutherland, J. J., Hough, C., Rivard, G. E., O'Shaunessey, D., Association of Hemophilia Clinic Directors of Canada, Lillicrap, D. <strong>Founder von Willebrand factor haplotype associated with type I von Willebrand disease.</strong> Blood 102: 549-557, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12649144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12649144</a>] [<a href="https://doi.org/10.1182/blood-2002-12-3693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12649144">O'Brien et al. (2003)</a> addressed the molecular basis of type 1 von Willebrand disease (<a href="/entry/193400">193400</a>) in a comprehensive manner through a Canadian population-based study. In 10 Canadian families and 2 families from the UK with type 1 VWD, <a href="#68" class="mim-tip-reference" title="O'Brien, L. A., James, P. D., Othman, M., Berber, E., Cameron, C., Notley, C. R. P., Hegadorn, C. A., Sutherland, J. J., Hough, C., Rivard, G. E., O'Shaunessey, D., Association of Hemophilia Clinic Directors of Canada, Lillicrap, D. <strong>Founder von Willebrand factor haplotype associated with type I von Willebrand disease.</strong> Blood 102: 549-557, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12649144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12649144</a>] [<a href="https://doi.org/10.1182/blood-2002-12-3693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12649144">O'Brien et al. (2003)</a> identified a heterozygous 4751A-G transition in exon 28 of the VWF gene, resulting in a tyr1584-to-cys (Y1584C) substitution. The Y1584C variant was found in 1 of 100 controls, but this individual had low VWF antigen levels, suggesting an affected status. One study participant with the mutation had a normal VWF antigen level and no history of bleeding, suggesting incomplete penetrance, and another who was homozygous for the mutation had significantly decreased VWF antigen levels. The mutation was associated with a common haplotype in a significant portion of patients with the disorder and was in-phase with a splice site variation (5312-19A-C) in some families. In vitro functional expression studies showed that the mutation resulted in increased intracellular retention of the VWF protein, resulting in a quantitative defect. Molecular dynamic simulation on a homology model of the VWF-A2 domain containing the Y1584C mutation showed that no significant structural changes occurred as a result of the substitution, but that a new solvent-exposed reactive thiol group was apparent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12649144" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Bowen, D. J., Collins, P. W. <strong>An amino acid polymorphism in von Willebrand factor correlates with increased susceptibility to proteolysis by ADAMTS13.</strong> Blood 103: 941-947, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14525793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14525793</a>] [<a href="https://doi.org/10.1182/blood-2003-05-1505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14525793">Bowen and Collins (2004)</a> described a patient with type 1 von Willebrand disease in whom the von Willebrand factor showed increased susceptibility to proteolysis by ADAMTS13 (<a href="/entry/604134">604134</a>). Investigation of additional family members indicated that increased susceptibility was heritable, but it did not track uniquely with type 1 VWD. Sequence analysis showed that increased susceptibility to proteolysis tracked with the Y1584C substitution. A prospective study of 200 individuals yielded 2 Y1584C heterozygotes; for both, plasma VWF showed increased susceptibility to proteolysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14525793" 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="Bowen, D. J., Collins, P. W., Lester, W., Cumming, A. M., Keeney, S., Grundy, P., Enayat, S. M., Bolton-Maggs, P. H. B., Keeling, D. M., Khair, K., Tait, R. C., Wilde, J. T., Pasi, K. J., Hill, F. G. <strong>The prevalence of the cysteine 1584 variant of von Willebrand factor is increased in type 1 von Willebrand disease: co-segregation with increased susceptibility to ADAMTS13 proteolysis but not clinical phenotype.</strong> Brit. J. Haemat. 128: 830-836, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15755288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15755288</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2005.05375.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15755288">Bowen et al. (2005)</a> identified heterozygosity for the Y1584C variant in 19 (25%) of 76 UK patients with type 1 VWD. This corresponded to 8 (27%) of 30 total families studied. However, the Y1584C variant did not segregate with disease in 4 families: 5 unaffected individuals carried the variant, whereas 3 affected individuals did not. These findings indicated that Y1584C is not solely causative of type 1 VWD. Eighteen of the 19 patients were ABO blood group (<a href="/entry/616093">616093</a>) type O, suggesting there may be an interaction between C1584 and blood group O. In vitro studies of plasma showed that Y1584C VWF had increased susceptibility to proteolysis by ADAMTS13, even in those who did not have VWD. <a href="#8" class="mim-tip-reference" title="Bowen, D. J., Collins, P. W., Lester, W., Cumming, A. M., Keeney, S., Grundy, P., Enayat, S. M., Bolton-Maggs, P. H. B., Keeling, D. M., Khair, K., Tait, R. C., Wilde, J. T., Pasi, K. J., Hill, F. G. <strong>The prevalence of the cysteine 1584 variant of von Willebrand factor is increased in type 1 von Willebrand disease: co-segregation with increased susceptibility to ADAMTS13 proteolysis but not clinical phenotype.</strong> Brit. J. Haemat. 128: 830-836, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15755288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15755288</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2005.05375.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15755288">Bowen et al. (2005)</a> proposed a mechanism in which Y1584C VWF undergoes increased proteolysis, which may increase bleeding risk in carriers. However, presence for the variant is not causative for the disorder, and may instead represent a risk factor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15755288" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Cumming, A., Grundy, P., Keeney, S., Lester, W., Enayat, S., Guilliatt, A., Bowen, D., Pasi, J., Keeling, D., Hill, F., Bolton-Maggs, P. H., Hay, C., Collins, P. B. <strong>An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease.</strong> Thromb. Haemost. 96: 630-641, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17080221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17080221</a>]" pmid="17080221">Cumming et al. (2006)</a> identified heterozygosity for the Y1584C variant in 8 (25%) of 32 UK families and in 19 (17%) of 119 related individuals with type 1 VWD. Eighteen (95%) of the 19 individuals were blood group O. Heterozygosity for Y1584C segregated with VWD in 3 families, did not segregate with VWD in 4 families, and showed equivocal results in 2 families. <a href="#16" class="mim-tip-reference" title="Cumming, A., Grundy, P., Keeney, S., Lester, W., Enayat, S., Guilliatt, A., Bowen, D., Pasi, J., Keeling, D., Hill, F., Bolton-Maggs, P. H., Hay, C., Collins, P. B. <strong>An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease.</strong> Thromb. Haemost. 96: 630-641, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17080221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17080221</a>]" pmid="17080221">Cumming et al. (2006)</a> concluded that Y1594C is a polymorphism that is frequently associated with type 1 VWD, but shows incomplete penetrance and does not consistently segregate with the disease. The association with blood group type O may be related to the fact that both blood group O and Y1584C are associated with increased proteolysis of VWF by ADAMTS13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17080221" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0030" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 VON WILLEBRAND DISEASE, TYPE 2M</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, SER1285PHE
|
|
</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> rs61749380 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61749380;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/rs61749380?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=rs61749380" 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=rs61749380" 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=RCV000000339 OR RCV000086691" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000339, RCV000086691" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000339...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a French mother and son with VWD type 2M (see <a href="/entry/613554">613554</a>), <a href="#92" class="mim-tip-reference" title="Stepanian, A., Ribba, A.-S., Lavergne, J.-M., Fressinaud, E., Juhan-Vague, I., Mazurier, C., Girma, J.-P., Meyer, D. <strong>A new mutation, S1285F, within the A1 loop of von Willebrand factor induces a conformational change in A1 loop with abnormal binding to platelet GPIb and botrocetin causing type 2M von Willebrand disease.</strong> Brit. J. Haemat. 120: 643-651, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12588351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12588351</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2003.04168.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12588351">Stepanian et al. (2003)</a> identified a heterozygous 3854C-T transition in exon 28 of the VWF gene, resulting in a ser1285-to-phe (S1285F) substitution in the A1 loop of the protein. In vitro functional expression studies in COS-7 cells showed that the mutant VWF had markedly reduced ristocetin-induced binding to platelets via GP1BA (<a href="/entry/606672">606672</a>), consistent with a loss of function. The findings indicated that the S1285F mutation altered the folding of the A1 loop and prevented the correct exposure of VWF binding sites to GP1BA. Both patients had a moderate bleeding syndrome with epistaxis and easy bruising. Laboratory studies showed mildly decreased VWF antigen levels, normal multimers, and severely decreased VWF functional activity. Factor VIII (F8; <a href="/entry/300841">300841</a>) was mildly decreased and platelet counts were normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12588351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0031" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 VON WILLEBRAND DISEASE, TYPE 2N</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, TYR795CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61748478 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61748478;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=rs61748478" 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=rs61748478" 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=RCV000000340 OR RCV000086607" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000340, RCV000086607" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000340...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a French patient with VWD type 2N (see <a href="/entry/613554">613554</a>), <a href="#39" class="mim-tip-reference" title="Hilbert, L., Jorieux, S., Fontenay-Roupie, M., Guicheteau, M., Fressinaud, E., Meyer, D., Mazurier, C., the INSERM Network on Molecular Abnormalities in von Willebrand Disease. <strong>Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene.</strong> Brit. J. Haemat. 127: 184-189, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15461624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15461624</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2004.05187.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15461624">Hilbert et al. (2004)</a> identified compound heterozygosity for 2 mutations in the VWF gene: a 2384A-G transition in exon 18 resulting in a tyr795-to-cys (Y795C) substitution in the D-prime domain, and R854Q (<a href="#0013">613160.0013</a>). In vitro functional expression assays showed that the mutant VWF protein had decreased binding to factor VIII (<a href="/entry/300841">300841</a>), and resulted in an abnormal multimeric pattern consistent with ultralarge multimers. <a href="#39" class="mim-tip-reference" title="Hilbert, L., Jorieux, S., Fontenay-Roupie, M., Guicheteau, M., Fressinaud, E., Meyer, D., Mazurier, C., the INSERM Network on Molecular Abnormalities in von Willebrand Disease. <strong>Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene.</strong> Brit. J. Haemat. 127: 184-189, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15461624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15461624</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2004.05187.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15461624">Hilbert et al. (2004)</a> suggested that the effect on the cysteine residue may alter protein conformation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15461624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0032" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0032 VON WILLEBRAND DISEASE, TYPE 2N</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, CYS804PHE
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs62643630 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs62643630;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=rs62643630" 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=rs62643630" 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=RCV000000341 OR RCV000086609" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000341, RCV000086609" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000341...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a French patient with VWD type 2N (see <a href="/entry/613554">613554</a>), <a href="#39" class="mim-tip-reference" title="Hilbert, L., Jorieux, S., Fontenay-Roupie, M., Guicheteau, M., Fressinaud, E., Meyer, D., Mazurier, C., the INSERM Network on Molecular Abnormalities in von Willebrand Disease. <strong>Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene.</strong> Brit. J. Haemat. 127: 184-189, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15461624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15461624</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2004.05187.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15461624">Hilbert et al. (2004)</a> identified compound heterozygosity for 2 mutations in the VWF gene: a 2411G-T transversion in exon 18 resulting in a cys804-to-phe (C804F) substitution in the D-prime domain, and R854Q (<a href="#0013">613160.0013</a>). In vitro functional expression assays showed that the mutant VWF protein had decreased binding to factor VIII (<a href="/entry/300841">300841</a>), and resulted in an abnormal multimeric pattern consistent with loss of ultralarge multimers. <a href="#39" class="mim-tip-reference" title="Hilbert, L., Jorieux, S., Fontenay-Roupie, M., Guicheteau, M., Fressinaud, E., Meyer, D., Mazurier, C., the INSERM Network on Molecular Abnormalities in von Willebrand Disease. <strong>Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene.</strong> Brit. J. Haemat. 127: 184-189, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15461624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15461624</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2004.05187.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15461624">Hilbert et al. (2004)</a> suggested that the effect on the cysteine residue may alter protein conformation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15461624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0033" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0033 VON WILLEBRAND DISEASE, TYPE 2B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WVF, PRO1266LEU
|
|
</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> rs61749370 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61749370;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/rs61749370?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=rs61749370" 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=rs61749370" 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=RCV000000342 OR RCV000086676 OR RCV000314989 OR RCV000853236 OR RCV002247228 OR RCV003313771 OR RCV004547449" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000342, RCV000086676, RCV000314989, RCV000853236, RCV002247228, RCV003313771, RCV004547449" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000342...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Goodeve, A. C. <strong>The genetic basis of von Willebrand disease.</strong> Blood Rev. 24: 123-134, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>] [<a href="https://doi.org/10.1016/j.blre.2010.03.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20409624">Goodeve (2010)</a> noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated PRO503LEU is now designated PRO1266LEU (P1266L). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a Swedish family (<a href="#40" class="mim-tip-reference" title="Holmberg, L., Berntorp, E., Donner, M., Nilsson, I. M. <strong>von Willebrand's disease characterised by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers.</strong> Blood 68: 668-672, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3488775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3488775</a>]" pmid="3488775">Holmberg et al., 1986</a>) and a German family with a variant of VWD type 2B (see <a href="/entry/613554">613554</a>), <a href="#41" class="mim-tip-reference" title="Holmberg, L., Dent, J. A., Schneppenheim, R., Budde, U., Ware, J., Ruggeri, Z. M. <strong>von Willebrand factor mutation enhancing interaction with platelets in patients with normal multimeric structure.</strong> J. Clin. Invest. 91: 2169-2177, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8486782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8486782</a>] [<a href="https://doi.org/10.1172/JCI116443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8486782">Holmberg et al. (1993)</a> identified a heterozygous C-to-T transition in the VWF gene, resulting in a pro503-to-leu (P503L) substitution in the mature subunit. The phenotype was unique in that there was a mild bleeding disorder, and laboratory studies showed that platelets aggregated at much lower ristocetin concentrations than normal. The bleeding time was variously prolonged, and VWF:Ag, VWF activity, and F8 were decreased. All VWF multimers were present, and there was no thrombocytopenia. The defect in this family, inherited as an autosomal dominant trait, resembled that of type 2B because of the response to ristocetin, but differed because all VWF multimers were present. <a href="#40" class="mim-tip-reference" title="Holmberg, L., Berntorp, E., Donner, M., Nilsson, I. M. <strong>von Willebrand's disease characterised by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers.</strong> Blood 68: 668-672, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3488775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3488775</a>]" pmid="3488775">Holmberg et al. (1986)</a> referred to it as 'type 2 Malmo.' <a href="#102" class="mim-tip-reference" title="Weiss, J. G., Sussman, I. I. <strong>Increased ristocetin-induced platelet aggregation (RIPA) and plasma von Willebrand factor (VWF) containing all VWF multimers (type I--New York). (Abstract)</strong> Blood 66 (suppl. 1): 329, 1985."None>Weiss and Sussman (1985)</a> reported a similarly affected family, and referred to this variant as 'type I New York' (<a href="#83" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al., 2006</a>). <a href="#105" class="mim-tip-reference" title="Wylie, B., Gibson, J., Uhr, E., Kronenberg, H. <strong>Von Willebrand's disease characterized by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers in plasma: a new subtype.</strong> Pathology 20: 62-63, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3259690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3259690</a>] [<a href="https://doi.org/10.3109/00313028809085199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3259690">Wylie et al. (1988)</a> also described this variant and noted that there was no spontaneous aggregation of platelets. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16889557+3259690+3488775+8486782" 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="#83" class="mim-tip-reference" title="Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others. <strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong> J. Thromb. Haemost. 4: 2103-2114, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>] [<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16889557">Sadler et al. (2006)</a> emphasized that this variant is a form of VWD type 2B with increased sensitivity to ristocetin in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16889557" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0034" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0034 VON WILLEBRAND DISEASE, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, CYS2362PHE
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61750630 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61750630;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=rs61750630" 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=rs61750630" 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=RCV000000343 OR RCV000086870" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000343, RCV000086870" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000343...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In several patients from northern Italy with VWD type 3 (<a href="/entry/277480">277480</a>), <a href="#22" class="mim-tip-reference" title="Eikenboom, J. C. J., Castaman, G., Vos, H. L., Bertina, R. M., Rodeghiero, F. <strong>Characterization of the genetic defects in recessive type 1 and type 3 von Willebrand disease patients of Italian origin.</strong> Thromb. Haemost. 79: 709-717, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9569178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9569178</a>]" pmid="9569178">Eikenboom et al. (1998)</a> identified a homozygous mutation in the VWF gene, resulting in a cys2362-to-phe (C2362F) substitution. Haplotype analysis indicated a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9569178" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#95" class="mim-tip-reference" title="Tjernberg, P., Castaman, G., Vos, H. L., Bertina, R. M., Eikenboom, J. C. <strong>Homozygous C2362F von Willebrand factor induces intracellular retention of mutant von Willebrand factor resulting in autosomal recessive severe von Willebrand disease.</strong> Brit. J. Haemat. 133: 409-418, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16643449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16643449</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2006.06055.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16643449">Tjernberg et al. (2006)</a> demonstrated that recombinant C2362F expressed in 293T human kidney cells resulted in significantly decreased expression of the mutant protein (8% of controls), although there was similar production. The findings indicated increased intracellular retention of the mutant protein. The mutant protein produced showed less of the multimeric structure, suggesting that the loss of a cysteine on an interchain bond impaired normal multimerization, since there was no difference in subunit size from the wildtype. There was also no evidence of a dominant-negative effect, suggesting that the ultimate effects of the C2362F mutation were similar to that of a null allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16643449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0035" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0035 VON WILLEBRAND DISEASE, TYPE 2N</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, TYR357TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61754002 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61754002;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=rs61754002" 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=rs61754002" 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=RCV000000344 OR RCV000086555" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000344, RCV000086555" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000344...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 20-year-old French woman with VWD type 2N (see <a href="/entry/613554">613554</a>), <a href="#59" class="mim-tip-reference" title="Mazurier, C., Parquet-Gernez, A., Gaucher, C., Lavergne, J.-M., Goudemand, J. <strong>Factor VIII deficiency not induced by FVIII gene mutation in a female first cousin of two brothers with haemophilia A.</strong> Brit. J. Haemat. 119: 390-392, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12406074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12406074</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2002.03819.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12406074">Mazurier et al. (2002)</a> identified compound heterozygosity for 2 mutations in the VWF gene: a 1071C-A transversion in exon 9, resulting in a tyr357-to-ter (Y357X) substitution, and a 3178T-C transition in exon 24, resulting in a cys1060-to-arg (C1060R; <a href="#0036">613160.0036</a>) substitution. The authors noted that the Y357X mutation is a type 3 mutation (<a href="/entry/277480">277480</a>) presumably because it represents a truncating mutation and lack of protein expression. The patient had very low levels of VWF and F8, and absent binding of VWF to F8. She had epistaxis, hematomas, and hematemesis throughout childhood. The diagnosis was complicated at first because 2 male first cousins had F8 deficiency (<a href="/entry/306700">306700</a>) due to a hemizygous mutation in the F8 gene (C179G; <a href="/entry/300841#0268">300841.0268</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12406074" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0036" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0036 VON WILLEBRAND DISEASE, TYPE 2N</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, CYS1060ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs61748497 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61748497;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=rs61748497" 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=rs61748497" 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=RCV000000345 OR RCV000086640" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000345, RCV000086640" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000345...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See <a href="#0035">613160.0035</a> and <a href="#59" class="mim-tip-reference" title="Mazurier, C., Parquet-Gernez, A., Gaucher, C., Lavergne, J.-M., Goudemand, J. <strong>Factor VIII deficiency not induced by FVIII gene mutation in a female first cousin of two brothers with haemophilia A.</strong> Brit. J. Haemat. 119: 390-392, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12406074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12406074</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2002.03819.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12406074">Mazurier et al. (2002)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12406074" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0037" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0037 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, ASN528SER
|
|
</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> rs61754010 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61754010;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/rs61754010?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=rs61754010" 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=rs61754010" 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=RCV000000346 OR RCV000086569 OR RCV002243608" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000346, RCV000086569, RCV002243608" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000346...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 Turkish boys, born of consanguineous parents, with VWD type 2A (see <a href="/entry/613554">613554</a>), <a href="#37" class="mim-tip-reference" title="Haberichter, S. L., Budde, U., Obser, T., Schneppenheim, S., Wermes, C., Schneppenheim, R. <strong>The mutation N528S in the von Willebrand factor (VWF) propeptide causes defective multimerization and storage of VWF.</strong> Blood 115: 4580-4587, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20335223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20335223</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20335223[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/10.1182/blood-2009-09-244327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20335223">Haberichter et al. (2010)</a> identified a homozygous 1583A-G transition in exon 14 of the VWF gene, resulting in an asn528-to-ser (N528S) substitution in the D2 domain of the propeptide. The phenotype was characterized by significant mucocutaneous bleeding beginning in childhood; 1 patient had joint bleeding. The patients had decreased plasma and platelet VWF antigen and decreased platelet VWF binding to collagen, with only slightly reduced F8 activity. There was a poor VWF response to desmopressin infusion, indicating lack of VWF storage in endothelial cells. The VWF multimer pattern lacked both high molecular weight multimers and medium-sized multimers particularly severe in platelets, consistent with VWD type 2A and the historical subclassification of type IIC. In vitro functional expression studies in mammalian cells showed that the N528S mutation introduced into a full-length VWF expression vector resulted in decreased VWF secretion (7.5% of controls) with an abnormal multimer pattern lacking both high molecular weight and medium-sized multimers, and lack of proper trafficking to storage granules. Detailed studies using coexpression of the mutant and wildtype propeptide with mutant and wildtype full-length VWF indicated a defective interaction of VWF with its intracellular propeptide chaperone, resulting in loss of regulated storage of VWF. Heterozygous expression of the mutant and wildtype alleles resulted in normal VWF secretion and multimerization, confirming the recessive nature of this mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20335223" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0038" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0038 VON WILLEBRAND DISEASE, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
VON WILLEBRAND DISEASE, TYPE 1, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, 8.6-KB DEL, EX4-5
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000144413 OR RCV002271339 OR RCV002271340" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000144413, RCV002271339, RCV002271340" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000144413...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 Caucasian British patients, including 2 sibs, with VWD type 3 (<a href="/entry/277480">277480</a>), <a href="#93" class="mim-tip-reference" title="Sutherland, M. S., Cumming, A. M., Bowman, M., Bolton-Maggs, P. H. B., Bowen, D. J., Collins, P. W., Hay, C. R. M., Will, A. M., Keeney, S. <strong>A novel deletion mutation is recurrent in von Willebrand disease types 1 and 3.</strong> Blood 114: 1091-1098, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19372260/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19372260</a>] [<a href="https://doi.org/10.1182/blood-2008-08-173278" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19372260">Sutherland et al. (2009)</a> identified a homozygous 8,631-bp deletion in the VWF gene, resulting in an in-frame deletion of exons 4 and 5. The deletion spanned from within intron 3 to within intron 5, and the breakpoints occurred in inverted AluY repeat elements. Analysis of other patients with VWD type 3 showed that 4 were compound heterozygous for the exon 4-5 deletion and another pathogenic mutation, and 1 was heterozygous for the deletion but with no second mutation detected. In total, 7 of 12 white patients with VWD type 3 carried this deletion, which was not found in 9 patients of Asian origin. Haplotype analysis confirmed a founder effect in the white British population. Heterozygosity for this deletion was found in 2 of 34 probands with VWD type 1 (<a href="/entry/193400">193400</a>), their affected family members, and 1 unaffected family member, indicating reduced penetrance. An unrelated patient with VWD type 1 was also found to carry a heterozygous deletion. In vitro functional expression studies showed that the deletion resulted in significantly decreased protein secretion, with a 98% decrease in the homozygous state and an 86% decrease in the heterozygous state, consistent with a dominant-negative effect. Expression of the homozygous mutation, but not of the heterozygous mutation, resulted in defective multimer production. The mutation was not found in 200 control alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19372260" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0039" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0039 VON WILLEBRAND DISEASE, TYPE 2A/IIE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, TYR1146CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267607326 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607326;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=rs267607326" 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=rs267607326" 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=RCV000024001 OR RCV000086656 OR RCV000851956 OR RCV001800314 OR RCV002264640 OR RCV004821262" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000024001, RCV000086656, RCV000851956, RCV001800314, RCV002264640, RCV004821262" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000024001...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 12 (32%) of 38 probands with von Willebrand disease type 2A/IIE (see <a href="/entry/613554">613554</a>), <a href="#88" class="mim-tip-reference" title="Schneppenheim, R., Michiels, J. J., Obser, T., Oyen, F., Pieconka, A., Schneppenheim, S., Will, K., Zieger, B., Budde, U. <strong>A cluster of mutations in the D3 domain of von Willebrand factor correlates with a distinct subgroup of von Willebrand disease: type 2A/IIE.</strong> Blood 115: 4894-4901, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20351307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20351307</a>] [<a href="https://doi.org/10.1182/blood-2009-07-226324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20351307">Schneppenheim et al. (2010)</a> identified a heterozygous 3437A-C transversion in exon 26 of the VWF gene, resulting in a tyr1146-to-cys (Y1146C) substitution in the D3 domain. Plasma from patients showed complete absence of large VWF multimers, and in vitro expression studies indicated that the Y1146C-mutant protein caused a severe reduction in or lack of high molecular weight monomers. and decreased secreted VWF antigen levels. However, clinical symptoms were heterogeneous among carriers, ranging from mild to severe bleeding. <a href="#88" class="mim-tip-reference" title="Schneppenheim, R., Michiels, J. J., Obser, T., Oyen, F., Pieconka, A., Schneppenheim, S., Will, K., Zieger, B., Budde, U. <strong>A cluster of mutations in the D3 domain of von Willebrand factor correlates with a distinct subgroup of von Willebrand disease: type 2A/IIE.</strong> Blood 115: 4894-4901, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20351307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20351307</a>] [<a href="https://doi.org/10.1182/blood-2009-07-226324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20351307">Schneppenheim et al. (2010)</a> suggested several mechanisms acting in concert, including decreased secretion of VWF, the change affecting a cysteine residue which may impact multimerization, and decreased half-life of the mutant protein. Altered ADAMTS13-mediated proteolysis did not appear to be a primary factor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20351307" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0040" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0040 VON WILLEBRAND DISEASE, TYPE 2CB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, TRP1745CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267607352 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607352;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=rs267607352" 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=rs267607352" 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=RCV000086831 OR RCV002271338 OR RCV004821273" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000086831, RCV002271338, RCV004821273" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000086831...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an elderly woman with von Willebrand disease type 2CB (see <a href="/entry/613554">613554</a>), <a href="#76" class="mim-tip-reference" title="Riddell, A. F., Gomez, K., Millar, C. M., Mellars, G., Gill, S., Brown, S. A., Sutherland, M., Laffan, M. A., McKinnon, T. A. <strong>Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor.</strong> Blood 114: 3489-3496, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687512</a>] [<a href="https://doi.org/10.1182/blood-2008-10-184317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19687512">Riddell et al. (2009)</a> identified compound heterozygosity for 2 mutations in the VWF gene: a 5235G-T transversion in exon 30, resulting in a trp1745-to-cys (W1745C) substitution in the A3 domain, and R760H (<a href="#0041">613160.0041</a>). She had a lifelong history of severe bleeding episodes, including epistaxis, ecchymosis, menorrhagia, and bleeding after dental extractions. The proband had 2 offspring, each of whom was heterozygous for 1 of the mutations and showed minor bleeding symptoms not requiring treatment. Both persons with the W1745C mutation had markedly reduced ratios of VWF collagen-binding activity to VWF antigen (CB:Ag) against type III collagen and type I collagen. There were normal values of VWF:RCo to VWF:Ag (RCo:Ag), normal VWF multimer analysis, and normal ristocetin-induced platelet aggregation. Treatment of the mother with DDAVP resulted in a good functional response with a rise in VWF:CB resulting from an overall increase in the amount of circulating VWF, even though the qualitative defect in collagen binding remained. These findings and in vitro expression studies indicated that the W1745C-mutant protein caused a specific defect in collagen binding, which <a href="#76" class="mim-tip-reference" title="Riddell, A. F., Gomez, K., Millar, C. M., Mellars, G., Gill, S., Brown, S. A., Sutherland, M., Laffan, M. A., McKinnon, T. A. <strong>Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor.</strong> Blood 114: 3489-3496, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687512</a>] [<a href="https://doi.org/10.1182/blood-2008-10-184317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19687512">Riddell et al. (2009)</a> suggested represented a novel classification subtype termed 'VWF 2CB.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19687512" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0041" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0041 VON WILLEBRAND DISEASE, TYPE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, ARG760HIS
|
|
</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> rs61748467 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs61748467;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/rs61748467?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=rs61748467" 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=rs61748467" 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=RCV000024003 OR RCV000086595" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000024003, RCV000086595" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000024003...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with a mild bleeding tendency and laboratory studies consistent with VWD type 1 (<a href="/entry/193400">193400</a>), <a href="#76" class="mim-tip-reference" title="Riddell, A. F., Gomez, K., Millar, C. M., Mellars, G., Gill, S., Brown, S. A., Sutherland, M., Laffan, M. A., McKinnon, T. A. <strong>Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor.</strong> Blood 114: 3489-3496, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687512</a>] [<a href="https://doi.org/10.1182/blood-2008-10-184317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19687512">Riddell et al. (2009)</a> identified a heterozygous 2279G-A transition in the VWF gene, resulting in an arg760-to-his (R760H; <a href="#0041">613160.0041</a>) substitution. Laboratory studies showed a concordant reduction in VWF:Ag, VWF:RCo, and VWF:CB, with a normal multimer pattern. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19687512" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0042" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0042 VON WILLEBRAND DISEASE, TYPE 2CB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
VWF, SER1783ALA
|
|
</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> rs267607353 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607353;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/rs267607353?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=rs267607353" 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=rs267607353" 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=RCV000024004 OR RCV000086836 OR RCV002468978" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000024004, RCV000086836, RCV002468978" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000024004...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a mother and son with VWD type 2CB (see <a href="/entry/613554">613554</a>), <a href="#76" class="mim-tip-reference" title="Riddell, A. F., Gomez, K., Millar, C. M., Mellars, G., Gill, S., Brown, S. A., Sutherland, M., Laffan, M. A., McKinnon, T. A. <strong>Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor.</strong> Blood 114: 3489-3496, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687512</a>] [<a href="https://doi.org/10.1182/blood-2008-10-184317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19687512">Riddell et al. (2009)</a> identified a heterozygous 5347T-G transversion in exon 31 of the VWF gene, resulting in a ser1783-to-ala (S1783A) substitution in the A3 domain. Laboratory studies showed normal VWF:Ag, VWF:RCo, and multimers, but decreased binding to both collagen I and collagen III. Defective collagen binding was confirmed by in vitro expression studies. Treatment with DDAVP resulted in a good functional response with a rise in VWF:CB resulting from an overall increase in the amount of circulating VWF, even though the qualitative defect in collagen binding remained. These findings indicated that the S1783A-mutant protein caused a specific defect in collagen binding, which <a href="#76" class="mim-tip-reference" title="Riddell, A. F., Gomez, K., Millar, C. M., Mellars, G., Gill, S., Brown, S. A., Sutherland, M., Laffan, M. A., McKinnon, T. A. <strong>Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor.</strong> Blood 114: 3489-3496, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687512</a>] [<a href="https://doi.org/10.1182/blood-2008-10-184317" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19687512">Riddell et al. (2009)</a> suggested represented a novel classification subtype termed 'VWF 2CB.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19687512" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="seeAlso" class="mim-anchor"></a>
|
|
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<a href="#Bahou1988" class="mim-tip-reference" title="Bahou, W. F., Bowie, E. J. W., Fass, D. N., Ginsburg, D. <strong>Molecular genetic analysis of porcine von Willebrand disease: tight linkage to the von Willebrand factor locus.</strong> Blood 72: 308-313, 1988.">Bahou et al. (1988)</a>; <a href="#Bonthron1986" class="mim-tip-reference" title="Bonthron, D. T., Handin, R. I., Kaufman, R. J., Wasley, L. C., Orr, E. C., Mitsock, L. M., Ewenstein, B., Loscalzo, J., Ginsburg, D., Orkin, S. H. <strong>Structure of pre-pro-von Willebrand factor and its expression in heterologous cells.</strong> Nature 324: 270-273, 1986.">Bonthron et al. (1986)</a>; <a href="#Castaman1999" class="mim-tip-reference" title="Castaman, G., Eikenboom, J. C. J., Bertina, R. M., Rodeghiero, F. <strong>Inconsistency of association between type 1 von Willebrand disease phenotype and genotype in families identified in an epidemiological investigation.</strong> Thromb. Haemost. 82: 1065-1070, 1999.">Castaman et al. (1999)</a>; <a href="#Cumming1992" class="mim-tip-reference" title="Cumming, A. M., Armstrong, J. G., Pendry, K., Burn, A. M., Wensley, R. T. <strong>Polymerase chain reaction amplification of two polymorphic simple repeat sequences within the von Willebrand factor gene: application to family studies in von Willebrand disease.</strong> Hum. Genet. 89: 194-198, 1992.">Cumming et al. (1992)</a>; <a href="#Fay1986" class="mim-tip-reference" title="Fay, P. J., Kawai, Y., Wagner, D. D., Ginsburg, D., Bonthron, D., Ohlsson-Wilhelm, B. M., Chavin, S. I., Abraham, G. N., Handin, R. I., Orkin, S. H., Montgomery, R. R., Marder, V. J. <strong>Propolypeptide of von Willebrand factor circulates in blood and is identical to von Willebrand antigen II.</strong> Science 232: 995-998, 1986.">Fay et al. (1986)</a>; <a href="#Ginsburg1999" class="mim-tip-reference" title="Ginsburg, D. <strong>Molecular genetics of von Willebrand disease.</strong> Thromb. Haemost. 82: 585-591, 1999.">Ginsburg (1999)</a>; <a href="#Hoyer1981" class="mim-tip-reference" title="Hoyer, L. W. <strong>The factor VIII complex: structure and function.</strong> Blood 58: 1-13, 1981.">Hoyer
|
|
(1981)</a>; <a href="#Mazurier1990" class="mim-tip-reference" title="Mazurier, C., Gaucher, C., Jorieux, S., Parquet-Gernez, A., Goudemand, M. <strong>Evidence for a von Willebrand factor defect in factor VIII binding in three members of a family previously misdiagnosed mild haemophilia A and haemophilia A carriers: consequences for therapy and genetic counselling.</strong> Brit. J. Haemat. 76: 372-379, 1990.">Mazurier et al. (1990)</a>; <a href="#Meyer1978" class="mim-tip-reference" title="Meyer, D., McKee, P. A., Hoyer, L. W., Zimmerman, T. S., Gralnick, H. R. <strong>Molecular biology of factor VIII--von Willebrand factor.</strong> Thromb. Haemost. 40: 245-251, 1978.">Meyer et al. (1978)</a>; <a href="#Nachman1980" class="mim-tip-reference" title="Nachman, R. L., Jaffe, E. A., Miller, C., Brown, W. T. <strong>Structural analysis of factor VIII antigen in von Willebrand disease.</strong> Proc. Nat. Acad. Sci. 77: 6832-6836, 1980.">Nachman et al.
|
|
(1980)</a>; <a href="#Ngo1988" class="mim-tip-reference" title="Ngo, K. Y., Glotz, V. T., Koziol, J. A., Lynch, D. C., Gitschier, J., Ranieri, P., Ciavarella, N., Ruggeri, Z. M., Zimmerman, T. S. <strong>Homozygous and heterozygous deletions of the von Willebrand factor gene in patients and carriers of severe von Willebrand disease.</strong> Proc. Nat. Acad. Sci. 85: 2753-2757, 1988.">Ngo et al. (1988)</a>; <a href="#Ruggeri1982" class="mim-tip-reference" title="Ruggeri, Z. M., Nilsson, I. M., Lombardi, R., Holmberg, L., Zimmerman, T. S. <strong>Aberrant multimeric structure of von Willebrand factor in a new variant of von Willebrand's disease (type IIC).</strong> J. Clin. Invest. 70: 1124-1127, 1982.">Ruggeri et al. (1982)</a>; <a href="#Ruggeri1980" class="mim-tip-reference" title="Ruggeri, Z. M., Zimmerman, T. S. <strong>Variant von Willebrand's disease: characterization of two subtypes by analysis of multimeric composition of factor VIII-von Willebrand factor in plasma and platelets.</strong> J. Clin. Invest. 65: 1318-1325, 1980.">Ruggeri and
|
|
Zimmerman (1980)</a>; <a href="#Saba1985" class="mim-tip-reference" title="Saba, H. I., Saba, S. R., Dent, J., Ruggeri, Z. M., Zimmerman, T. S. <strong>Type IIB Tampa: a variant of von Willebrand disease with chronic thrombocytopenia, circulating platelet aggregates, and spontaneous platelet aggregation.</strong> Blood 66: 282-286, 1985.">Saba et al. (1985)</a>; <a href="#Verweij1985" class="mim-tip-reference" title="Verweij, C. L., de Vries, C. J. M., Distel, B., van Zonneveld, A.-J., Geurts van Kessel, A., van Mourik, J. A., Pannekoek, H. <strong>Construction of cDNA coding for human von Willebrand factor using antibody probes for colony-screening and mapping of the chromosomal gene.</strong> Nucleic Acids Res. 13: 4699-4717, 1985.">Verweij et al. (1985)</a>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Andrews1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Andrews, R. K., Booth, W. J., Gorman, J. J., Castaldi, P. A., Berndt, M. C.
|
|
<strong>Purification of botrocetin from Bothrops jararaca venom: analysis of the botrocetin-mediated interaction between von Willebrand factor and the human platelet membrane glycoprotein Ib-IX complex.</strong>
|
|
Biochemistry 28: 8317-8326, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2557900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2557900</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2557900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1021/bi00447a009" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Bahou1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bahou, W. F., Bowie, E. J. W., Fass, D. N., Ginsburg, D.
|
|
<strong>Molecular genetic analysis of porcine von Willebrand disease: tight linkage to the von Willebrand factor locus.</strong>
|
|
Blood 72: 308-313, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2898953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2898953</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2898953" 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="3" class="mim-anchor"></a>
|
|
<a id="Barrow1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Barrow, L. L., Simin, K., Mohlke, K., Nichols, W. C., Ginsburg, D., Meisler, M. H.
|
|
<strong>Conserved linkage of neurotrophin-3 and von Willebrand factor on mouse chromosome 6.</strong>
|
|
Mammalian Genome 4: 343-345, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8318738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8318738</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8318738" 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/BF00357095" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Bernardi1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bernardi, F., Marchetti, G., Guerra, S., Casonato, A., Gemmati, D., Patracchini, P., Ballerini, G., Conconi, F.
|
|
<strong>A de novo and heterozygous gene deletion causing a variant of von Willebrand disease.</strong>
|
|
Blood 75: 677-683, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1967540/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1967540</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1967540" 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="5" class="mim-anchor"></a>
|
|
<a id="Bodo2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bodo, I., Katsumi, A., Tuley, E. A., Eikenboom, J. C. J., Dong, Z., Sadler, J. E.
|
|
<strong>Type 1 von Willebrand disease mutation cys1149-to-arg causes intracellular retention and degradation of heterodimers: a possible general mechanism for dominant mutations of oligomeric proteins.</strong>
|
|
Blood 98: 2973-2979, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11698279/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11698279</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11698279" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood.v98.10.2973" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Bonthron1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bonthron, D., Orr, E. C., Mitsock, L. M., Ginsburg, D., Handin, R. I., Orkin, S. H.
|
|
<strong>Nucleotide sequence of pre-pro-von Willebrand factor cDNA.</strong>
|
|
Nucleic Acids Res. 14: 7125-7127, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3489923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3489923</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3489923" 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/nar/14.17.7125" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Bonthron1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bonthron, D. T., Handin, R. I., Kaufman, R. J., Wasley, L. C., Orr, E. C., Mitsock, L. M., Ewenstein, B., Loscalzo, J., Ginsburg, D., Orkin, S. H.
|
|
<strong>Structure of pre-pro-von Willebrand factor and its expression in heterologous cells.</strong>
|
|
Nature 324: 270-273, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3491324/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3491324</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3491324" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/324270a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Bowen2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bowen, D. J., Collins, P. W., Lester, W., Cumming, A. M., Keeney, S., Grundy, P., Enayat, S. M., Bolton-Maggs, P. H. B., Keeling, D. M., Khair, K., Tait, R. C., Wilde, J. T., Pasi, K. J., Hill, F. G.
|
|
<strong>The prevalence of the cysteine 1584 variant of von Willebrand factor is increased in type 1 von Willebrand disease: co-segregation with increased susceptibility to ADAMTS13 proteolysis but not clinical phenotype.</strong>
|
|
Brit. J. Haemat. 128: 830-836, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15755288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15755288</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15755288" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.2005.05375.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Bowen2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bowen, D. J., Collins, P. W.
|
|
<strong>An amino acid polymorphism in von Willebrand factor correlates with increased susceptibility to proteolysis by ADAMTS13.</strong>
|
|
Blood 103: 941-947, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14525793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14525793</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14525793" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2003-05-1505" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Cao2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cao, W., Krishnaswamy, S., Camire, R. M., Lenting, P. J., Zheng, X. L.
|
|
<strong>Factor VIII accelerates proteolytic cleavage of von Willebrand factor by ADAMTS13.</strong>
|
|
Proc. Nat. Acad. Sci. 105: 7416-7421, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18492805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18492805</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18492805[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=18492805" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0801735105" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Casonato2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Casonato, A., Pontara, E., Sartorello, F., Cattini, M. G., Sartori, M. T., Padrini, R., Girolami, A.
|
|
<strong>Reduced von Willebrand factor survival in type Vicenza von Willebrand disease.</strong>
|
|
Blood 99: 180-184, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11756169/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11756169</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11756169" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood.v99.1.180" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Castaman1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Castaman, G., Eikenboom, J. C. J., Bertina, R. M., Rodeghiero, F.
|
|
<strong>Inconsistency of association between type 1 von Willebrand disease phenotype and genotype in families identified in an epidemiological investigation.</strong>
|
|
Thromb. Haemost. 82: 1065-1070, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10494765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10494765</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10494765" 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="13" class="mim-anchor"></a>
|
|
<a id="Castaman2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Castaman, G., Rodeghiero, F., Mannucci, P. M.
|
|
<strong>The elusive pathogenesis of von Willebrand disease Vicenza. (Letter)</strong>
|
|
Blood 99: 4243-4244, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12043692/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12043692</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12043692" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood.v99.11.4243" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Collins1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Collins, C. J., Underdahl, J. P., Levene, R. B., Ravera, C. P., Morin, M. J., Dombalagian, M. J., Ricca, G., Livingston, D. M., Lynch, D. C.
|
|
<strong>Molecular cloning of the human gene for von Willebrand factor and identification of the transcription initiation site.</strong>
|
|
Proc. Nat. Acad. Sci. 84: 4393-4397, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3496594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3496594</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3496594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.84.13.4393" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Cooney1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cooney, K. A., Nichols, W. C., Bruck, M. E., Bahou, W. F., Shapiro, A. D., Bowie, E. J. W., Gralnick, H. R., Ginsburg, D.
|
|
<strong>The molecular defect in type IIB von Willebrand disease: identification of four potential missense mutations within the putative GpIb binding domain.</strong>
|
|
J. Clin. Invest. 87: 1227-1233, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1672694/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1672694</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1672694" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI115123" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Cumming2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cumming, A., Grundy, P., Keeney, S., Lester, W., Enayat, S., Guilliatt, A., Bowen, D., Pasi, J., Keeling, D., Hill, F., Bolton-Maggs, P. H., Hay, C., Collins, P. B.
|
|
<strong>An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease.</strong>
|
|
Thromb. Haemost. 96: 630-641, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17080221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17080221</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17080221" 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="17" class="mim-anchor"></a>
|
|
<a id="Cumming1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cumming, A. M., Armstrong, J. G., Pendry, K., Burn, A. M., Wensley, R. T.
|
|
<strong>Polymerase chain reaction amplification of two polymorphic simple repeat sequences within the von Willebrand factor gene: application to family studies in von Willebrand disease.</strong>
|
|
Hum. Genet. 89: 194-198, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1587530/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1587530</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1587530" 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/BF00217122" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Denis1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Denis, C., Methia, N., Frenette, P. S., Rayburn, H., Ullman-Cullere, M., Hynes, R. O., Wagner, D. D.
|
|
<strong>A mouse model of severe von Willebrand disease: defects in hemostasis and thrombosis.</strong>
|
|
Proc. Nat. Acad. Sci. 95: 9524-9529, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9689113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9689113</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9689113[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=9689113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.95.16.9524" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Dent1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dent, J. A., Berkowitz, S. D., Ware, J., Kasper, C. K., Ruggeri, Z. M.
|
|
<strong>Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 6306-6310, 1990. Note: Erratum: Proc. Nat. Acad. Sci. 87: 9508 only, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2385594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2385594</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2385594" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.87.16.6306" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Donner1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Donner, M., Andersson, A.-M., Kristoffersson, A.-C., Nilsson, I. M., Dahlback, B., Holmberg, L.
|
|
<strong>An arg545-to-cys substitution mutation of the von Willebrand factor in type IIB von Willebrand's disease.</strong>
|
|
Europ. J. Haemat. 47: 342-345, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1761120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1761120</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1761120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1600-0609.1991.tb01858.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Donner1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Donner, M., Kristoffersson, A. C., Lenk, H., Scheibel, E., Dahlback, B., Nilsson, I. M., Holmberg, L.
|
|
<strong>Type IIB von Willebrand's disease: gene mutations and clinical presentation in nine families from Denmark, Germany and Sweden.</strong>
|
|
Brit. J. Haemat. 82: 58-65, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1419803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1419803</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1419803" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1992.tb04594.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Eikenboom1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eikenboom, J. C. J., Castaman, G., Vos, H. L., Bertina, R. M., Rodeghiero, F.
|
|
<strong>Characterization of the genetic defects in recessive type 1 and type 3 von Willebrand disease patients of Italian origin.</strong>
|
|
Thromb. Haemost. 79: 709-717, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9569178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9569178</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9569178" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Eikenboom1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eikenboom, J. C. J., Matsushita, T., Reitsma, P. H., Tuley, E. A., Castaman, G., Briet, E., Sadler, J. E.
|
|
<strong>Dominant type 1 von Willebrand disease caused by mutated cysteine residues in the D3 domain of von Willebrand factor.</strong>
|
|
Blood 88: 2433-2441, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8839833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8839833</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8839833" 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="24" class="mim-anchor"></a>
|
|
<a id="Eikenboom1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eikenboom, J. C. J., Vink, T., Briet, E., Sixma, J. J., Reitsma, P. H.
|
|
<strong>Multiple substitutions in the von Willebrand factor gene that mimic the pseudogene sequence.</strong>
|
|
Proc. Nat. Acad. Sci. 91: 2221-2224, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8134377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8134377</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8134377" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.91.6.2221" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Fay1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fay, P. J., Kawai, Y., Wagner, D. D., Ginsburg, D., Bonthron, D., Ohlsson-Wilhelm, B. M., Chavin, S. I., Abraham, G. N., Handin, R. I., Orkin, S. H., Montgomery, R. R., Marder, V. J.
|
|
<strong>Propolypeptide of von Willebrand factor circulates in blood and is identical to von Willebrand antigen II.</strong>
|
|
Science 232: 995-998, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3486471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3486471</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3486471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.3486471" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Flood2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Flood, V. H., Gill, J. C., Morateck, P. A., Christopherson, P. A., Friedman, K. D., Haberichter, S. L., Branchford, B. R., Hoffmann, R. G., Abshire, T. C., Di Paola, J. A., Hoots, W. K, Leissinger, C., Lusher, J. M., Ragni, M. V., Shapiro, A. D., Montgomery, R. R.
|
|
<strong>:Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor.</strong>
|
|
Blood 116: 280-286, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20231421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20231421</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20231421[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=20231421" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2009-10-249102" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Gao2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gao, W., Anderson, P. J., Sadler, J. E.
|
|
<strong>Extensive contacts between ADAMTS13 exosites and von Willebrand factor domain A2 contribute to substrate specificity.</strong>
|
|
Blood 112: 1713-1719, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18492952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18492952</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18492952[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=18492952" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2008-04-148759" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Gaucher1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gaucher, C., Hanss, M., Dechavanne, M., Mazurier, C.
|
|
<strong>Substitution of cysteine for phenylalanine 751 in mature von Willebrand factor is a novel candidate mutation in a family with type IIA von Willebrand disease.</strong>
|
|
Brit. J. Haemat. 83: 94-99, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8435341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8435341</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8435341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1993.tb04637.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Gaucher1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gaucher, C., Jorieux, S., Mercier, B., Oufkir, D., Mazurier, C.
|
|
<strong>The 'Normandy' variant of von Willebrand disease: characterization of a point mutation in the von Willebrand factor gene.</strong>
|
|
Blood 77: 1937-1941, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2018834/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2018834</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2018834" 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="30" class="mim-anchor"></a>
|
|
<a id="Gaucher1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gaucher, C., Mercier, B., Jorieux, S., Oufkir, D., Mazurier, C.
|
|
<strong>Identification of two point mutations in the von Willebrand factor gene of three families with the 'Normandy' variant of von Willebrand disease.</strong>
|
|
Brit. J. Haemat. 78: 506-514, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1832934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1832934</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1832934" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1991.tb04480.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Ginsburg1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ginsburg, D., Handin, R. I., Bonthron, D. T., Donlon, T. A., Bruns, G. A. P., Latt, S. A., Orkin, S. H.
|
|
<strong>Human von Willebrand factor (vWF): isolation of complementary DNA (cDNA) clones and chromosomal localization.</strong>
|
|
Science 228: 1401-1406, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3874428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3874428</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3874428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.3874428" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Ginsburg1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ginsburg, D., Konkle, B. A., Gill, J. C., Montgomery, R. R., Bockenstedt, P. L., Johnson, T. A., Yang, A. Y.
|
|
<strong>Molecular basis of human von Willebrand disease: analysis of platelet von Willebrand factor mRNA.</strong>
|
|
Proc. Nat. Acad. Sci. 86: 3723-3727, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2786201/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2786201</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2786201" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.86.10.3723" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Ginsburg1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ginsburg, D., Sadler, J. E.
|
|
<strong>Von Willebrand disease: a database of point mutations, insertions, and deletions.</strong>
|
|
Thromb. Haemost. 69: 177-184, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8456431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8456431</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8456431" 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="34" class="mim-anchor"></a>
|
|
<a id="Ginsburg1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ginsburg, D.
|
|
<strong>Molecular genetics of von Willebrand disease.</strong>
|
|
Thromb. Haemost. 82: 585-591, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10605755/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10605755</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10605755" 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="35" class="mim-anchor"></a>
|
|
<a id="Golder2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Golder, M., Pruss, C. M., Hegadorn, C., Mewburn, J., Laverty, K., Sponagle, K., Lillicrap, D.
|
|
<strong>Mutation-specific hemostatic variability in mice expressing common type 2B von Willebrand disease substitutions.</strong>
|
|
Blood 115: 4862-4869, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20371742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20371742</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20371742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2009-11-253120" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Goodeve2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goodeve, A. C.
|
|
<strong>The genetic basis of von Willebrand disease.</strong>
|
|
Blood Rev. 24: 123-134, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20409624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20409624</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20409624" 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.blre.2010.03.003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Haberichter2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Haberichter, S. L., Budde, U., Obser, T., Schneppenheim, S., Wermes, C., Schneppenheim, R.
|
|
<strong>The mutation N528S in the von Willebrand factor (VWF) propeptide causes defective multimerization and storage of VWF.</strong>
|
|
Blood 115: 4580-4587, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20335223/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20335223</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20335223[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=20335223" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2009-09-244327" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Hagiwara1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hagiwara, T., Inaba, H., Yoshida, S., Nagaizumi, K., Arai, M., Hanabusa, H., Fukutake, K.
|
|
<strong>A novel mutation gly1672-to-arg in type 2A and a homozygous mutation in type 2B von Willebrand disease.</strong>
|
|
Thromb. Haemost. 76: 253-257, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8865541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8865541</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8865541" 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="39" class="mim-anchor"></a>
|
|
<a id="Hilbert2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hilbert, L., Jorieux, S., Fontenay-Roupie, M., Guicheteau, M., Fressinaud, E., Meyer, D., Mazurier, C., the INSERM Network on Molecular Abnormalities in von Willebrand Disease.
|
|
<strong>Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene.</strong>
|
|
Brit. J. Haemat. 127: 184-189, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15461624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15461624</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15461624" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.2004.05187.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Holmberg1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Holmberg, L., Berntorp, E., Donner, M., Nilsson, I. M.
|
|
<strong>von Willebrand's disease characterised by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers.</strong>
|
|
Blood 68: 668-672, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3488775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3488775</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3488775" 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="41" class="mim-anchor"></a>
|
|
<a id="Holmberg1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Holmberg, L., Dent, J. A., Schneppenheim, R., Budde, U., Ware, J., Ruggeri, Z. M.
|
|
<strong>von Willebrand factor mutation enhancing interaction with platelets in patients with normal multimeric structure.</strong>
|
|
J. Clin. Invest. 91: 2169-2177, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8486782/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8486782</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8486782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI116443" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Holmberg1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Holmberg, L., Karpman, D., Isaksson, C., Kristoffersson, A. C., Lethagen, S., Schneppenheim, R.
|
|
<strong>Ins405-asn-pro mutation in the von Willebrand factor propeptide in recessive type 2A (IIC) von Willebrand's disease.</strong>
|
|
Thromb. Haemost. 79: 718-722, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9569179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9569179</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9569179" 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="43" class="mim-anchor"></a>
|
|
<a id="Howard1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Howard, M. A., Perkin, J., Salem, H. H., Firkin, B. G.
|
|
<strong>The agglutination of human platelets by botrocetin: evidence that botrocetin and ristocetin act at different sites on the factor VIII molecule and platelet membrane.</strong>
|
|
Brit. J. Haemat. 57: 25-35, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6426499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6426499</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6426499" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1984.tb02862.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Hoyer1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hoyer, L. W.
|
|
<strong>The factor VIII complex: structure and function.</strong>
|
|
Blood 58: 1-13, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6165414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6165414</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6165414" 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="45" class="mim-anchor"></a>
|
|
<a id="Huizinga2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Huizinga, E. G., Tsuji, S., Romijn, R. A. P., Schiphorst, M. E., de Groot, P. G., Sixma, J. J., Gros, P.
|
|
<strong>Structures of glycoprotein Ib-alpha and its complex with von Willebrand factor A1 domain.</strong>
|
|
Science 297: 1176-1179, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12183630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12183630</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12183630" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.107355" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Iannuzzi1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Iannuzzi, M. C., Hidaka, N., Boehnke, M., Bruck, M. E., Hanna, W. T., Collins, F. S., Ginsburg, D.
|
|
<strong>Analysis of the relationship of von Willebrand disease (vWD) and hereditary hemorrhagic telangiectasia and identification of a potential type IIA vWD mutation (ile865-to-thr).</strong>
|
|
Am. J. Hum. Genet. 48: 757-763, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1673047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1673047</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1673047" 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="47" class="mim-anchor"></a>
|
|
<a id="Jackson2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jackson, S. C., Sinclair, G. D., Cloutier, S., Duan, Z., Rand, M. L., Poon, M.-C.
|
|
<strong>The Montreal platelet syndrome kindred has type 2B von Willebrand disease with the VWF V1316M mutation.</strong>
|
|
Blood 113: 3348-3351, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19060241/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19060241</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19060241" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2008-06-165233" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Kokame2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kokame, K., Matsumoto, M., Fujimura, Y., Miyata, T.
|
|
<strong>VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS-13.</strong>
|
|
Blood 103: 607-612, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14512308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14512308</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14512308" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2003-08-2861" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Kyrle1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kyrle, P. A., Niessner, H., Dent, J., Panzer, S., Brenner, B., Zimmerman, T. S., Lechner, K.
|
|
<strong>IIB von Willebrand's disease: pathogenetic and therapeutic studies.</strong>
|
|
Brit. J. Haemat. 69: 55-59, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3132965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3132965</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3132965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1988.tb07602.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="50" class="mim-anchor"></a>
|
|
<a id="Lavergne1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lavergne, J.-M., De Paillette, L., Bahnak, B. R., Ribba, A.-S., Fressinaud, E., Meyer, D., Pietu, G.
|
|
<strong>Defects in type IIA von Willebrand disease: a cysteine 509 to arginine substitution in the mature von Willebrand factor disrupts a disulphide loop involved in the interaction with platelet glycoprotein Ib-IX.</strong>
|
|
Brit. J. Haemat. 82: 66-72, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1419804/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1419804</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1419804" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1992.tb04595.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Lester2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lester, W. A., Guilliatt, A. M., Surdhar, G. K., Enayat, S. M., Wilde, J. T., Willoughby, S., Grundy, P., Cumming, A. M., Collins, P. W., Hill, F. G. H.
|
|
<strong>Inherited and de novo von Willebrand disease 'Vicenza' in UK families with the R1205H mutation: diagnostic pitfalls and new insights.</strong>
|
|
Brit. J. Haemat. 135: 91-96, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16925796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16925796</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16925796" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.2006.06251.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Lynch1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lynch, D. C., Zimmerman, T. S., Collins, C. J., Morin, M. J., Ling, E. H., Livingston, D. M.
|
|
<strong>Molecular cloning of mRNA for human von Willebrand factor. (Abstract)</strong>
|
|
Clin. Res. 33: 548, 1985.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Lynch1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lynch, D. C., Zimmerman, T. S., Ruggeri, Z. M.
|
|
<strong>Von Willebrand factor, now cloned. (Annotation).</strong>
|
|
Brit. J. Haemat. 64: 15-20, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3489483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3489483</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3489483" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1986.tb07569.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Mancuso1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mancuso, D. J., Tuley, E. A., Westfield, L. A., Lester-Mancuso, T. L., Le Beau, M. M., Sorace, J. M., Sadler, J. E.
|
|
<strong>Human von Willebrand factor gene and pseudogene: structural analysis and differentiation by polymerase chain reaction.</strong>
|
|
Biochemistry 30: 253-269, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1988024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1988024</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1988024" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1021/bi00215a036" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Mancuso1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mancuso, D. J., Tuley, E. A., Westfield, L. A., Worrall, N. K., Shelton-Inloes, B. B., Sorace, J. M., Alevy, Y. G., Sadler, J. E.
|
|
<strong>Structure of the gene for human von Willebrand factor.</strong>
|
|
J. Biol. Chem. 264: 19514-19527, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2584182/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2584182</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2584182" 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="56" class="mim-anchor"></a>
|
|
<a id="Mannucci1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mannucci, P. M., Lombardi, R., Castaman, G., Dent, J. A., Lattuada, A., Rodeghiero, F., Zimmerman, T. S.
|
|
<strong>Von Willebrand disease 'Vicenza' with larger-than-normal (supranormal) von Willebrand factor multimers.</strong>
|
|
Blood 71: 65-70, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3257148/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3257148</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3257148" 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="57" class="mim-anchor"></a>
|
|
<a id="Mazurier1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mazurier, C., Dieval, J., Jorieux, S., Delobel, J., Goudemand, M.
|
|
<strong>A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF: characterization of abnormal vWF/FVIII interaction.</strong>
|
|
Blood 75: 20-26, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2104761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2104761</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2104761" 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="58" class="mim-anchor"></a>
|
|
<a id="Mazurier1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mazurier, C., Gaucher, C., Jorieux, S., Parquet-Gernez, A., Goudemand, M.
|
|
<strong>Evidence for a von Willebrand factor defect in factor VIII binding in three members of a family previously misdiagnosed mild haemophilia A and haemophilia A carriers: consequences for therapy and genetic counselling.</strong>
|
|
Brit. J. Haemat. 76: 372-379, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2124499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2124499</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2124499" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1990.tb06371.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="59" class="mim-anchor"></a>
|
|
<a id="Mazurier2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mazurier, C., Parquet-Gernez, A., Gaucher, C., Lavergne, J.-M., Goudemand, J.
|
|
<strong>Factor VIII deficiency not induced by FVIII gene mutation in a female first cousin of two brothers with haemophilia A.</strong>
|
|
Brit. J. Haemat. 119: 390-392, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12406074/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12406074</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12406074" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2141.2002.03819.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="60" class="mim-anchor"></a>
|
|
<a id="Mertes1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mertes, G., Ludwig, M., Schwaab, R., Brackmann, H.-H., Olek, K.
|
|
<strong>Delta C in exon 18 of the von Willebrand gene is uncommon in German vWD type III patients. (Letter)</strong>
|
|
Thromb. Haemost. 70: 1064-1065, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8165603/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8165603</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8165603" 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="61" class="mim-anchor"></a>
|
|
<a id="Meyer1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meyer, D., McKee, P. A., Hoyer, L. W., Zimmerman, T. S., Gralnick, H. R.
|
|
<strong>Molecular biology of factor VIII--von Willebrand factor.</strong>
|
|
Thromb. Haemost. 40: 245-251, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/310584/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">310584</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=310584" 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="62" class="mim-anchor"></a>
|
|
<a id="Michaux2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Michaux, G., Abbitt, K. B., Collinson, L. M., Haberichter, S. L., Norman, K. E., Cutler, D. F.
|
|
<strong>The physiological function of von Willebrand's factor depends on its tubular storage in endothelial Weibel-Palade bodies.</strong>
|
|
Dev. Cell 10: 223-232, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16459301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16459301</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16459301" 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.devcel.2005.12.012" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="63" class="mim-anchor"></a>
|
|
<a id="Milton1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Milton, J. G., Frojmovic, M. M., Tang, S. S., White, J. G.
|
|
<strong>Spontaneous platelet aggregation in a hereditary giant platelet syndrome (MPS).</strong>
|
|
Am. J. Path. 114: 336-345, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6696046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6696046</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6696046" 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="64" class="mim-anchor"></a>
|
|
<a id="Murray1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Murray, E. W., Giles, A. R., Lillicrap, D.
|
|
<strong>Germ-line mosaicism for a valine-to-methionine substitution at residue 553 in the glycoprotein Ib-binding domain of von Willebrand factor, causing type IIB von Willebrand disease.</strong>
|
|
Am. J. Hum. Genet. 50: 199-207, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1729889/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1729889</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1729889" 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="65" class="mim-anchor"></a>
|
|
<a id="Nachman1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nachman, R. L., Jaffe, E. A., Miller, C., Brown, W. T.
|
|
<strong>Structural analysis of factor VIII antigen in von Willebrand disease.</strong>
|
|
Proc. Nat. Acad. Sci. 77: 6832-6836, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6161373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6161373</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6161373" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.77.11.6832" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="66" class="mim-anchor"></a>
|
|
<a id="Ngo1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ngo, K. Y., Glotz, V. T., Koziol, J. A., Lynch, D. C., Gitschier, J., Ranieri, P., Ciavarella, N., Ruggeri, Z. M., Zimmerman, T. S.
|
|
<strong>Homozygous and heterozygous deletions of the von Willebrand factor gene in patients and carriers of severe von Willebrand disease.</strong>
|
|
Proc. Nat. Acad. Sci. 85: 2753-2757, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3258663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3258663</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3258663" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.85.8.2753" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="67" class="mim-anchor"></a>
|
|
<a id="{NIH/CEPH Collaborative Mapping Group}1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
NIH/CEPH Collaborative Mapping Group.
|
|
<strong>A comprehensive genetic linkage map of the human genome.</strong>
|
|
Science 258: 67-86, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1439770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1439770</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1439770" 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="68" class="mim-anchor"></a>
|
|
<a id="O'Brien2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
O'Brien, L. A., James, P. D., Othman, M., Berber, E., Cameron, C., Notley, C. R. P., Hegadorn, C. A., Sutherland, J. J., Hough, C., Rivard, G. E., O'Shaunessey, D., Association of Hemophilia Clinic Directors of Canada, Lillicrap, D.
|
|
<strong>Founder von Willebrand factor haplotype associated with type I von Willebrand disease.</strong>
|
|
Blood 102: 549-557, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12649144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12649144</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12649144" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2002-12-3693" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="69" class="mim-anchor"></a>
|
|
<a id="Patracchini1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Patracchini, P., Marchetti, G., Aiello, V., Croci, G., Calzolari, E., Bernardi, F.
|
|
<strong>Characterization and mapping of the 5-prime portion of von Willebrand factor pseudogene.</strong>
|
|
Hum. Genet. 90: 297-298, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1487245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1487245</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1487245" 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/BF00220083" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="70" class="mim-anchor"></a>
|
|
<a id="Peake1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Peake, I. R., Liddell, M. B., Moodie, P., Standen, G., Mancuso, D. J., Tuley, E. A., Westfield, L. A., Sorace, J. M., Sadler, J. E., Verweij, C. L., Bloom, A. L.
|
|
<strong>Severe type III von Willebrand's disease caused by deletion of exon 42 of the von Willebrand factor gene: family studies that identify carriers of the condition and a compound heterozygous individual.</strong>
|
|
Blood 75: 654-661, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2297569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2297569</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2297569" 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="71" class="mim-anchor"></a>
|
|
<a id="Peerlinck1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Peerlinck, K., Eikenboom, J. C. J., Ploos Van Amstel, H. K., Sangtawesin, W., Arnout, J., Reitsma, P. H., Vermylen, J., Briet, E.
|
|
<strong>A patient with von Willebrand's disease characterized by a compound heterozygosity for a substitution of arg-854 by gln in the putative factor-VIII-binding domain of von Willebrand factor (vWF) on one allele and very low levels of mRNA from the second vWF allele.</strong>
|
|
Brit. J. Haemat. 80: 358-363, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1581215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1581215</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1581215" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1992.tb08145.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="72" class="mim-anchor"></a>
|
|
<a id="Rabinowitz1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rabinowitz, I., Tuley, E. A., Mancuso, D. J., Randi, A. M., Firkin, B. G., Howard, M. A., Sadler, J. E.
|
|
<strong>Von Willebrand disease type B: a missense mutation selectively abolishes ristocetin-induced von Willebrand factor binding to platelet glycoprotein Ib.</strong>
|
|
Proc. Nat. Acad. Sci. 89: 9846-9849, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1409710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1409710</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1409710" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.89.20.9846" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="73" class="mim-anchor"></a>
|
|
<a id="Randi1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Randi, A. M., Rabinowitz, I., Mancuso, D. J., Mannucci, P. M., Sadler, J. E.
|
|
<strong>Molecular basis of von Willebrand disease type IIB: candidate mutations cluster in one disulfide loop between proposed platelet glycoprotein Ib binding sequences.</strong>
|
|
J. Clin. Invest. 87: 1220-1226, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2010538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2010538</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2010538" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI115122" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="74" class="mim-anchor"></a>
|
|
<a id="Randi1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Randi, A. M., Sacchi, E., Castaman, G. C., Rodeghiero, F., Mannucci, P. M.
|
|
<strong>The genetic defect of type I von Willebrand disease 'Vicenza' is linked to the von Willebrand factor gene.</strong>
|
|
Thromb. Haemost. 69: 173-176, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8456430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8456430</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8456430" 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="75" class="mim-anchor"></a>
|
|
<a id="Rayes2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rayes, J., Hollestelle, M. J., Legendre, P., Marx, I., de Groot, P. G., Christophe, O. D., Lenting, P. J., Denis, C. V.
|
|
<strong>Mutation and ADAMTS13-dependent modulation of disease severity in a mouse model for von Willebrand disease type 2B.</strong>
|
|
Blood 115: 4870-4877, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20200350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20200350</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20200350" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2009-11-254193" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="76" class="mim-anchor"></a>
|
|
<a id="Riddell2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Riddell, A. F., Gomez, K., Millar, C. M., Mellars, G., Gill, S., Brown, S. A., Sutherland, M., Laffan, M. A., McKinnon, T. A.
|
|
<strong>Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor.</strong>
|
|
Blood 114: 3489-3496, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19687512/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19687512</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19687512" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2008-10-184317" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="77" class="mim-anchor"></a>
|
|
<a id="Ruggeri1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M., Lombardi, R., Gatti, L., Bader, R., Valsecchi, C., Zimmerman, T. S.
|
|
<strong>Type IIB von Willebrand's disease: differential clearance of endogenous versus transfused large multimer von Willebrand factor.</strong>
|
|
Blood 60: 1453-1456, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6982737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6982737</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6982737" 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="78" class="mim-anchor"></a>
|
|
<a id="Ruggeri1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M., Nilsson, I. M., Lombardi, R., Holmberg, L., Zimmerman, T. S.
|
|
<strong>Aberrant multimeric structure of von Willebrand factor in a new variant of von Willebrand's disease (type IIC).</strong>
|
|
J. Clin. Invest. 70: 1124-1127, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6982283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6982283</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6982283" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/jci110700" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="79" class="mim-anchor"></a>
|
|
<a id="Ruggeri1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M., Pareti, F. I., Mannucci, P. M., Ciavarella, N., Zimmerman, T. S.
|
|
<strong>Heightened interaction between platelets and factor VIII von Willebrand factor in a new subtype of von Willebrand's disease.</strong>
|
|
New Eng. J. Med. 302: 1047-1051, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6767976/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6767976</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6767976" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM198005083021902" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="80" class="mim-anchor"></a>
|
|
<a id="Ruggeri1980" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M., Zimmerman, T. S.
|
|
<strong>Variant von Willebrand's disease: characterization of two subtypes by analysis of multimeric composition of factor VIII-von Willebrand factor in plasma and platelets.</strong>
|
|
J. Clin. Invest. 65: 1318-1325, 1980.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6773982/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6773982</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6773982" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI109795" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="81" class="mim-anchor"></a>
|
|
<a id="Ruggeri1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M.
|
|
<strong>Von Willebrand factor.</strong>
|
|
J. Clin. Invest. 99: 559-564, 1997. Note: Erratum: J. Clin. Invest. 100: 237 only, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9045854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9045854</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9045854" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI119195" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="82" class="mim-anchor"></a>
|
|
<a id="Saba1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Saba, H. I., Saba, S. R., Dent, J., Ruggeri, Z. M., Zimmerman, T. S.
|
|
<strong>Type IIB Tampa: a variant of von Willebrand disease with chronic thrombocytopenia, circulating platelet aggregates, and spontaneous platelet aggregation.</strong>
|
|
Blood 66: 282-286, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3926021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3926021</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3926021" 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="83" class="mim-anchor"></a>
|
|
<a id="Sadler2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others.
|
|
<strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong>
|
|
J. Thromb. Haemost. 4: 2103-2114, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16889557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16889557</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16889557" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1538-7836.2006.02146.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="84" class="mim-anchor"></a>
|
|
<a id="Sadler1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sadler, J. E., Ginsburg, D.
|
|
<strong>A database of polymorphisms in the von Willebrand factor gene and pseudogene.</strong>
|
|
Thromb. Haemost. 69: 185-191, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8456432/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8456432</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8456432" 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="85" class="mim-anchor"></a>
|
|
<a id="Sadler1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sadler, J. E., Shelton-Inloes, B. B., Sorace, J. M., Harlan, J. M., Titani, K., Davie, E. W.
|
|
<strong>Cloning and characterization of two cDNAs coding for human von Willebrand factor.</strong>
|
|
Proc. Nat. Acad. Sci. 82: 6394-6398, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2864688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2864688</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2864688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.82.19.6394" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="86" class="mim-anchor"></a>
|
|
<a id="Schneppenheim1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schneppenheim, R., Brassard, J., Krey, S., Budde, U., Kunicki, T. J., Holmberg, L., Ware, J., Ruggeri, Z. M.
|
|
<strong>Defective dimerization of von Willebrand factor subunits due to a cys-to-arg mutation in type IID von Willebrand disease.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 3581-3586, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8622978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8622978</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8622978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.93.8.3581" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="87" class="mim-anchor"></a>
|
|
<a id="Schneppenheim2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schneppenheim, R., Federici, A. B., Budde, U., Castaman, G., Drewke, E., Krey, S., Mannucci, P. M., Riesen, G., Rodeghiero, F., Zieger, B., Zimmermann, R.
|
|
<strong>Von Willebrand disease type 2M 'Vicenza' in Italian and German patients: identification of the first candidate mutation (G3864A; R1205H) in 8 families.</strong>
|
|
Thromb. Haemost. 83: 136-140, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10669167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10669167</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10669167" 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="88" class="mim-anchor"></a>
|
|
<a id="Schneppenheim2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schneppenheim, R., Michiels, J. J., Obser, T., Oyen, F., Pieconka, A., Schneppenheim, S., Will, K., Zieger, B., Budde, U.
|
|
<strong>A cluster of mutations in the D3 domain of von Willebrand factor correlates with a distinct subgroup of von Willebrand disease: type 2A/IIE.</strong>
|
|
Blood 115: 4894-4901, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20351307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20351307</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20351307" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2009-07-226324" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="89" class="mim-anchor"></a>
|
|
<a id="Schneppenheim1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schneppenheim, R., Thomas, K. B., Krey, S., Budde, U., Jessat, U., Sutor, A. H., Zieger, B.
|
|
<strong>Identification of a candidate missense mutation in a family with von Willebrand disease type IIC.</strong>
|
|
Hum. Genet. 95: 681-686, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7789955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7789955</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7789955" 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/BF00209487" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="90" class="mim-anchor"></a>
|
|
<a id="Shelton-Inloes1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shelton-Inloes, B. B., Chehab, F. F., Mannucci, P. M., Federici, A. B., Sadler, J. E.
|
|
<strong>Gene deletions correlate with the development of alloantibodies in von Willebrand disease.</strong>
|
|
J. Clin. Invest. 79: 1459-1465, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3033024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3033024</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3033024" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI112974" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="91" class="mim-anchor"></a>
|
|
<a id="Sporn1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sporn, L. A., Marder, V. J., Wagner, D. D.
|
|
<strong>Von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively.</strong>
|
|
Blood 69: 1531-1534, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3105624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3105624</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3105624" 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="92" class="mim-anchor"></a>
|
|
<a id="Stepanian2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stepanian, A., Ribba, A.-S., Lavergne, J.-M., Fressinaud, E., Juhan-Vague, I., Mazurier, C., Girma, J.-P., Meyer, D.
|
|
<strong>A new mutation, S1285F, within the A1 loop of von Willebrand factor induces a conformational change in A1 loop with abnormal binding to platelet GPIb and botrocetin causing type 2M von Willebrand disease.</strong>
|
|
Brit. J. Haemat. 120: 643-651, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12588351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12588351</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12588351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2141.2003.04168.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="93" class="mim-anchor"></a>
|
|
<a id="Sutherland2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sutherland, M. S., Cumming, A. M., Bowman, M., Bolton-Maggs, P. H. B., Bowen, D. J., Collins, P. W., Hay, C. R. M., Will, A. M., Keeney, S.
|
|
<strong>A novel deletion mutation is recurrent in von Willebrand disease types 1 and 3.</strong>
|
|
Blood 114: 1091-1098, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19372260/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19372260</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19372260" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2008-08-173278" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="94" class="mim-anchor"></a>
|
|
<a id="Titani1986" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Titani, K., Kumar, S., Takio, K., Ericsson, L. H., Wade, R. D., Ashida, K., Walsh, K. A., Chopek, M. W., Sadler, J. E., Fujikawa, K.
|
|
<strong>Amino acid sequence of human von Willebrand factor.</strong>
|
|
Biochemistry 25: 3171-3184, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3524673/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3524673</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3524673" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1021/bi00359a015" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="95" class="mim-anchor"></a>
|
|
<a id="Tjernberg2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tjernberg, P., Castaman, G., Vos, H. L., Bertina, R. M., Eikenboom, J. C.
|
|
<strong>Homozygous C2362F von Willebrand factor induces intracellular retention of mutant von Willebrand factor resulting in autosomal recessive severe von Willebrand disease.</strong>
|
|
Brit. J. Haemat. 133: 409-418, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16643449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16643449</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16643449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.2006.06055.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="96" class="mim-anchor"></a>
|
|
<a id="Tuley1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tuley, E. A., Gaucher, C., Jorieux, S., Worrall, N. K., Sadler, J. E., Mazurier, C.
|
|
<strong>Expression of von Willebrand factor 'Normandy': an autosomal mutation that mimics hemophilia A.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 6377-6381, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1906179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1906179</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1906179" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.88.14.6377" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="97" class="mim-anchor"></a>
|
|
<a id="Verweij1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Verweij, C. L., de Vries, C. J. M., Distel, B., van Zonneveld, A.-J., Geurts van Kessel, A., van Mourik, J. A., Pannekoek, H.
|
|
<strong>Construction of cDNA coding for human von Willebrand factor using antibody probes for colony-screening and mapping of the chromosomal gene.</strong>
|
|
Nucleic Acids Res. 13: 4699-4717, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3875078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3875078</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3875078" 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/nar/13.13.4699" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="98" class="mim-anchor"></a>
|
|
<a id="Verweij1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Verweij, C. L., Hofker, M., Quadt, R., Briet, E., Pannekoek, H.
|
|
<strong>RFLP for a human von Willebrand factor (vWF) cDNA clone, pvWF1100.</strong>
|
|
Nucleic Acids Res. 13: 8289 only, 1985. Note: Erratum: Nucleic Acids Res. 14: 1930 only, 1986.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3877913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3877913</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3877913" 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/nar/13.22.8289" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="99" class="mim-anchor"></a>
|
|
<a id="von Willebrand1926" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
von Willebrand, E. A.
|
|
<strong>Hereditar pseudohemofili.</strong>
|
|
Finska Lakar. Hand. 68: 87-112, 1926.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="100" class="mim-anchor"></a>
|
|
<a id="Wagner1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wagner, D. D., Saffaripour, S., Bonfanti, R., Sadler, J. E., Cramer, E. M., Chapman, B., Mayadas, T. N.
|
|
<strong>Induction of specific storage organelles by von Willebrand factor propolypeptide.</strong>
|
|
Cell 64: 403-413, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1988154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1988154</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1988154" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(91)90648-i" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="101" class="mim-anchor"></a>
|
|
<a id="Ware1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ware, J., Dent, J. A., Azuma, H., Sugimoto, M., Kyrle, P. A., Yoshioka, A., Ruggeri, Z. M.
|
|
<strong>Identification of a point mutation in type IIB von Willebrand disease illustrating the regulation of von Willebrand factor affinity for the platelet membrane glycoprotein Ib-IX receptor.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 2946-2950, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2011604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2011604</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2011604" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.88.7.2946" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="102" class="mim-anchor"></a>
|
|
<a id="Weiss1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Weiss, J. G., Sussman, I. I.
|
|
<strong>Increased ristocetin-induced platelet aggregation (RIPA) and plasma von Willebrand factor (VWF) containing all VWF multimers (type I--New York). (Abstract)</strong>
|
|
Blood 66 (suppl. 1): 329, 1985.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="103" class="mim-anchor"></a>
|
|
<a id="Wise1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wise, R. J., Ewenstein, B. M., Gorlin, J., Narins, S. C., Jesson, M., Handin, R. I.
|
|
<strong>Autosomal recessive transmission of hemophilia A due to a von Willebrand factor mutation.</strong>
|
|
Hum. Genet. 91: 367-372, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8500791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8500791</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8500791" 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/BF00217358" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="104" class="mim-anchor"></a>
|
|
<a id="Wu2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wu, J.-J., Fujikawa, K., McMullen, B. A., Chung, D. W.
|
|
<strong>Characterization of a core binding site for ADAMTS-13 in the A2 domain of von Willebrand factor.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 18470-18474, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17121983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17121983</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17121983[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=17121983" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0609190103" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="105" class="mim-anchor"></a>
|
|
<a id="Wylie1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wylie, B., Gibson, J., Uhr, E., Kronenberg, H.
|
|
<strong>Von Willebrand's disease characterized by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers in plasma: a new subtype.</strong>
|
|
Pathology 20: 62-63, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3259690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3259690</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3259690" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.3109/00313028809085199" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="106" class="mim-anchor"></a>
|
|
<a id="Zhang1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhang, Z. P., Blomback, M., Nyman, D., Anvret, M.
|
|
<strong>Mutations of von Willebrand factor gene in families with von Willebrand disease in the Aland Islands.</strong>
|
|
Proc. Nat. Acad. Sci. 90: 7937-7940, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8367445/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8367445</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8367445" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.90.17.7937" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="107" class="mim-anchor"></a>
|
|
<a id="Zhang1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhang, Z. P., Falk, G., Blomback, M., Egberg, N., Anvret, M.
|
|
<strong>A single cytosine deletion in exon 18 of the von Willebrand factor gene is the most common mutation in Swedish vWD type III patients.</strong>
|
|
Hum. Molec. Genet. 1: 767-768, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1302613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1302613</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1302613" 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/1.9.767" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="108" class="mim-anchor"></a>
|
|
<a id="Zhang1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhang, Z. P., Falk, G., Blomback, M., Egberg, N., Anvret, M.
|
|
<strong>Identification of a new nonsense mutation in the von Willebrand factor gene in patients with von Willebrand disease type III.</strong>
|
|
Hum. Molec. Genet. 1: 61-62, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301136</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1301136" 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/1.1.61" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="109" class="mim-anchor"></a>
|
|
<a id="Zhang1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhang, Z. P., Lindstedt, M., Falk, G., Blomback, M., Egberg, N., Anvret, M.
|
|
<strong>Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I.</strong>
|
|
Am. J. Hum. Genet. 51: 850-858, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1415226/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1415226</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1415226" 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="110" class="mim-anchor"></a>
|
|
<a id="Zhou2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhou, M., Dong, X., Baldauf, C., Chen, H., Zhou, Y., Springer, T. A., Luo, X., Zhong, C., Grater, F., Ding, J.
|
|
<strong>A novel calcium-binding site of von Willebrand factor A2 domain regulates its cleavage by ADAMTS13.</strong>
|
|
Blood 117: 4623-4631, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21385852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21385852</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21385852" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1182/blood-2010-11-321596" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="111" class="mim-anchor"></a>
|
|
<a id="Zieger1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zieger, B., Budde, U., Jessat, U., Zimmermann, R., Simon, M., Katzel, R., Sutor, A. H.
|
|
<strong>New families with von Willebrand disease type 2M (Vicenza).</strong>
|
|
Thromb. Res. 87: 57-64, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9253800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9253800</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9253800" 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/s0049-3848(97)00104-7" 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">
|
|
Bao Lige - updated : 09/19/2019
|
|
</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">
|
|
Cassandra L. Kniffin - updated : 4/29/2013<br>Cassandra L. Kniffin - updated : 5/10/2011<br>Cassandra L. Kniffin - updated : 12/27/2010<br>Cassandra L. Kniffin - updated : 10/8/2010
|
|
</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">
|
|
Cassandra L. Kniffin : 12/1/2009
|
|
</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 : 01/07/2025
|
|
</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 : 07/28/2023<br>carol : 07/27/2023<br>mgross : 09/19/2019<br>mgross : 09/19/2019<br>alopez : 11/07/2018<br>carol : 08/04/2016<br>carol : 07/07/2016<br>joanna : 6/29/2016<br>alopez : 5/21/2015<br>mgross : 11/18/2014<br>carol : 3/18/2014<br>alopez : 5/3/2013<br>ckniffin : 4/29/2013<br>carol : 4/18/2013<br>carol : 4/18/2013<br>terry : 4/4/2013<br>terry : 8/9/2012<br>carol : 7/6/2011<br>wwang : 6/13/2011<br>ckniffin : 5/10/2011<br>carol : 4/7/2011<br>terry : 1/7/2011<br>wwang : 1/5/2011<br>ckniffin : 12/27/2010<br>wwang : 11/2/2010<br>ckniffin : 10/8/2010<br>ckniffin : 10/8/2010<br>carol : 10/5/2010<br>carol : 10/4/2010<br>ckniffin : 9/29/2010<br>ckniffin : 12/4/2009
|
|
</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> 613160
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
VON WILLEBRAND FACTOR; VWF
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
FACTOR VIII-VON WILLEBRAND FACTOR; F8VWF
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: VWF</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 128106003, 128108002, 359711001, 359717002, 359732009;
|
|
|
|
|
|
<strong>ICD10CM:</strong> D68.01, D68.020, D68.021, D68.022, D68.023, D68.03;
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 12p13.31
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 12:5,948,877-6,124,670 </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">
|
|
12p13.31
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
von Willebrand disease, type 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
193400
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
von Willebrand disease, type 3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
277480
|
|
</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">
|
|
von Willebrand disease, types 2A, 2B, 2M, and 2N
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613554
|
|
</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>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The VWF gene encodes von Willebrand factor (VWF), a large multimeric glycoprotein that plays a central role in the blood coagulation system, serving both as a major mediator of platelet-vessel wall interaction and platelet adhesion, and as a carrier for coagulation factor VIII (F8; 300841). Diminished or abnormal VWF activity results in von Willebrand disease (VWD; see 193400), a common and complex hereditary bleeding disorder (Ginsburg et al., 1985). </p><p>The receptor for von Willebrand factor is a large complex comprising 4 proteins: glycoprotein Ib (GP1BA; 606672 and GP1BB; 138720), platelet glycoprotein IX (GP9; 173515) and platelet glycoprotein V (GP5; 173511).</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>Ginsburg et al. (1985) isolated overlapping cDNA clones corresponding to the human VWF gene. The 8.2-kb transcript accounted for approximately 0.3% of endothelial cell mRNA, but was undetectable in several other tissues examined. </p><p>Sadler et al. (1985) isolated cDNA clones from cultured human umbilical vein endothelial cells. Two inserts, which together coded for about 80% of the protein, were identified. One corresponded to residues 1 to 110 of the circulating mature protein and the second coded for 1,525 residues at the C terminus; there was about a 350-residue gap between the 2 clones. At least 3 separate polypeptide segments showed evidence of internal duplication, suggesting a complex evolutionary history. The full-length mature protein contains 2,050 amino acids (Titani et al., 1986). </p><p>Bonthron et al. (1986) presented the nucleotide sequence of pre-pro-von Willebrand factor cDNA. </p><p>Lynch et al. (1985) also cloned the VWF gene, and Lynch et al. (1986) stated that 4 separate groups had reported isolation of VWF-specific clones from human endothelial cell cDNA libraries. </p><p>VWF is synthesized in endothelial cells and megakaryocytes as a 2,813-residue pre-protein. It dimerizes, undergoes extensive posttranslational modification, and is packaged as a mature protein into endothelial cell Weibel-Palade bodies and platelet alpha granules. Endothelial cells secrete VWF constitutively, whereas platelets release VWF when stimulated. Circulating VWF multimers are composed of up to 40 subunits and range in size from 500 to 10,000 kD (review by Goodeve, 2010). VWF is synthesized in megakaryocytes and endothelial cells with a 22-amino acid signal peptide, 741-amino acid propeptide and 2,050-amino acid mature VWF (review by Goodeve, 2010). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Mancuso et al. (1989) concluded that the VWF gene is approximately 178 kb long and contains 52 exons. The exons vary from 40 to 1379 bp, and the introns from 97 bp to approximately 19.9 kb. The signal peptide and propeptide (von Willebrand antigen II) are encoded by 17 exons in approximately 80 kb of DNA, while the mature subunit of von Willebrand factor and the 3-prime noncoding region are encoded by 35 exons in the remainder of the gene. A number of repetitive sequences were identified, including 14 Alu repeats and a polymorphic TCTA simple repeat of about 670 bp in intron 40. Regions of the gene that encode homologous domains have similar structures, supporting a model for their origin by gene segment duplication. </p><p>From a study of a series of overlapping cosmid genomic clones of VWF, Collins et al. (1987) identified the transcription initiation site, a portion of the promoter region, and the translation termination codon. Their evidence supported the existence of a single VWF gene in the haploid genome. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Verweij et al. (1985) cloned the gene for VWF and assigned it to chromosome 12 using cDNA probes with panels of human-rodent hybrid cells. </p><p>By somatic cell hybridization and in situ hybridization using a cDNA clone of the gene, Ginsburg et al. (1985) assigned the VWF gene to 12pter-p12. </p><p>Shelton-Inloes et al. (1987) confirmed the localization of the gene to chromosome 12 and identified a homologous sequence on chromosome 22. The VWF gene is the most distally mapped gene on 12p13.3 (NIH/CEPH Collaborative Mapping Group, 1992). </p><p>Barrow et al. (1993) showed that the loci for neurotrophin-3 (NTF3; 162660) and von Willebrand factor map to 12p13 in the human and are closely linked on mouse chromosome 6. </p><p><strong><em>Pseudogene</em></strong></p><p>
|
|
Mancuso et al. (1991) reported that the partially unprocessed pseudogene on chromosome 22q11-q13 is 21 to 29 kb long and corresponds to exons 23 to 34 of the VWF gene. They found splice site and nonsense mutations, suggesting that the pseudogene cannot yield functional transcripts. By in situ hybridization experiments on metaphase spreads from a Philadelphia-chromosome-positive chronic myelogenous leukemia (151410) patient, Patracchini et al. (1992) found that the pseudogene is located centromeric to the breakpoint cluster region. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Ruggeri (1997) reviewed VWF within a series on cell adhesion in vascular biology and took the opportunity to review the understanding of platelet function in hemostasis and thrombosis. </p><p>Sporn et al. (1987) found that the VWF released from endothelial cell Weibel-Palade bodies bound particularly avidly to the extracellular matrix. Wagner et al. (1991) showed that the VWF propolypeptide is necessary for the formation of the Weibel-Palade storage granules. Following secretagogue stimulation, Weibel-Palade bodies undergo exocytosis and release long VWF filaments, averaging 100 micrometers, that capture platelets along their length. Subsequent activation and aggregation of platelets cause the formation of a hemostatic plug (Michaux et al., 2006). Michaux et al. (2006) determined that the propeptide of VWF, which is released into the bloodstream at exocytosis, was involved in a pH-dependent interaction with the first 3 domains of mature VWF protein and this interaction was required for compact storage of VWF filaments. They showed that multimerization and tubular storage were a prerequisite for rapid unfurling of long VWF filaments in stimulated human umbilical vein endothelial cells in culture and in laser-injured cremaster venules in mice. If tubules were disassembled prior to exocytosis, short or tangled filaments were released and platelet recruitment was reduced. Michaux et al. (2006) concluded that compaction of VWF into tubules determines the rod-like shape of Weibel-Palade bodies and is critical to the protein's hemostatic function. </p><p>ADAMTS13 (604134) specifically cleaves a peptidyl bond between tyr1605 and met1606 in the A2 domain of VWF and thus acts to regulate VWF size. Kokame et al. (2004) identified a 73-amino acid peptide, which they designated VWF73, as the minimal VWF substrate cleavable by ADAMTS13. VWF73 contains asp1596 to arg1668 of VWF. </p><p>Wu et al. (2006) cleaved VWF73 into shorter peptides and found that a 24-amino acid peptide encompassing pro1645 to lys1668 was the shortest peptide that could bind ADAMTS13 and competitively inhibit its cleavage of a VWF-derived substrate. This peptide and longer peptides containing this core sequence also inhibited cleavage of multimeric VWF by ADAMTS13. These results suggested the presence of a complementary extended binding site, or exosite, on ADAMTS13. Asp1653-to-ala and asp1663-to-ala mutations in the VWF-derived substrate significantly reduced the rate of cleavage of the substrate peptide by ADAMTS13, whereas a glu1655-to-ala mutation significantly enhanced the rate of cleavage. Wu et al. (2006) concluded that ionic interactions between the exosite on ADAMTS13 and a region of VWF spanning pro1645 to lys1668 play a significant role in substrate recognition. </p><p>Cao et al. (2008) showed that, under shear stress and at physiologic pH and ionic strength, coagulation factor VIII (F8; 300841) accelerated, by a factor of about 10, the rate of ADAMTS13-mediated cleavage of the tyr1605/met1606 bond in VWF. Multimer analysis revealed that factor VIII preferentially accelerated the cleavage of high molecular weight (HMW) multimers. The ability of factor VIII to enhance VWF cleavage by ADAMTS13 was rapidly lost after pretreatment of factor VIII with thrombin (F2; 176930). Cao et al. (2008) concluded that factor VIII regulates proteolytic processing of VWF by ADAMTS13 under shear stress, which depends on the high-affinity interaction between factor VIII and VWF. </p><p>Using recombinant variants of ADAMTS13 and VWF for kinetic analysis, Gao et al. (2008) determined that segments between gln1624 and arg1668 in the VWF A2 domain interacted with the first thrombospondin-1 (see 188060) domain, the cys-rich domain, and the spacer domain of ADAMTS13. The individual interactions were relatively weak, but together they increased the rate of substrate cleavage. Internal deletion of gln1624 to arg1641 in the VWF A2 domain did not affect the cleavage rate, but short deletions on either side of the tyr1605-met1606 cleavage site abolished cleavage. Adding residues N-terminal to glu1554 in VWF reduced the rate of VWF cleavage by ADAMTS13. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
Huizinga et al. (2002) presented the crystal structure of the platelet receptor glycoprotein 1B-alpha (GP1BA; 606672) amino-terminal domain and its complex with the VWF domain A1. In the complex, GP1BA wraps around one side of A1, providing 2 contact areas bridged by an area of solvated charge interaction. The structures explain the effects of gain-of-function mutations related to bleeding disorders and provide a model for shear-induced activation. </p><p>Zhou et al. (2011) determined the crystal structure of an engineered VWF A2 domain. The structure contained a Ca(2+)-binding site in the region (residues 1591 to 1602) connecting alpha-3 to beta-4. Mutation of asp1596 or asn1602 impaired the ability of the A2 domain to bind Ca(2+). Ca(2+) binding stabilized the A2 domain and impeded unfolding of the A2 domain, thereby protecting it from cleavage by ADAMTS13. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Sadler and Ginsburg (1993) reported on a database of polymorphisms in the VWF gene and pseudogene; Ginsburg and Sadler (1993) reported on a database of point mutations, insertions, and deletions. </p><p><strong><em>Von Willebrand Disease Type 1</em></strong></p><p>
|
|
Eikenboom et al. (1996) described a family in the Netherlands in which 3 affected members with type 1 von Willebrand disease (193400) and VWF levels 10 to 15% of normal were heterozygous for a mutation in the VWF gene (C1149R; 613160.0028) The mutation resulted in a decrease in the secretion of coexpressed normal VWF, and the mutation was proposed to cause intracellular retention of pro-VWF heterodimers. </p><p>In affected members of 7 Italian families and in 1 German patient with von Willebrand disease 'Vicenza,' Schneppenheim et al. (2000) identified a heterozygous R1205H mutation in the VWF gene (613160.0027). Haplotype identity, with minor deviations in 1 Italian family, suggested a common but not very recent genetic origin of R1205H. The phenotype was characterized by these groups as showing autosomal dominant inheritance and low levels of VWF antigen in the presence of high molecular weight and ultra high molecular weight multimers, so-called 'supranormal' multimers, similar to those seen in normal plasma after infusion of desmopressin. </p><p><strong><em>Von Willebrand Disease Type 2</em></strong></p><p>
|
|
In a patient with type 2 von Willebrand disease (613554), Bernardi et al. (1990) identified a heterozygous de novo deletion of a portion of the VWF gene containing at least codons 1147 through 1854. The VWF antigen (VWF:Ag) levels were one-fourth of normal, and ristocetin cofactor (VWF:RCo) activity was severely impaired. VWF morphology showed a reduction of high molecular weight multimers in plasma and platelets, consistent with type 2A VWD. </p><p>Iannuzzi et al. (1991) identified a heterozygous mutation in the VWF gene (613160.0001) in a patient with von Willebrand disease type 2A, which is characterized by a qualitative defect in VWF, resulting in the absence of large and intermediate VWF multimers, which may be caused by increased VWF proteolysis. </p><p>In 2 families with VWD, 1 with type 2B and another with type 1, Eikenboom et al. (1994) identified multiple consecutive nucleotide changes in the 5-prime end of exon 28 that resulted in sequences identical to the VWF pseudogene, although they were demonstrated to be in the active gene. Eikenboom et al. (1994) hypothesized that each of these multiple substitutions arose from a recombination event between the gene and pseudogene, rather than from single mutation events. The findings thus represented interchromosomal gene conversion involving chromosomes 12 and 22. </p><p>In affected members of 2 unrelated families with VWD type 2CB (see 613554), Riddell et al. (2009) identified 2 different heterozygous mutations in the collagen-binding A3 domain of the VWF gene (W1745C; 613160.0040 and S1783A; 613160.0042, respectively). The patients had clinically significant bleeding episodes. Laboratory studies showed normal values of VWF:RCo to VWF:Ag (RCo:Ag), normal VWF multimer analysis, and normal ristocetin-induced platelet aggregation, but markedly reduced ratios of VWF collagen-binding activity to VWF antigen (CB:Ag) against type III collagen and type I collagen. Treatment with DDAVP resulted in a good functional response with a rise in VWF:CB resulting from an overall increase in the amount of circulating VWF, even though the qualitative defect in collagen binding remained. These findings and in vitro expression studies indicated that these mutant proteins caused a specific defect in collagen binding, which Riddell et al. (2009) suggested represented a novel classification subtype termed 'VWF 2CB.' </p><p>A decreased VWF:RCo/VWF:Ag ratio implies a VWD type 2M defect that is characterized by decreased VWF-platelet interactions in the presence of normal multimer structure. Based on laboratory findings, Flood et al. (2010) observed an overrepresentation of VWD type 2M in African American individuals (80%) compared to Caucasians (30%), among all those categorized as having VWD type 2. In addition, most of the African American individuals had minimal bleeding symptoms despite a significantly reduced VWF:RCo/VWF:Ag ratio. Genetic analysis of 59 African American and 113 Caucasian controls identified a nonsynonymous SNP (asp1472-to-his; D1472H; rs1800383) in exon 28 in the A1 domain of the VWF gene that could fully explain the lower VWF:RCo/VWF:Ag ratios in African Americans (0.81) compared to Caucasians (0.94). Whereas 63% of the African Americans were positive for D1472H, only 17% of Caucasians had this SNP. Further analysis showed that the VWF 1472H allele fully accounted for the variation in VWF:RCo/VWF:Ag independent of race. In vitro studies showed that the D1472H substitution had no effect on VWF binding to platelet GP1BA in assays that did not use ristocetin, and did not alter VWF binding to collagen. Therefore, the VWF D1472H polymorphism causes substantial variation in VWF:RCo without altering the hemostatic function of VWF in vivo. Flood et al. (2010) concluded that polymorphisms in this region may affect the measurement of VWF activity by the ristocetin assay and may not reflect a functional defect or true hemorrhagic risk. </p><p>Schneppenheim et al. (2010) reported a high frequency (29%) of VWD type 2A subtype IIE among patients with type 2A studied in their laboratory. Subtype IIE is associated with a reduction of high molecular weight (HMW) VWF multimers and a lack of outer proteolytic bands on gel electrophoresis, indicating reduced proteolysis. Genetic analysis of 38 such index cases identified 22 different mutations in the VWF gene, most of them affecting cysteine residues clustered in the D3 domain. The most common mutation was Y1146C (613160.0039), which was found in 12 (32%) probands. In vitro expression studies indicated that the Y1146C-mutant protein caused a severe reduction in or lack of HMW monomers and decreased secreted VWF antigen levels. However, clinical symptoms were heterogeneous among carriers, ranging from mild to severe bleeding. Schneppenheim et al. (2010) suggested that several mechanisms likely act in concert to produce subtype IIE, including decreased secretion of VWF, the change of a cysteine residue which may impact multimerization, and decreased half-life of the mutant protein. Altered ADAMTS13-mediated proteolysis did not appear to be a major primary factor. </p><p><strong><em>Von Willebrand Disease Type 3</em></strong></p><p>
|
|
In a patient with severe type 3 von Willebrand disease (277480), Peake et al. (1990) found a homozygous 2.3-kb deletion in the VWF gene which included exon 42; a novel 182-bp insert was found between the breakpoints. The patient had an alloantibody inhibitor to VWF. The insert was detected by PCR amplification both in the patient's DNA and in his carrier relatives. </p><p>In patients with VWD type 3, Zhang et al. (1992, 1992, 1992) identified homozygous or compound heterozygous mutations in the VWF gene (see, e.g., 613160.0015-613160.0017). Some heterozygous family members had a less severe phenotype, consistent with VWD type 1. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Denis et al. (1998) generated a mouse model for von Willebrand disease by using gene targeting. VWF-deficient mice appeared normal at birth; they were viable and fertile. Neither von Willebrand factor nor VWF-propolypeptide (von Willebrand antigen II) was detectable in plasma, platelets, or endothelial cells of the homozygous mutant mice. The mutant mice exhibited defects in hemostasis with a highly prolonged bleeding time and spontaneous bleeding events in approximately 10% of neonates. As in the human disease, the factor VIII level in these mice was reduced strongly as a result of the lack of protection provided by von Willebrand factor. Defective thrombosis in mutant mice was also evident in an in vivo model of vascular injury. In this model, the exteriorized mesentery was superfused with ferric chloride and the accumulation of fluorescently labeled platelets was observed by intravascular microscopy. Denis et al. (1998) concluded that these mice very closely mimic severe human von Willebrand disease. </p><p>Golder et al. (2010) generated transgenic mouse models of VWD type 2B by introducing mutations R1306W (613160.0005), V1316M (613160.0007), and R1341Q (613160.0008) into the murine Vwf gene. The mutant Vwf proteins were expressed by the liver and only present in the plasma compartment, not in platelets. Mutant mice showed variable thrombocytopenia, which was most severe in V1316M mice. Blood smears from mutant mice showed many platelet aggregates, which were not seen in wildtype mice, and plasma samples from mutant mice showed decreased numbers of Vwf multimers resulting from increased Adamts13-mediated proteolysis. Mice with the V1316M mutation also had large platelets. Even though the enhanced affinity of Vwf 2B mutant proteins to platelets could theoretically have a thrombotic effect, ferric chloride-induced injury to cremaster arterioles in mutant mice showed a marked reduction in thrombus development and platelet adhesion in the presence of circulating Vwf 2B. </p><p>Rayes et al. (2010) also generated mouse models of VWD type 2B by introducing the R1306Q and V1316M mutations in the murine Vwf gene. Both mutant proteins were associated with enhanced ristocetin-induced platelet aggregation, and mutant mice developed thrombocytopenia and circulating platelet aggregates, both of which were more pronounced for mice with the V1316M mutation. Only the V1316M mutant showed spontaneous platelet aggregation in vitro. Blood smears from mutant mice showed increased platelet size compared to wildtype. Both mutant proteins had a 2- to 3-fold reduced half-life and induced a 3- to 6-fold increase in number of giant platelets compared with wild-type Vwf. Loss of large multimers was observed in 50% of mutant mice. In vivo hemostatic potential of both mutants was severely impaired, even in an thrombotic model of arterial vessel occlusion. Mice who were doubly mutant for Vwf 2B and Adamts13 deficiency had more and larger circulating platelet aggregates and did not lack high molecular weight (HMW) multimers. The findings confirmed that VWD type 2B is dependent upon the type of mutation and pointed to an important role for ADAMTS13 in modulating platelet size as well as the removal of HMW VWF. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>42 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, ILE1628THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61750584,
|
|
|
|
|
|
|
|
ClinVar: RCV000000308, RCV000086808, RCV000778377, RCV002243602, RCV004739270
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated ILE865THR is now designated ILE1628THR (I1628T). </p><p>In affected members of a family with von Willebrand disease type 2A (see 613554), Iannuzzi et al. (1991) identified a 4883T-C transition in the VWF gene, resulting in an ile865-to-thr (I865T) substitution. Type 2A VWD is characterized by a qualitative defect in VWF, resulting in the absence of large and intermediate VWF multimers, which may be caused by increased VWF proteolysis. The I865T substitution was located immediately adjacent to 2 other previously identified mutations that also result in type 2A von Willebrand disease (R834W, 613160.0002 and V844D, 613160.0003), suggesting a clustering for these mutations in a portion of the protein critical for proteolysis. </p><p>Dent et al. (1990) noted that the I865T, R834W, and V844D mutations are located within a 32-amino acid segment in the midportion of the 2,813-amino acid VWF coding sequence. Type IIA von Willebrand disease is characterized by normal or only moderately decreased levels of von Willebrand factor, the absence of large and intermediate VWF multimers, and increased VWF proteolysis with an increase in the plasma levels of the 176-kD VWF proteolytic fragment. The proteolytic cleavage site is located between tyr842 and met843. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, ARG1597TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61750117,
|
|
|
|
|
|
gnomAD: rs61750117,
|
|
|
|
|
|
ClinVar: RCV000000309, RCV000086797, RCV000623564, RCV000851942, RCV000999877, RCV002243603
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated ARG834TRP is now designated ARG1597TRP (R1597W). </p><p>In a patient with von Willebrand disease type 2A (see 613554), characterized by selective loss of high molecular weight VWF multimers, Ginsburg et al. (1989) identified a heterozygous 4789C-T transition in the VWF gene, resulting in an arg834-to-trp (R834W) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, VAL1607ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61750579,
|
|
|
|
|
|
|
|
ClinVar: RCV000000310, RCV000086803, RCV002243604
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated VAL844ASP is now designated VAL1607ASP (V1607D). </p><p>In a patient with von Willebrand disease type 2A (see 613554), characterized by selective loss of high molecular weight VWF multimers, Ginsburg et al. (1989) identified a heterozygous 4820T-A transversion in the VWF gene, resulting in a val844-to-asp (V844D) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 VON WILLEBRAND DISEASE, TYPE 2B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, TRP1313CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61749392,
|
|
|
|
|
|
|
|
ClinVar: RCV000000311, RCV000086709
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated TRP550CYS is now designated TRP1313CYS (W1313C). </p><p>In the patient identified as case 7 in the report by Kyrle et al. (1988) with laboratory findings consistent with the diagnosis of type 2B von Willebrand disease (see 613554), Ware et al. (1991) found a trp550-to-cys (W550C) substitution. The mutation is located in the domain of the molecule comprising residues 449 to 728 involved in the binding to platelet glycoprotein Ib-IX receptor complex (see 606672). This interaction is physiologically regulated so that it does not occur between circulating VWF and platelets but, rather, only at a site of vascular injury. The abnormal VWF found in type 2B von Willebrand disease has a characteristically increased affinity for GP Ib and binds to the circulating platelets. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 VON WILLEBRAND DISEASE, TYPE 2B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, ARG1306TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61749384,
|
|
|
|
|
|
|
|
ClinVar: RCV000000312, RCV000086699, RCV000851599, RCV000851989, RCV000851990, RCV005007800
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated ARG543TRP is now designated ARG1306TRP (R1306W). </p><p>In 2 unrelated patients with VWD type 2B (see 613554), Randi et al. (1991) identified a heterozygous 4166C-T transition in exon 28 of the VWF gene, resulting in an arg543-to-trp (R543W) substitution in the domain that interacts with platelet glycoprotein GP1BA (606672). Both patients had previously been reported by Ruggeri et al. (1980) as having VWD with a heightened interaction between platelets and VWF. Patient plasma showed a decrease in large VWF multimers due to spontaneous binding of VWF to platelets and subsequent clearance from the circulation. </p><p>Donner et al. (1992) studied 20 patients from 9 unrelated families with type 2B VWD from Denmark, Germany, and Sweden. Fifteen patients in 5 families were heterozygous for the R543W mutation. In 2 of the 5 families, it represented a de novo mutation. In one of the other families, the father, though asymptomatic and with normal laboratory test results, carried the mutation in heterozygous form. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 VON WILLEBRAND DISEASE, TYPE 2B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, ARG1308CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61749387,
|
|
|
|
|
|
|
|
ClinVar: RCV000000313, RCV000086703, RCV000851770, RCV002225253
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated ARG545CYS is now designated ARG1308CYS (R1308C). </p><p>In 7 patients from 4 unrelated families with VWD type 2B (see 613554), Randi et al. (1991) identified a heterozygous 4172C-T transition in exon 28 of the VWF gene, resulting in an arg545-to-cys (R545C) substitution in the domain that interacts with platelet glycoprotein GP1BA (606672). Patient plasma showed a decrease in large VWF multimers due to spontaneous binding of VWF to platelets and subsequent clearance from the circulation. Examination of the RFLP haplotype background for the R545C mutations identified in their study permitted Randi et al. (1991) to conclude that the mutation had occurred independently 3 times; a fourth patient represented a new mutation. </p><p>Donner et al. (1991) reported another family with this mutation. In a later study of 20 patients from 9 unrelated families with type 2B VWD from Denmark, Germany, and Sweden, Donner et al. (1992) found the arg545-to-cys mutation in heterozygous state in 4 affected persons in 3 families. </p><p>In a Japanese patient with VWD type 2B, Hagiwara et al. (1996) identified a homozygous mutation in exon 28 of the VWF gene, resulting in an arg1308-to-cys (R1308C) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 VON WILLEBRAND DISEASE, TYPE 2B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, VAL1316MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61749397,
|
|
|
|
|
|
gnomAD: rs61749397,
|
|
|
|
|
|
ClinVar: RCV000000314, RCV000086715, RCV000507168, RCV000678767, RCV000851771, RCV002476901
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated VAL553MET is now designated VAL1316MET (V1316M). </p><p>In a patient with VWD type 2B (see 613554), Randi et al. (1991) identified a heterozygous 4196G-A transition in exon 28 of the VWF gene, resulting in a val553-to-met (V553M) substitution in the domain that interacts with platelet glycoprotein GP1BA (606672). Patient plasma showed a decrease in large VWF multimers due to spontaneous binding of VWF to platelets and subsequent clearance from the circulation. </p><p>Murray et al. (1992) also observed this mutation in multiple members of a family with type 2B von Willebrand disease. They showed by VWF polymorphism analysis that the mutation originated in a VWF gene transmitted from a phenotypically normal grandfather. Analysis of the sperm from this individual showed that approximately 5% of the germline contained the mutant sequence. </p><p>Jackson et al. (2009) identified a heterozygous V1316M substitution in affected members of a large French Canadian family with VWD type 2B that was described by Milton et al. (1984) as having the 'Montreal platelet syndrome.' Affected individuals had lifelong bruising; some patients had severe postoperative bleeding, postpartum hemorrhage, and gastrointestinal bleeding. A significant proportion of platelets occurred in microaggregates typically containing 2 to 6 platelets, and the aggregation could be increased by stirring. Affected family members had macrothrombocytopenia, borderline to normal VWF antigen, low ristocetin cofactor activity, and normal factor VIII coagulant activity, all consistent with VWD type 2B. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 VON WILLEBRAND DISEASE, TYPE 2B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, ARG1341GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61749403,
|
|
|
|
|
|
gnomAD: rs61749403,
|
|
|
|
|
|
ClinVar: RCV000000315, RCV000086721, RCV002227435, RCV002243605, RCV004547443
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated ARG578GLN is now designated ARG1341GLN (R1341Q). </p><p>In a patient with VWD type 2B (see 613554), Cooney et al. (1991) identified a heterozygous 4022G-A transition in the VWF gene, resulting in an arg578-to-gln (R578Q) substitution within the putative GP1BA (606672)-binding domain. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, SER1613PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61750581,
|
|
|
|
|
|
|
|
ClinVar: RCV000000316, RCV000086805
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated SER850PRO is now designated SER1613PRO (S1613P). </p><p>Randi et al. (1991) suggested that mutations causing type IIA von Willebrand disease are clustered in the A2 domain of the VWF gene. The ser850-to-pro (S850P) mutation, designated S1613P based on a different numbering system, is in the A2 region of the gene (Goodeve, 2010). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 VWF POLYMORPHISM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, ARG1399HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1800382,
|
|
|
|
|
|
gnomAD: rs1800382,
|
|
|
|
|
|
ClinVar: RCV000756907, RCV000851940, RCV001270629, RCV002243606, RCV003234883, RCV003447466, RCV004547444
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the polymorphism originally designated ARG636HIS is now designated ARG1399HIS (R1399H). </p><p>Cooney et al. (1991) found a rare sequence polymorphism at nucleotide 4196 of the VWF gene. A 4196G-A transition led to an arg636-to-his (R636H) substitution. The allele frequency was estimated to be about 0.015. Although the change was within the region involved in binding to platelet glycoprotein receptor and the region mutant in von Willebrand disease type 2B (see 613554), no hematologic abnormality was associated with the change. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 VON WILLEBRAND DISEASE, TYPE 2N</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, THR791MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61748477,
|
|
|
|
|
|
gnomAD: rs61748477,
|
|
|
|
|
|
ClinVar: RCV000000318, RCV000086606, RCV000851745, RCV002227436, RCV002264633
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated THR28MET is now designated THR791MET (T791M). </p><p>In a 50-year-old French woman, born of consanguineous parents, with the Normandy type of VWD (VWD2N; see 613554) reported by Mazurier et al. (1990), Gaucher et al. (1991) identified a homozygous 791C-T transition in exon 18 of the VWF gene, resulting in a thr28-to-met (T28M) substitution in the mature VWF subunit. The woman had a lifelong history of excessive bleeding, and laboratory data showed decreased factor VIII (300841), subnormal bleeding time, and normal VWF multimers. VWF isolated from patient plasma was unable to bind factor VIII. Gaucher et al. (1991) noted that the phenotype resembled hemophilia A, or F8 deficiency, but showed autosomal recessive instead of X-linked inheritance. </p><p>By functional expression studies, Tuley et al. (1991) showed that the T28M mutation occurred in the factor VIII binding site of the VWF molecule. The corresponding mutant recombinant molecule formed normal multimers and had normal ristocetin cofactor activity, but had a defect in factor VIII binding. </p><p>Wise et al. (1993) reported a family with VWD type 2N ascertained through a female patient with low levels of factor VIII activity. The patient was homozygous for the thr28-to-met mutation, which was heterozygous in both parents. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 VON WILLEBRAND DISEASE, TYPE 2N</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, ARG816TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121964894,
|
|
|
|
|
|
gnomAD: rs121964894,
|
|
|
|
|
|
ClinVar: RCV000000319, RCV000086613, RCV001195286, RCV004795363
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated ARG53TRP is now designated ARG816TRP (R816W). </p><p>In a family with the Normandy type of von Willebrand disease (VWD2N; see 613554), Gaucher et al. (1991) demonstrated homozygosity for a C-to-T transition resulting in an arg53-to-trp (R53W) substitution in the mature protein. Although there was no known parental consanguinity, both parents originated from the same village in Portugal. The 2 alleles showed sequence variation within the intron 40 VNTR and might have arisen after the arg53-to-trp mutation occurred. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 VON WILLEBRAND DISEASE, TYPE 2N</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
VON WILLEBRAND DISEASE, TYPE 1, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, ARG854GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs41276738,
|
|
|
|
|
|
gnomAD: rs41276738,
|
|
|
|
|
|
ClinVar: RCV000000320, RCV000000321, RCV000086620, RCV000169683, RCV000336497, RCV000762901, RCV000851593, RCV001270529, RCV003987302, RCV004547445, RCV004771452
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated ARG91GLN is now designated ARG854GLN (R854Q). </p><p>In a patient with the Normandy type of von Willebrand disease (VWD2N; see 613554), Gaucher et al. (1991) demonstrated compound heterozygosity for the arg53-to-trp mutation (193400.0012) and another C-to-T transition that resulted in a substitution of glutamine for arginine-91. The patient's parents were related as second cousins. </p><p>Hilbert et al. (2004) reported 2 unrelated French patients with type 2N VWD who were compound heterozygous for R854Q and another pathogenic mutation (Y795C, 613160.0031 and C804F, 613160.0032, respectively). </p><p>Peerlinck et al. (1992) identified a heterozygous A-to-G transition in exon 20 of the VWF gene, resulting in an arg854-to-gln (R854Q) substitution, in a 23-year-old woman with a lifelong history of bleeding and low VWF levels, consistent with von Willebrand disease type 1 (193400). Laboratory studies showed disproportionately low factor VIII (F8; 300841) and decreased binding capacity of VWF for F8. The R854Q substitution occurred in the putative factor VIII-binding domain. All VWF multimers were normal. Neither parent was clinically affected, but laboratory studies showed that the father had partially increased bleeding time and partially decreased VWF antigen. Restriction enzyme analysis indicated that the unaffected mother was also heterozygous for the R854Q mutation, and that the patient had inherited a hypomorphic 'silent' VWF allele from her father. Peerlinck et al. (1992) noted that the inheritance pattern in this family was difficult to determine, but concluded that the presence of the 'silent' allele allowed the clinical expression of the mutated second allele, resulting in a recessive phenotype in the proband. Peerlinck et al. (1992) commented that although the phenotype was similar to that of the 'Normandy' type 2N variant (see 613554), the patient also had quantitatively low VWF and was thus classified as having VWD type 1. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-text-font">
|
|
<strong>.0014 MOVED TO 613160.0013</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 VON WILLEBRAND DISEASE, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
VON WILLEBRAND DISEASE, TYPE 1, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, ARG1659TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61750595,
|
|
|
|
|
|
gnomAD: rs61750595,
|
|
|
|
|
|
ClinVar: RCV000000322, RCV000000323, RCV000086820, RCV002227437, RCV004739271
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with von Willebrand disease type 3 (277480), Zhang et al. (1992) identified a homozygous C-to-T transition in exon 28 of the VWF gene, resulting in an arg1659-to-ter (R1659X) substitution. Both parents carried the heterozygous mutation; the clinical features of the family were not reported. </p><p>Zhang et al. (1992) identified the R1659X mutation in affected members of 3 families from western Finland with VWD type 3. Severely affected individuals were either homozygous or presumed to be compound heterozygous with another pathogenic mutation. In 1 family, heterozygous mutation carriers had a less severe phenotype, consistent with type 1 VWD (193400). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 VON WILLEBRAND DISEASE, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
VON WILLEBRAND DISEASE, TYPE 1, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, ARG1852TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61750612,
|
|
|
|
|
|
gnomAD: rs61750612,
|
|
|
|
|
|
ClinVar: RCV000000324, RCV000000325, RCV000086843, RCV000851820, RCV001813924, RCV003447467, RCV004547446
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Swedish patient with VWD type 3 (277480) and pronounced bleeding tendency, Zhang et al. (1992) identified homozygous C-to-T transition in exon 32 of the VWF gene, resulting in an arg1852-to-ter (R1852X) substitution. Two additional Swedish patients with type 3 were heterozygous for the mutation, but were predicted to be compound heterozygous for another mutation because their phenotype was more severe than other family members, who had type 1 disease (193400). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 VON WILLEBRAND DISEASE, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, ARG2635TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61751296,
|
|
|
|
|
|
gnomAD: rs61751296,
|
|
|
|
|
|
ClinVar: RCV000000326, RCV000086892, RCV002227438, RCV002264634
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with severe VMD type 3 (277480), Zhang et al. (1992) identified a C-to-T transition in exon 45 of the VWF gene, resulting in an arg2635-to-ter (R2635X) substitution. Although the patient was heterozygous for this mutation, he was thought to be a compound heterozygote for another, as yet unidentified mutation, since he had severe disease. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 VON WILLEBRAND DISEASE, TYPE 2M</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, GLY1324SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61749398,
|
|
|
|
|
|
gnomAD: rs61749398,
|
|
|
|
|
|
ClinVar: RCV000000327, RCV000086716, RCV003447468
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated GLY561SER is now designated GLY1324SER (G1324S). </p><p>In a patient with VWD type 2M (see 613554), Rabinowitz et al. (1992) identified a heterozygous mutation in exon 28 of the VWF gene, resulting in a gly561-to-ser (G561S) substitution within the GP1BA (606672)-binding domain of the mature protein. Laboratory studies of patient plasma showed normal botrocetin-induced binding but no ristocetin-induced binding to platelet glycoprotein Ib. The patient's plasma VWF contained a full range of multimers. The mutant recombinant protein formed normal multimers, but exhibited the same functional defect as the patient's plasma VWF. The patient was originally described by Howard et al. (1984) and Andrews et al. (1989). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, CYS1272ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61749372,
|
|
|
|
|
|
|
|
ClinVar: RCV000000328, RCV000086679, RCV002243607
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated CYS509ARG is now designated CYS1272ARG (C1272R). </p><p>In a patient with type 2A von Willebrand disease (see 613554), Lavergne et al. (1992) found a 3814T-C transition in the 5-prime end of exon 28 of the VWF gene, resulting in a cys509-to-arg (C509R) substitution. This mutation eliminated an intramolecular disulfide bridge formed by cys509 and cys695. The bridge is important to maintenance of the configuration of VWF functional domains that interact with platelet glycoprotein Ib-IX. However, it appeared that this bridge also affects the processing and composition of VWF multimers, since the patient had a type 2A phenotype. The amino acid substitution was the result of a 381T-C transition. The findings suggested a broader pathogenic mechanism for VWF type 2A. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 VON WILLEBRAND DISEASE, TYPE 2B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, VAL1314LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61749393,
|
|
|
|
|
|
|
|
ClinVar: RCV000000329, RCV000087017
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated VAL551LEU is now designated VAL1314LEU (V1314L). </p><p>In 1 of 20 patients from 9 unrelated families with type 2B VWD (see 613554) from Denmark, Germany, and Sweden, Donner et al. (1992) found heterozygosity for a de novo val551-to-leu (V551L) mutation. In most of the patients with type 2B VWD, spontaneous thrombocytopenia had been recorded on at least one occasion. The patient with the val551-to-leu substitution and 5 patients with the arg543-to-trp (613160.0005) substitution had had bleeding associated with thrombocytopenia in the neonatal period or early infancy. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 VON WILLEBRAND DISEASE, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, 1-BP DEL, EX18, C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs62643632,
|
|
|
|
|
|
gnomAD: rs62643632,
|
|
|
|
|
|
ClinVar: RCV000000330, RCV000086611, RCV000851752, RCV000852083, RCV002264635, RCV002476902, RCV005000978
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Among 24 patients with von Willebrand disease type 3 (277480), Zhang et al. (1992) found that 24 of the 48 chromosomes harbored a 1-bp deletion in a stretch of 6 cytosines at position 2679-2684 in exon 18 of the VWF gene. Nine patients were homozygous and 6 were heterozygous for the mutation. The deletion interrupted the reading frame and resulted in a translational stop codon at position V842 in the amino acid sequence. Translation of the mutant mRNA would yield only a severely truncated mature VWF (48 of 2,050 amino acids) after removal of the propeptide. </p><p>Zhang et al. (1993) demonstrated that deletion of 1 cytosine in exon 18 was the mutation in the Aland family (family S) in which the disease was first reported by von Willebrand (1926). They reported studies of descendants of the original family; only heterozygotes were found surviving. The proposita was a 5-year-old girl, who later bled to death during her fourth menstrual period. She had a normal coagulation time, but the bleeding time was prolonged, despite a normal platelet count. All but 1 of her 11 sibs had bleeding symptoms, as did both of her parents, who were third cousins, and many members of her family on both sides. Four of the proband's sisters had died of uncontrolled bleeding in early childhood; 3 died from gastrointestinal bleeding and 1 from bleeding after she bit her tongue in a fall. The predominant symptoms were bleeding from mucous membranes, such as from the nose, the gingivae after tooth extractions, the uterus, and the gastrointestinal tract. In contrast to hemophilia, hemarthroses seemed to be rare. All 5 of the girls who died from uncontrolled bleeding were probably homozygous for the deletion. </p><p>Mertes et al. (1993) found that the single cytosine deletion in exon 18 observed in half the alleles of 24 Swedish VWD type 3 patients (Zhang et al., 1992) occurred uncommonly in German patients with type 3 VWD; only 1 out of 24 alleles carried the delta-C mutation. A founder effect might explain the higher frequency in Sweden. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, PHE1514CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61750101,
|
|
|
|
|
|
|
|
ClinVar: RCV000000331, RCV000086775
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated PHE751CYS is now designated PHE1514CYS (F1514C). </p><p>In 8 patients from a large type 2A (see 613554) von Willebrand disease family, Gaucher et al. (1993) found a heterozygous T-to-G transversion resulting in a phe751-to-cys (F751C) substitution in the mature subunit. Type 2A is a variant form of von Willebrand disease characterized by the absence of high molecular weight VWF multimers in plasma. Gaucher et al. (1993) noted that most of the candidate missense mutations potentially responsible for type 2A VWD have been found clustered within a short segment of VWF, lying between gly742 and glu875 of the mature subunit. Gaucher et al. (1993) suggested that the mutation may induce a conformational change of the VWF subunit affecting either its sensitivity to proteolytic cleavage or, more likely, its intracellular transport as suggested by the abnormal multimeric pattern of platelet VWF observed in these patients. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, GLY550ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61754011,
|
|
|
|
|
|
|
|
ClinVar: RCV000000332, RCV000086570
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a German woman with von Willebrand disease type 2 (613554), referred to as type IIC, Schneppenheim et al. (1995) identified a homozygous 1898G-A transition in exon 14 of the VWF gene, resulting in a gly550-to-arg (G550R) substitution in the D2 domain. The proband had frequent epistaxis, easy bruising, and menorrhagia, and laboratory studies showed decreased VWF activity and decreased levels of high molecular weight multimers. The subtype of VWD was originally referred to as 'type IIC,' which shows recessive inheritance and an altered multimer pattern. Further family members were heterozygous for the mutation and were phenotypically normal or only mildly affected, in accordance with the recessive pattern of inheritance. </p><p>Sadler et al. (2006) stated that the subtype previously known as VWD IIC is due to mutations in the VWF propeptide that prevent multimerization of VWF in the Golgi apparatus. This form is now referred to as VWD type 2A. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, CYS2773ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61751310,
|
|
|
|
|
|
|
|
ClinVar: RCV000000333, RCV000086917
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated CYS2010ARG is now designated CYS2773ARG (C2773R). </p><p>In 2 unrelated patients with VWD type 2 (613554), Schneppenheim et al. (1996) identified a heterozygous cys2010-to-arg (C2010R) mutation in the mature VWF protein. Recombinant expression of mutant VWF fragments demonstrated that the mutation was responsible for defective disulfide bonding of the C-terminal domains, thus impairing dimer formation. In 1 family, both alleles were normal in the parents and 1 sister; thus, the mutation originated de novo in the proposita. The phenotype of what was then called type IID von Willebrand disease includes autosomal dominant inheritance of a moderate to severe hemorrhagic diathesis, prolonged bleeding time, normal factor VIII procoagulant and VWF antigen levels, but markedly reduced ristocetin cofactor activity due to the lack of large VWF multimers in plasma. </p><p>Sadler et al. (2006) stated that the subtype previously known as VWD IID is due to heterozygous mutations in the C-terminal domain of VWF that prevent VWF dimerization in the endoplasmic reticulum. This form is now referred to as VWD type 2A. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-text-font">
|
|
<strong>.0025 MOVED TO 613160.0006</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, 6-BP INS, NT1212
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61754006,
|
|
|
|
|
|
|
|
ClinVar: RCV000086561, RCV002271405
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Holmberg et al. (1998) found that a patient with type 2 VWD (613554) reported by Ruggeri et al. (1982) was compound heterozygous for 2 mutations in the VWF gene: a null mutation and a 6-nucleotide insertion, 1212ins6 (AATCCC), in exon 11, predicting the insertion of the amino acids asparagine and proline between phenylalanine-404 and threonine-405 of the von Willebrand propeptide. The patient was originally classified as type IIC, since laboratory studies showed absence of the high molecular weight multimers and a marked increase of the smallest multimer (the protomer) in both plasma and platelets. The IIC phenotype showed recessive inheritance. </p><p>Sadler et al. (2006) stated that the subtype previously known as VWD IIC is due to mutations in the VWF propeptide that prevent multimerization of VWF in the Golgi apparatus. This form is now referred to as VWD type 2A. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 VON WILLEBRAND DISEASE, TYPE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
VON WILLEBRAND FACTOR VICENZA
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, ARG1205HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121964895,
|
|
|
|
|
|
|
|
ClinVar: RCV000000335, RCV000000336, RCV000086666, RCV000851598, RCV001003906, RCV004547447
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>The arg1205-to-his mutation (R1205H) in the VWF gene is sometimes referred to as VWF Vicenza.</p><p>In affected members of 7 Italian families and in 1 German patient with von Willebrand disease (193400) 'Vicenza,' Schneppenheim et al. (2000) identified a heterozygous 3864G-A transition in exon 27 of the VWF gene, resulting in an R1205H substitution in the D3 domain. The mutation was not found in unaffected family members or in 100 control chromosomes. Haplotype identity, with minor deviations in 1 Italian family, suggested a common but not very recent genetic origin of R1205H. Von Willebrand disease 'Vicenza' was originally described in patients living in the region of Vicenza in Italy (Mannucci et al., 1988). Randi et al. (1993) demonstrated that the clinical disorder in Italian patients is linked to the VWF gene. A number of additional families were identified in Germany by Zieger et al. (1997). The phenotype was characterized by these groups as showing autosomal dominant inheritance and low levels of VWF antigen in the presence of high molecular weight and ultra high molecular weight multimers, so-called 'supranormal' multimers, similar to those seen in normal plasma after infusion of desmopressin. </p><p>Casonato et al. (2002) identified 4 additional families with the R1205H variant. Affected individuals showed a mild bleeding tendency and significant decrease in plasma VWF antigen and ristocetin cofactor activity, but normal platelet VWF levels. Larger than normal VWF multimers were also observed. However, VWF multimers disappeared rapidly from the circulation after desmopressin, indicating reduced survival of the mutant VWF protein. Since ristocetin-induced platelet aggregation was normal, Casonato et al. (2002) attributed the phenotype to reduced survival of normally synthesized VWF, which is consistent with type 1 VWF. </p><p>In Wales, Lester et al. (2006) investigated 7 kindreds with VWD Vicenza R1205H. All affected individuals had been diagnosed with moderate to severe type 1 VWD. Among all families with highly penetrant type 1 VWD investigated in the center, heterozygosity for the R1205H mutation was found to be the most common underlying defect. A severe laboratory phenotype associated with a bleeding history that was milder than expected was commonly observed. Lester et al. (2006) provided evidence that the R1205H mutation can arise de novo. </p><p>Cumming et al. (2006) identified the Vicenza variant in 4 (12.5%) of 32 UK patients with type 1 VWD. These authors stated that the R1205H substitution resulted from a 3614G-A transition in exon 27. The mutation was highly penetrant and consistently associated with moderate to severe type I disease. VWF multimer studies did not show the presence of ultralarge multimers in any affected individuals; the authors thus classified the Vicenza variant to be a type 1 quantitative defect, rather than a type 2M qualitative defect as had been suggested by Castaman et al. (2002). Three of the 4 families reported by Cumming et al. (2006) shared the same haplotype, suggesting a common origin of the mutation. </p><p>In a review, Sadler et al. (2006) noted that the Vicenza VWF variant has increased clearance compared to wildtype VWF. Sadler et al. (2006) also noted that the Vicenza variant has been classified as VWD type 2M due to the presence of high molecular weight multimers. However, since VWF antigen and functional activity are decreased proportionately, it is better classified as VWD type 1. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 VON WILLEBRAND DISEASE, TYPE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, CYS1149ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61748511,
|
|
|
|
|
|
|
|
ClinVar: RCV000000337, RCV000086657, RCV002264636, RCV004821258
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Eikenboom et al. (1996) described a family in the Netherlands in which 3 affected members with type 1 von Willebrand disease (193400) and VWF levels 10 to 15% of normal were heterozygous for a mutation in exon 26 of the VWF gene, resulting in a cys1149-to-arg (C1149R) substitution in the D3 domain (numbered from the initiation codon, or cys386-to-arg, numbered from the N terminus of the mature subunit). The mutation resulted in a decrease in the secretion of coexpressed normal VWF, and the mutation was proposed to cause intracellular retention of pro-VWF heterodimers. The multimer pattern remained nearly normal and consistent with a dominant VWD type 1 phenotype. </p><p>Bodo et al. (2001) performed experiments supporting the hypothesis that normal and C1149R mutant subunits formed heterodimers that, like homodimers of C1149R, were retained in the endoplasmic reticulum. Such a mechanism would explain the dominant-negative effect of the C1149R mutation on VWF secretion, and the authors suggested that a similar dominant-negative mechanism could cause quantitative deficiencies of other multisubunit proteins. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 VON WILLEBRAND DISEASE, TYPE 1, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, TYR1584CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1800386,
|
|
|
|
|
|
gnomAD: rs1800386,
|
|
|
|
|
|
ClinVar: RCV000000338, RCV000086795, RCV000622977, RCV000678772, RCV001255177, RCV001843449, RCV002280857, RCV003313770, RCV004547448, RCV004700174, RCV004795364
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>O'Brien et al. (2003) addressed the molecular basis of type 1 von Willebrand disease (193400) in a comprehensive manner through a Canadian population-based study. In 10 Canadian families and 2 families from the UK with type 1 VWD, O'Brien et al. (2003) identified a heterozygous 4751A-G transition in exon 28 of the VWF gene, resulting in a tyr1584-to-cys (Y1584C) substitution. The Y1584C variant was found in 1 of 100 controls, but this individual had low VWF antigen levels, suggesting an affected status. One study participant with the mutation had a normal VWF antigen level and no history of bleeding, suggesting incomplete penetrance, and another who was homozygous for the mutation had significantly decreased VWF antigen levels. The mutation was associated with a common haplotype in a significant portion of patients with the disorder and was in-phase with a splice site variation (5312-19A-C) in some families. In vitro functional expression studies showed that the mutation resulted in increased intracellular retention of the VWF protein, resulting in a quantitative defect. Molecular dynamic simulation on a homology model of the VWF-A2 domain containing the Y1584C mutation showed that no significant structural changes occurred as a result of the substitution, but that a new solvent-exposed reactive thiol group was apparent. </p><p>Bowen and Collins (2004) described a patient with type 1 von Willebrand disease in whom the von Willebrand factor showed increased susceptibility to proteolysis by ADAMTS13 (604134). Investigation of additional family members indicated that increased susceptibility was heritable, but it did not track uniquely with type 1 VWD. Sequence analysis showed that increased susceptibility to proteolysis tracked with the Y1584C substitution. A prospective study of 200 individuals yielded 2 Y1584C heterozygotes; for both, plasma VWF showed increased susceptibility to proteolysis. </p><p>Bowen et al. (2005) identified heterozygosity for the Y1584C variant in 19 (25%) of 76 UK patients with type 1 VWD. This corresponded to 8 (27%) of 30 total families studied. However, the Y1584C variant did not segregate with disease in 4 families: 5 unaffected individuals carried the variant, whereas 3 affected individuals did not. These findings indicated that Y1584C is not solely causative of type 1 VWD. Eighteen of the 19 patients were ABO blood group (616093) type O, suggesting there may be an interaction between C1584 and blood group O. In vitro studies of plasma showed that Y1584C VWF had increased susceptibility to proteolysis by ADAMTS13, even in those who did not have VWD. Bowen et al. (2005) proposed a mechanism in which Y1584C VWF undergoes increased proteolysis, which may increase bleeding risk in carriers. However, presence for the variant is not causative for the disorder, and may instead represent a risk factor. </p><p>Cumming et al. (2006) identified heterozygosity for the Y1584C variant in 8 (25%) of 32 UK families and in 19 (17%) of 119 related individuals with type 1 VWD. Eighteen (95%) of the 19 individuals were blood group O. Heterozygosity for Y1584C segregated with VWD in 3 families, did not segregate with VWD in 4 families, and showed equivocal results in 2 families. Cumming et al. (2006) concluded that Y1594C is a polymorphism that is frequently associated with type 1 VWD, but shows incomplete penetrance and does not consistently segregate with the disease. The association with blood group type O may be related to the fact that both blood group O and Y1584C are associated with increased proteolysis of VWF by ADAMTS13. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 VON WILLEBRAND DISEASE, TYPE 2M</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, SER1285PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61749380,
|
|
|
|
|
|
gnomAD: rs61749380,
|
|
|
|
|
|
ClinVar: RCV000000339, RCV000086691
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a French mother and son with VWD type 2M (see 613554), Stepanian et al. (2003) identified a heterozygous 3854C-T transition in exon 28 of the VWF gene, resulting in a ser1285-to-phe (S1285F) substitution in the A1 loop of the protein. In vitro functional expression studies in COS-7 cells showed that the mutant VWF had markedly reduced ristocetin-induced binding to platelets via GP1BA (606672), consistent with a loss of function. The findings indicated that the S1285F mutation altered the folding of the A1 loop and prevented the correct exposure of VWF binding sites to GP1BA. Both patients had a moderate bleeding syndrome with epistaxis and easy bruising. Laboratory studies showed mildly decreased VWF antigen levels, normal multimers, and severely decreased VWF functional activity. Factor VIII (F8; 300841) was mildly decreased and platelet counts were normal. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 VON WILLEBRAND DISEASE, TYPE 2N</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, TYR795CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61748478,
|
|
|
|
|
|
|
|
ClinVar: RCV000000340, RCV000086607
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a French patient with VWD type 2N (see 613554), Hilbert et al. (2004) identified compound heterozygosity for 2 mutations in the VWF gene: a 2384A-G transition in exon 18 resulting in a tyr795-to-cys (Y795C) substitution in the D-prime domain, and R854Q (613160.0013). In vitro functional expression assays showed that the mutant VWF protein had decreased binding to factor VIII (300841), and resulted in an abnormal multimeric pattern consistent with ultralarge multimers. Hilbert et al. (2004) suggested that the effect on the cysteine residue may alter protein conformation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0032 VON WILLEBRAND DISEASE, TYPE 2N</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, CYS804PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs62643630,
|
|
|
|
|
|
|
|
ClinVar: RCV000000341, RCV000086609
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a French patient with VWD type 2N (see 613554), Hilbert et al. (2004) identified compound heterozygosity for 2 mutations in the VWF gene: a 2411G-T transversion in exon 18 resulting in a cys804-to-phe (C804F) substitution in the D-prime domain, and R854Q (613160.0013). In vitro functional expression assays showed that the mutant VWF protein had decreased binding to factor VIII (300841), and resulted in an abnormal multimeric pattern consistent with loss of ultralarge multimers. Hilbert et al. (2004) suggested that the effect on the cysteine residue may alter protein conformation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0033 VON WILLEBRAND DISEASE, TYPE 2B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WVF, PRO1266LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61749370,
|
|
|
|
|
|
gnomAD: rs61749370,
|
|
|
|
|
|
ClinVar: RCV000000342, RCV000086676, RCV000314989, RCV000853236, RCV002247228, RCV003313771, RCV004547449
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as a reference sequence.' Thus, the mutation originally designated PRO503LEU is now designated PRO1266LEU (P1266L). </p><p>In affected members of a Swedish family (Holmberg et al., 1986) and a German family with a variant of VWD type 2B (see 613554), Holmberg et al. (1993) identified a heterozygous C-to-T transition in the VWF gene, resulting in a pro503-to-leu (P503L) substitution in the mature subunit. The phenotype was unique in that there was a mild bleeding disorder, and laboratory studies showed that platelets aggregated at much lower ristocetin concentrations than normal. The bleeding time was variously prolonged, and VWF:Ag, VWF activity, and F8 were decreased. All VWF multimers were present, and there was no thrombocytopenia. The defect in this family, inherited as an autosomal dominant trait, resembled that of type 2B because of the response to ristocetin, but differed because all VWF multimers were present. Holmberg et al. (1986) referred to it as 'type 2 Malmo.' Weiss and Sussman (1985) reported a similarly affected family, and referred to this variant as 'type I New York' (Sadler et al., 2006). Wylie et al. (1988) also described this variant and noted that there was no spontaneous aggregation of platelets. </p><p>Sadler et al. (2006) emphasized that this variant is a form of VWD type 2B with increased sensitivity to ristocetin in vivo. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0034 VON WILLEBRAND DISEASE, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, CYS2362PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61750630,
|
|
|
|
|
|
|
|
ClinVar: RCV000000343, RCV000086870
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In several patients from northern Italy with VWD type 3 (277480), Eikenboom et al. (1998) identified a homozygous mutation in the VWF gene, resulting in a cys2362-to-phe (C2362F) substitution. Haplotype analysis indicated a founder effect. </p><p>Tjernberg et al. (2006) demonstrated that recombinant C2362F expressed in 293T human kidney cells resulted in significantly decreased expression of the mutant protein (8% of controls), although there was similar production. The findings indicated increased intracellular retention of the mutant protein. The mutant protein produced showed less of the multimeric structure, suggesting that the loss of a cysteine on an interchain bond impaired normal multimerization, since there was no difference in subunit size from the wildtype. There was also no evidence of a dominant-negative effect, suggesting that the ultimate effects of the C2362F mutation were similar to that of a null allele. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0035 VON WILLEBRAND DISEASE, TYPE 2N</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, TYR357TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61754002,
|
|
|
|
|
|
|
|
ClinVar: RCV000000344, RCV000086555
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 20-year-old French woman with VWD type 2N (see 613554), Mazurier et al. (2002) identified compound heterozygosity for 2 mutations in the VWF gene: a 1071C-A transversion in exon 9, resulting in a tyr357-to-ter (Y357X) substitution, and a 3178T-C transition in exon 24, resulting in a cys1060-to-arg (C1060R; 613160.0036) substitution. The authors noted that the Y357X mutation is a type 3 mutation (277480) presumably because it represents a truncating mutation and lack of protein expression. The patient had very low levels of VWF and F8, and absent binding of VWF to F8. She had epistaxis, hematomas, and hematemesis throughout childhood. The diagnosis was complicated at first because 2 male first cousins had F8 deficiency (306700) due to a hemizygous mutation in the F8 gene (C179G; 300841.0268). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0036 VON WILLEBRAND DISEASE, TYPE 2N</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, CYS1060ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61748497,
|
|
|
|
|
|
|
|
ClinVar: RCV000000345, RCV000086640
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 613160.0035 and Mazurier et al. (2002). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0037 VON WILLEBRAND DISEASE, TYPE 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, ASN528SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61754010,
|
|
|
|
|
|
gnomAD: rs61754010,
|
|
|
|
|
|
ClinVar: RCV000000346, RCV000086569, RCV002243608
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 Turkish boys, born of consanguineous parents, with VWD type 2A (see 613554), Haberichter et al. (2010) identified a homozygous 1583A-G transition in exon 14 of the VWF gene, resulting in an asn528-to-ser (N528S) substitution in the D2 domain of the propeptide. The phenotype was characterized by significant mucocutaneous bleeding beginning in childhood; 1 patient had joint bleeding. The patients had decreased plasma and platelet VWF antigen and decreased platelet VWF binding to collagen, with only slightly reduced F8 activity. There was a poor VWF response to desmopressin infusion, indicating lack of VWF storage in endothelial cells. The VWF multimer pattern lacked both high molecular weight multimers and medium-sized multimers particularly severe in platelets, consistent with VWD type 2A and the historical subclassification of type IIC. In vitro functional expression studies in mammalian cells showed that the N528S mutation introduced into a full-length VWF expression vector resulted in decreased VWF secretion (7.5% of controls) with an abnormal multimer pattern lacking both high molecular weight and medium-sized multimers, and lack of proper trafficking to storage granules. Detailed studies using coexpression of the mutant and wildtype propeptide with mutant and wildtype full-length VWF indicated a defective interaction of VWF with its intracellular propeptide chaperone, resulting in loss of regulated storage of VWF. Heterozygous expression of the mutant and wildtype alleles resulted in normal VWF secretion and multimerization, confirming the recessive nature of this mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0038 VON WILLEBRAND DISEASE, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
VON WILLEBRAND DISEASE, TYPE 1, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, 8.6-KB DEL, EX4-5
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000144413, RCV002271339, RCV002271340
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 Caucasian British patients, including 2 sibs, with VWD type 3 (277480), Sutherland et al. (2009) identified a homozygous 8,631-bp deletion in the VWF gene, resulting in an in-frame deletion of exons 4 and 5. The deletion spanned from within intron 3 to within intron 5, and the breakpoints occurred in inverted AluY repeat elements. Analysis of other patients with VWD type 3 showed that 4 were compound heterozygous for the exon 4-5 deletion and another pathogenic mutation, and 1 was heterozygous for the deletion but with no second mutation detected. In total, 7 of 12 white patients with VWD type 3 carried this deletion, which was not found in 9 patients of Asian origin. Haplotype analysis confirmed a founder effect in the white British population. Heterozygosity for this deletion was found in 2 of 34 probands with VWD type 1 (193400), their affected family members, and 1 unaffected family member, indicating reduced penetrance. An unrelated patient with VWD type 1 was also found to carry a heterozygous deletion. In vitro functional expression studies showed that the deletion resulted in significantly decreased protein secretion, with a 98% decrease in the homozygous state and an 86% decrease in the heterozygous state, consistent with a dominant-negative effect. Expression of the homozygous mutation, but not of the heterozygous mutation, resulted in defective multimer production. The mutation was not found in 200 control alleles. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0039 VON WILLEBRAND DISEASE, TYPE 2A/IIE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, TYR1146CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267607326,
|
|
|
|
|
|
|
|
ClinVar: RCV000024001, RCV000086656, RCV000851956, RCV001800314, RCV002264640, RCV004821262
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 12 (32%) of 38 probands with von Willebrand disease type 2A/IIE (see 613554), Schneppenheim et al. (2010) identified a heterozygous 3437A-C transversion in exon 26 of the VWF gene, resulting in a tyr1146-to-cys (Y1146C) substitution in the D3 domain. Plasma from patients showed complete absence of large VWF multimers, and in vitro expression studies indicated that the Y1146C-mutant protein caused a severe reduction in or lack of high molecular weight monomers. and decreased secreted VWF antigen levels. However, clinical symptoms were heterogeneous among carriers, ranging from mild to severe bleeding. Schneppenheim et al. (2010) suggested several mechanisms acting in concert, including decreased secretion of VWF, the change affecting a cysteine residue which may impact multimerization, and decreased half-life of the mutant protein. Altered ADAMTS13-mediated proteolysis did not appear to be a primary factor. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0040 VON WILLEBRAND DISEASE, TYPE 2CB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, TRP1745CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267607352,
|
|
|
|
|
|
|
|
ClinVar: RCV000086831, RCV002271338, RCV004821273
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an elderly woman with von Willebrand disease type 2CB (see 613554), Riddell et al. (2009) identified compound heterozygosity for 2 mutations in the VWF gene: a 5235G-T transversion in exon 30, resulting in a trp1745-to-cys (W1745C) substitution in the A3 domain, and R760H (613160.0041). She had a lifelong history of severe bleeding episodes, including epistaxis, ecchymosis, menorrhagia, and bleeding after dental extractions. The proband had 2 offspring, each of whom was heterozygous for 1 of the mutations and showed minor bleeding symptoms not requiring treatment. Both persons with the W1745C mutation had markedly reduced ratios of VWF collagen-binding activity to VWF antigen (CB:Ag) against type III collagen and type I collagen. There were normal values of VWF:RCo to VWF:Ag (RCo:Ag), normal VWF multimer analysis, and normal ristocetin-induced platelet aggregation. Treatment of the mother with DDAVP resulted in a good functional response with a rise in VWF:CB resulting from an overall increase in the amount of circulating VWF, even though the qualitative defect in collagen binding remained. These findings and in vitro expression studies indicated that the W1745C-mutant protein caused a specific defect in collagen binding, which Riddell et al. (2009) suggested represented a novel classification subtype termed 'VWF 2CB.' </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0041 VON WILLEBRAND DISEASE, TYPE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, ARG760HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs61748467,
|
|
|
|
|
|
gnomAD: rs61748467,
|
|
|
|
|
|
ClinVar: RCV000024003, RCV000086595
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with a mild bleeding tendency and laboratory studies consistent with VWD type 1 (193400), Riddell et al. (2009) identified a heterozygous 2279G-A transition in the VWF gene, resulting in an arg760-to-his (R760H; 613160.0041) substitution. Laboratory studies showed a concordant reduction in VWF:Ag, VWF:RCo, and VWF:CB, with a normal multimer pattern. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0042 VON WILLEBRAND DISEASE, TYPE 2CB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
VWF, SER1783ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267607353,
|
|
|
|
|
|
gnomAD: rs267607353,
|
|
|
|
|
|
ClinVar: RCV000024004, RCV000086836, RCV002468978
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a mother and son with VWD type 2CB (see 613554), Riddell et al. (2009) identified a heterozygous 5347T-G transversion in exon 31 of the VWF gene, resulting in a ser1783-to-ala (S1783A) substitution in the A3 domain. Laboratory studies showed normal VWF:Ag, VWF:RCo, and multimers, but decreased binding to both collagen I and collagen III. Defective collagen binding was confirmed by in vitro expression studies. Treatment with DDAVP resulted in a good functional response with a rise in VWF:CB resulting from an overall increase in the amount of circulating VWF, even though the qualitative defect in collagen binding remained. These findings indicated that the S1783A-mutant protein caused a specific defect in collagen binding, which Riddell et al. (2009) suggested represented a novel classification subtype termed 'VWF 2CB.' </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Bahou et al. (1988); Bonthron et al. (1986); Castaman et al. (1999);
|
|
Cumming et al. (1992); Fay et al. (1986); Ginsburg (1999); Hoyer
|
|
(1981); Mazurier et al. (1990); Meyer et al. (1978); Nachman et al.
|
|
(1980); Ngo et al. (1988); Ruggeri et al. (1982); Ruggeri and
|
|
Zimmerman (1980); Saba et al. (1985); Verweij et al. (1985)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Andrews, R. K., Booth, W. J., Gorman, J. J., Castaldi, P. A., Berndt, M. C.
|
|
<strong>Purification of botrocetin from Bothrops jararaca venom: analysis of the botrocetin-mediated interaction between von Willebrand factor and the human platelet membrane glycoprotein Ib-IX complex.</strong>
|
|
Biochemistry 28: 8317-8326, 1989.
|
|
|
|
|
|
[PubMed: 2557900]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1021/bi00447a009]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bahou, W. F., Bowie, E. J. W., Fass, D. N., Ginsburg, D.
|
|
<strong>Molecular genetic analysis of porcine von Willebrand disease: tight linkage to the von Willebrand factor locus.</strong>
|
|
Blood 72: 308-313, 1988.
|
|
|
|
|
|
[PubMed: 2898953]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Barrow, L. L., Simin, K., Mohlke, K., Nichols, W. C., Ginsburg, D., Meisler, M. H.
|
|
<strong>Conserved linkage of neurotrophin-3 and von Willebrand factor on mouse chromosome 6.</strong>
|
|
Mammalian Genome 4: 343-345, 1993.
|
|
|
|
|
|
[PubMed: 8318738]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00357095]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bernardi, F., Marchetti, G., Guerra, S., Casonato, A., Gemmati, D., Patracchini, P., Ballerini, G., Conconi, F.
|
|
<strong>A de novo and heterozygous gene deletion causing a variant of von Willebrand disease.</strong>
|
|
Blood 75: 677-683, 1990.
|
|
|
|
|
|
[PubMed: 1967540]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bodo, I., Katsumi, A., Tuley, E. A., Eikenboom, J. C. J., Dong, Z., Sadler, J. E.
|
|
<strong>Type 1 von Willebrand disease mutation cys1149-to-arg causes intracellular retention and degradation of heterodimers: a possible general mechanism for dominant mutations of oligomeric proteins.</strong>
|
|
Blood 98: 2973-2979, 2001.
|
|
|
|
|
|
[PubMed: 11698279]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood.v98.10.2973]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bonthron, D., Orr, E. C., Mitsock, L. M., Ginsburg, D., Handin, R. I., Orkin, S. H.
|
|
<strong>Nucleotide sequence of pre-pro-von Willebrand factor cDNA.</strong>
|
|
Nucleic Acids Res. 14: 7125-7127, 1986.
|
|
|
|
|
|
[PubMed: 3489923]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/14.17.7125]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bonthron, D. T., Handin, R. I., Kaufman, R. J., Wasley, L. C., Orr, E. C., Mitsock, L. M., Ewenstein, B., Loscalzo, J., Ginsburg, D., Orkin, S. H.
|
|
<strong>Structure of pre-pro-von Willebrand factor and its expression in heterologous cells.</strong>
|
|
Nature 324: 270-273, 1986.
|
|
|
|
|
|
[PubMed: 3491324]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/324270a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bowen, D. J., Collins, P. W., Lester, W., Cumming, A. M., Keeney, S., Grundy, P., Enayat, S. M., Bolton-Maggs, P. H. B., Keeling, D. M., Khair, K., Tait, R. C., Wilde, J. T., Pasi, K. J., Hill, F. G.
|
|
<strong>The prevalence of the cysteine 1584 variant of von Willebrand factor is increased in type 1 von Willebrand disease: co-segregation with increased susceptibility to ADAMTS13 proteolysis but not clinical phenotype.</strong>
|
|
Brit. J. Haemat. 128: 830-836, 2005.
|
|
|
|
|
|
[PubMed: 15755288]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.2005.05375.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bowen, D. J., Collins, P. W.
|
|
<strong>An amino acid polymorphism in von Willebrand factor correlates with increased susceptibility to proteolysis by ADAMTS13.</strong>
|
|
Blood 103: 941-947, 2004.
|
|
|
|
|
|
[PubMed: 14525793]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2003-05-1505]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cao, W., Krishnaswamy, S., Camire, R. M., Lenting, P. J., Zheng, X. L.
|
|
<strong>Factor VIII accelerates proteolytic cleavage of von Willebrand factor by ADAMTS13.</strong>
|
|
Proc. Nat. Acad. Sci. 105: 7416-7421, 2008.
|
|
|
|
|
|
[PubMed: 18492805]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0801735105]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Casonato, A., Pontara, E., Sartorello, F., Cattini, M. G., Sartori, M. T., Padrini, R., Girolami, A.
|
|
<strong>Reduced von Willebrand factor survival in type Vicenza von Willebrand disease.</strong>
|
|
Blood 99: 180-184, 2002.
|
|
|
|
|
|
[PubMed: 11756169]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood.v99.1.180]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Castaman, G., Eikenboom, J. C. J., Bertina, R. M., Rodeghiero, F.
|
|
<strong>Inconsistency of association between type 1 von Willebrand disease phenotype and genotype in families identified in an epidemiological investigation.</strong>
|
|
Thromb. Haemost. 82: 1065-1070, 1999.
|
|
|
|
|
|
[PubMed: 10494765]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Castaman, G., Rodeghiero, F., Mannucci, P. M.
|
|
<strong>The elusive pathogenesis of von Willebrand disease Vicenza. (Letter)</strong>
|
|
Blood 99: 4243-4244, 2002.
|
|
|
|
|
|
[PubMed: 12043692]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood.v99.11.4243]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Collins, C. J., Underdahl, J. P., Levene, R. B., Ravera, C. P., Morin, M. J., Dombalagian, M. J., Ricca, G., Livingston, D. M., Lynch, D. C.
|
|
<strong>Molecular cloning of the human gene for von Willebrand factor and identification of the transcription initiation site.</strong>
|
|
Proc. Nat. Acad. Sci. 84: 4393-4397, 1987.
|
|
|
|
|
|
[PubMed: 3496594]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.84.13.4393]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cooney, K. A., Nichols, W. C., Bruck, M. E., Bahou, W. F., Shapiro, A. D., Bowie, E. J. W., Gralnick, H. R., Ginsburg, D.
|
|
<strong>The molecular defect in type IIB von Willebrand disease: identification of four potential missense mutations within the putative GpIb binding domain.</strong>
|
|
J. Clin. Invest. 87: 1227-1233, 1991.
|
|
|
|
|
|
[PubMed: 1672694]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI115123]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cumming, A., Grundy, P., Keeney, S., Lester, W., Enayat, S., Guilliatt, A., Bowen, D., Pasi, J., Keeling, D., Hill, F., Bolton-Maggs, P. H., Hay, C., Collins, P. B.
|
|
<strong>An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease.</strong>
|
|
Thromb. Haemost. 96: 630-641, 2006.
|
|
|
|
|
|
[PubMed: 17080221]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cumming, A. M., Armstrong, J. G., Pendry, K., Burn, A. M., Wensley, R. T.
|
|
<strong>Polymerase chain reaction amplification of two polymorphic simple repeat sequences within the von Willebrand factor gene: application to family studies in von Willebrand disease.</strong>
|
|
Hum. Genet. 89: 194-198, 1992.
|
|
|
|
|
|
[PubMed: 1587530]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00217122]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Denis, C., Methia, N., Frenette, P. S., Rayburn, H., Ullman-Cullere, M., Hynes, R. O., Wagner, D. D.
|
|
<strong>A mouse model of severe von Willebrand disease: defects in hemostasis and thrombosis.</strong>
|
|
Proc. Nat. Acad. Sci. 95: 9524-9529, 1998.
|
|
|
|
|
|
[PubMed: 9689113]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.95.16.9524]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dent, J. A., Berkowitz, S. D., Ware, J., Kasper, C. K., Ruggeri, Z. M.
|
|
<strong>Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 6306-6310, 1990. Note: Erratum: Proc. Nat. Acad. Sci. 87: 9508 only, 1990.
|
|
|
|
|
|
[PubMed: 2385594]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.87.16.6306]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Donner, M., Andersson, A.-M., Kristoffersson, A.-C., Nilsson, I. M., Dahlback, B., Holmberg, L.
|
|
<strong>An arg545-to-cys substitution mutation of the von Willebrand factor in type IIB von Willebrand's disease.</strong>
|
|
Europ. J. Haemat. 47: 342-345, 1991.
|
|
|
|
|
|
[PubMed: 1761120]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1600-0609.1991.tb01858.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Donner, M., Kristoffersson, A. C., Lenk, H., Scheibel, E., Dahlback, B., Nilsson, I. M., Holmberg, L.
|
|
<strong>Type IIB von Willebrand's disease: gene mutations and clinical presentation in nine families from Denmark, Germany and Sweden.</strong>
|
|
Brit. J. Haemat. 82: 58-65, 1992.
|
|
|
|
|
|
[PubMed: 1419803]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1992.tb04594.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eikenboom, J. C. J., Castaman, G., Vos, H. L., Bertina, R. M., Rodeghiero, F.
|
|
<strong>Characterization of the genetic defects in recessive type 1 and type 3 von Willebrand disease patients of Italian origin.</strong>
|
|
Thromb. Haemost. 79: 709-717, 1998.
|
|
|
|
|
|
[PubMed: 9569178]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eikenboom, J. C. J., Matsushita, T., Reitsma, P. H., Tuley, E. A., Castaman, G., Briet, E., Sadler, J. E.
|
|
<strong>Dominant type 1 von Willebrand disease caused by mutated cysteine residues in the D3 domain of von Willebrand factor.</strong>
|
|
Blood 88: 2433-2441, 1996.
|
|
|
|
|
|
[PubMed: 8839833]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eikenboom, J. C. J., Vink, T., Briet, E., Sixma, J. J., Reitsma, P. H.
|
|
<strong>Multiple substitutions in the von Willebrand factor gene that mimic the pseudogene sequence.</strong>
|
|
Proc. Nat. Acad. Sci. 91: 2221-2224, 1994.
|
|
|
|
|
|
[PubMed: 8134377]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.91.6.2221]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fay, P. J., Kawai, Y., Wagner, D. D., Ginsburg, D., Bonthron, D., Ohlsson-Wilhelm, B. M., Chavin, S. I., Abraham, G. N., Handin, R. I., Orkin, S. H., Montgomery, R. R., Marder, V. J.
|
|
<strong>Propolypeptide of von Willebrand factor circulates in blood and is identical to von Willebrand antigen II.</strong>
|
|
Science 232: 995-998, 1986.
|
|
|
|
|
|
[PubMed: 3486471]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.3486471]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Flood, V. H., Gill, J. C., Morateck, P. A., Christopherson, P. A., Friedman, K. D., Haberichter, S. L., Branchford, B. R., Hoffmann, R. G., Abshire, T. C., Di Paola, J. A., Hoots, W. K, Leissinger, C., Lusher, J. M., Ragni, M. V., Shapiro, A. D., Montgomery, R. R.
|
|
<strong>:Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor.</strong>
|
|
Blood 116: 280-286, 2010.
|
|
|
|
|
|
[PubMed: 20231421]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2009-10-249102]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gao, W., Anderson, P. J., Sadler, J. E.
|
|
<strong>Extensive contacts between ADAMTS13 exosites and von Willebrand factor domain A2 contribute to substrate specificity.</strong>
|
|
Blood 112: 1713-1719, 2008.
|
|
|
|
|
|
[PubMed: 18492952]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2008-04-148759]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gaucher, C., Hanss, M., Dechavanne, M., Mazurier, C.
|
|
<strong>Substitution of cysteine for phenylalanine 751 in mature von Willebrand factor is a novel candidate mutation in a family with type IIA von Willebrand disease.</strong>
|
|
Brit. J. Haemat. 83: 94-99, 1993.
|
|
|
|
|
|
[PubMed: 8435341]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1993.tb04637.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gaucher, C., Jorieux, S., Mercier, B., Oufkir, D., Mazurier, C.
|
|
<strong>The 'Normandy' variant of von Willebrand disease: characterization of a point mutation in the von Willebrand factor gene.</strong>
|
|
Blood 77: 1937-1941, 1991.
|
|
|
|
|
|
[PubMed: 2018834]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gaucher, C., Mercier, B., Jorieux, S., Oufkir, D., Mazurier, C.
|
|
<strong>Identification of two point mutations in the von Willebrand factor gene of three families with the 'Normandy' variant of von Willebrand disease.</strong>
|
|
Brit. J. Haemat. 78: 506-514, 1991.
|
|
|
|
|
|
[PubMed: 1832934]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1991.tb04480.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ginsburg, D., Handin, R. I., Bonthron, D. T., Donlon, T. A., Bruns, G. A. P., Latt, S. A., Orkin, S. H.
|
|
<strong>Human von Willebrand factor (vWF): isolation of complementary DNA (cDNA) clones and chromosomal localization.</strong>
|
|
Science 228: 1401-1406, 1985.
|
|
|
|
|
|
[PubMed: 3874428]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.3874428]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ginsburg, D., Konkle, B. A., Gill, J. C., Montgomery, R. R., Bockenstedt, P. L., Johnson, T. A., Yang, A. Y.
|
|
<strong>Molecular basis of human von Willebrand disease: analysis of platelet von Willebrand factor mRNA.</strong>
|
|
Proc. Nat. Acad. Sci. 86: 3723-3727, 1989.
|
|
|
|
|
|
[PubMed: 2786201]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.86.10.3723]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ginsburg, D., Sadler, J. E.
|
|
<strong>Von Willebrand disease: a database of point mutations, insertions, and deletions.</strong>
|
|
Thromb. Haemost. 69: 177-184, 1993.
|
|
|
|
|
|
[PubMed: 8456431]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ginsburg, D.
|
|
<strong>Molecular genetics of von Willebrand disease.</strong>
|
|
Thromb. Haemost. 82: 585-591, 1999.
|
|
|
|
|
|
[PubMed: 10605755]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Golder, M., Pruss, C. M., Hegadorn, C., Mewburn, J., Laverty, K., Sponagle, K., Lillicrap, D.
|
|
<strong>Mutation-specific hemostatic variability in mice expressing common type 2B von Willebrand disease substitutions.</strong>
|
|
Blood 115: 4862-4869, 2010.
|
|
|
|
|
|
[PubMed: 20371742]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2009-11-253120]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goodeve, A. C.
|
|
<strong>The genetic basis of von Willebrand disease.</strong>
|
|
Blood Rev. 24: 123-134, 2010.
|
|
|
|
|
|
[PubMed: 20409624]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.blre.2010.03.003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Haberichter, S. L., Budde, U., Obser, T., Schneppenheim, S., Wermes, C., Schneppenheim, R.
|
|
<strong>The mutation N528S in the von Willebrand factor (VWF) propeptide causes defective multimerization and storage of VWF.</strong>
|
|
Blood 115: 4580-4587, 2010.
|
|
|
|
|
|
[PubMed: 20335223]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2009-09-244327]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hagiwara, T., Inaba, H., Yoshida, S., Nagaizumi, K., Arai, M., Hanabusa, H., Fukutake, K.
|
|
<strong>A novel mutation gly1672-to-arg in type 2A and a homozygous mutation in type 2B von Willebrand disease.</strong>
|
|
Thromb. Haemost. 76: 253-257, 1996.
|
|
|
|
|
|
[PubMed: 8865541]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hilbert, L., Jorieux, S., Fontenay-Roupie, M., Guicheteau, M., Fressinaud, E., Meyer, D., Mazurier, C., the INSERM Network on Molecular Abnormalities in von Willebrand Disease.
|
|
<strong>Expression of two type 2N von Willebrand disease mutations identified in exon 18 of von Willebrand factor gene.</strong>
|
|
Brit. J. Haemat. 127: 184-189, 2004.
|
|
|
|
|
|
[PubMed: 15461624]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.2004.05187.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Holmberg, L., Berntorp, E., Donner, M., Nilsson, I. M.
|
|
<strong>von Willebrand's disease characterised by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers.</strong>
|
|
Blood 68: 668-672, 1986.
|
|
|
|
|
|
[PubMed: 3488775]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Holmberg, L., Dent, J. A., Schneppenheim, R., Budde, U., Ware, J., Ruggeri, Z. M.
|
|
<strong>von Willebrand factor mutation enhancing interaction with platelets in patients with normal multimeric structure.</strong>
|
|
J. Clin. Invest. 91: 2169-2177, 1993.
|
|
|
|
|
|
[PubMed: 8486782]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI116443]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Holmberg, L., Karpman, D., Isaksson, C., Kristoffersson, A. C., Lethagen, S., Schneppenheim, R.
|
|
<strong>Ins405-asn-pro mutation in the von Willebrand factor propeptide in recessive type 2A (IIC) von Willebrand's disease.</strong>
|
|
Thromb. Haemost. 79: 718-722, 1998.
|
|
|
|
|
|
[PubMed: 9569179]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Howard, M. A., Perkin, J., Salem, H. H., Firkin, B. G.
|
|
<strong>The agglutination of human platelets by botrocetin: evidence that botrocetin and ristocetin act at different sites on the factor VIII molecule and platelet membrane.</strong>
|
|
Brit. J. Haemat. 57: 25-35, 1984.
|
|
|
|
|
|
[PubMed: 6426499]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1984.tb02862.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hoyer, L. W.
|
|
<strong>The factor VIII complex: structure and function.</strong>
|
|
Blood 58: 1-13, 1981.
|
|
|
|
|
|
[PubMed: 6165414]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Huizinga, E. G., Tsuji, S., Romijn, R. A. P., Schiphorst, M. E., de Groot, P. G., Sixma, J. J., Gros, P.
|
|
<strong>Structures of glycoprotein Ib-alpha and its complex with von Willebrand factor A1 domain.</strong>
|
|
Science 297: 1176-1179, 2002.
|
|
|
|
|
|
[PubMed: 12183630]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.107355]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Iannuzzi, M. C., Hidaka, N., Boehnke, M., Bruck, M. E., Hanna, W. T., Collins, F. S., Ginsburg, D.
|
|
<strong>Analysis of the relationship of von Willebrand disease (vWD) and hereditary hemorrhagic telangiectasia and identification of a potential type IIA vWD mutation (ile865-to-thr).</strong>
|
|
Am. J. Hum. Genet. 48: 757-763, 1991.
|
|
|
|
|
|
[PubMed: 1673047]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jackson, S. C., Sinclair, G. D., Cloutier, S., Duan, Z., Rand, M. L., Poon, M.-C.
|
|
<strong>The Montreal platelet syndrome kindred has type 2B von Willebrand disease with the VWF V1316M mutation.</strong>
|
|
Blood 113: 3348-3351, 2009.
|
|
|
|
|
|
[PubMed: 19060241]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2008-06-165233]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kokame, K., Matsumoto, M., Fujimura, Y., Miyata, T.
|
|
<strong>VWF73, a region from D1596 to R1668 of von Willebrand factor, provides a minimal substrate for ADAMTS-13.</strong>
|
|
Blood 103: 607-612, 2004.
|
|
|
|
|
|
[PubMed: 14512308]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2003-08-2861]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kyrle, P. A., Niessner, H., Dent, J., Panzer, S., Brenner, B., Zimmerman, T. S., Lechner, K.
|
|
<strong>IIB von Willebrand's disease: pathogenetic and therapeutic studies.</strong>
|
|
Brit. J. Haemat. 69: 55-59, 1988.
|
|
|
|
|
|
[PubMed: 3132965]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1988.tb07602.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lavergne, J.-M., De Paillette, L., Bahnak, B. R., Ribba, A.-S., Fressinaud, E., Meyer, D., Pietu, G.
|
|
<strong>Defects in type IIA von Willebrand disease: a cysteine 509 to arginine substitution in the mature von Willebrand factor disrupts a disulphide loop involved in the interaction with platelet glycoprotein Ib-IX.</strong>
|
|
Brit. J. Haemat. 82: 66-72, 1992.
|
|
|
|
|
|
[PubMed: 1419804]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1992.tb04595.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lester, W. A., Guilliatt, A. M., Surdhar, G. K., Enayat, S. M., Wilde, J. T., Willoughby, S., Grundy, P., Cumming, A. M., Collins, P. W., Hill, F. G. H.
|
|
<strong>Inherited and de novo von Willebrand disease 'Vicenza' in UK families with the R1205H mutation: diagnostic pitfalls and new insights.</strong>
|
|
Brit. J. Haemat. 135: 91-96, 2006.
|
|
|
|
|
|
[PubMed: 16925796]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.2006.06251.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lynch, D. C., Zimmerman, T. S., Collins, C. J., Morin, M. J., Ling, E. H., Livingston, D. M.
|
|
<strong>Molecular cloning of mRNA for human von Willebrand factor. (Abstract)</strong>
|
|
Clin. Res. 33: 548, 1985.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lynch, D. C., Zimmerman, T. S., Ruggeri, Z. M.
|
|
<strong>Von Willebrand factor, now cloned. (Annotation).</strong>
|
|
Brit. J. Haemat. 64: 15-20, 1986.
|
|
|
|
|
|
[PubMed: 3489483]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1986.tb07569.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mancuso, D. J., Tuley, E. A., Westfield, L. A., Lester-Mancuso, T. L., Le Beau, M. M., Sorace, J. M., Sadler, J. E.
|
|
<strong>Human von Willebrand factor gene and pseudogene: structural analysis and differentiation by polymerase chain reaction.</strong>
|
|
Biochemistry 30: 253-269, 1991.
|
|
|
|
|
|
[PubMed: 1988024]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1021/bi00215a036]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mancuso, D. J., Tuley, E. A., Westfield, L. A., Worrall, N. K., Shelton-Inloes, B. B., Sorace, J. M., Alevy, Y. G., Sadler, J. E.
|
|
<strong>Structure of the gene for human von Willebrand factor.</strong>
|
|
J. Biol. Chem. 264: 19514-19527, 1989.
|
|
|
|
|
|
[PubMed: 2584182]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mannucci, P. M., Lombardi, R., Castaman, G., Dent, J. A., Lattuada, A., Rodeghiero, F., Zimmerman, T. S.
|
|
<strong>Von Willebrand disease 'Vicenza' with larger-than-normal (supranormal) von Willebrand factor multimers.</strong>
|
|
Blood 71: 65-70, 1988.
|
|
|
|
|
|
[PubMed: 3257148]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mazurier, C., Dieval, J., Jorieux, S., Delobel, J., Goudemand, M.
|
|
<strong>A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF: characterization of abnormal vWF/FVIII interaction.</strong>
|
|
Blood 75: 20-26, 1990.
|
|
|
|
|
|
[PubMed: 2104761]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mazurier, C., Gaucher, C., Jorieux, S., Parquet-Gernez, A., Goudemand, M.
|
|
<strong>Evidence for a von Willebrand factor defect in factor VIII binding in three members of a family previously misdiagnosed mild haemophilia A and haemophilia A carriers: consequences for therapy and genetic counselling.</strong>
|
|
Brit. J. Haemat. 76: 372-379, 1990.
|
|
|
|
|
|
[PubMed: 2124499]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1990.tb06371.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mazurier, C., Parquet-Gernez, A., Gaucher, C., Lavergne, J.-M., Goudemand, J.
|
|
<strong>Factor VIII deficiency not induced by FVIII gene mutation in a female first cousin of two brothers with haemophilia A.</strong>
|
|
Brit. J. Haemat. 119: 390-392, 2002.
|
|
|
|
|
|
[PubMed: 12406074]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.2002.03819.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mertes, G., Ludwig, M., Schwaab, R., Brackmann, H.-H., Olek, K.
|
|
<strong>Delta C in exon 18 of the von Willebrand gene is uncommon in German vWD type III patients. (Letter)</strong>
|
|
Thromb. Haemost. 70: 1064-1065, 1993.
|
|
|
|
|
|
[PubMed: 8165603]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meyer, D., McKee, P. A., Hoyer, L. W., Zimmerman, T. S., Gralnick, H. R.
|
|
<strong>Molecular biology of factor VIII--von Willebrand factor.</strong>
|
|
Thromb. Haemost. 40: 245-251, 1978.
|
|
|
|
|
|
[PubMed: 310584]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Michaux, G., Abbitt, K. B., Collinson, L. M., Haberichter, S. L., Norman, K. E., Cutler, D. F.
|
|
<strong>The physiological function of von Willebrand's factor depends on its tubular storage in endothelial Weibel-Palade bodies.</strong>
|
|
Dev. Cell 10: 223-232, 2006.
|
|
|
|
|
|
[PubMed: 16459301]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.devcel.2005.12.012]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Milton, J. G., Frojmovic, M. M., Tang, S. S., White, J. G.
|
|
<strong>Spontaneous platelet aggregation in a hereditary giant platelet syndrome (MPS).</strong>
|
|
Am. J. Path. 114: 336-345, 1984.
|
|
|
|
|
|
[PubMed: 6696046]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Murray, E. W., Giles, A. R., Lillicrap, D.
|
|
<strong>Germ-line mosaicism for a valine-to-methionine substitution at residue 553 in the glycoprotein Ib-binding domain of von Willebrand factor, causing type IIB von Willebrand disease.</strong>
|
|
Am. J. Hum. Genet. 50: 199-207, 1992.
|
|
|
|
|
|
[PubMed: 1729889]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nachman, R. L., Jaffe, E. A., Miller, C., Brown, W. T.
|
|
<strong>Structural analysis of factor VIII antigen in von Willebrand disease.</strong>
|
|
Proc. Nat. Acad. Sci. 77: 6832-6836, 1980.
|
|
|
|
|
|
[PubMed: 6161373]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.77.11.6832]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ngo, K. Y., Glotz, V. T., Koziol, J. A., Lynch, D. C., Gitschier, J., Ranieri, P., Ciavarella, N., Ruggeri, Z. M., Zimmerman, T. S.
|
|
<strong>Homozygous and heterozygous deletions of the von Willebrand factor gene in patients and carriers of severe von Willebrand disease.</strong>
|
|
Proc. Nat. Acad. Sci. 85: 2753-2757, 1988.
|
|
|
|
|
|
[PubMed: 3258663]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.85.8.2753]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
NIH/CEPH Collaborative Mapping Group.
|
|
<strong>A comprehensive genetic linkage map of the human genome.</strong>
|
|
Science 258: 67-86, 1992.
|
|
|
|
|
|
[PubMed: 1439770]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
O'Brien, L. A., James, P. D., Othman, M., Berber, E., Cameron, C., Notley, C. R. P., Hegadorn, C. A., Sutherland, J. J., Hough, C., Rivard, G. E., O'Shaunessey, D., Association of Hemophilia Clinic Directors of Canada, Lillicrap, D.
|
|
<strong>Founder von Willebrand factor haplotype associated with type I von Willebrand disease.</strong>
|
|
Blood 102: 549-557, 2003.
|
|
|
|
|
|
[PubMed: 12649144]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2002-12-3693]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Patracchini, P., Marchetti, G., Aiello, V., Croci, G., Calzolari, E., Bernardi, F.
|
|
<strong>Characterization and mapping of the 5-prime portion of von Willebrand factor pseudogene.</strong>
|
|
Hum. Genet. 90: 297-298, 1992.
|
|
|
|
|
|
[PubMed: 1487245]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00220083]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Peake, I. R., Liddell, M. B., Moodie, P., Standen, G., Mancuso, D. J., Tuley, E. A., Westfield, L. A., Sorace, J. M., Sadler, J. E., Verweij, C. L., Bloom, A. L.
|
|
<strong>Severe type III von Willebrand's disease caused by deletion of exon 42 of the von Willebrand factor gene: family studies that identify carriers of the condition and a compound heterozygous individual.</strong>
|
|
Blood 75: 654-661, 1990.
|
|
|
|
|
|
[PubMed: 2297569]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Peerlinck, K., Eikenboom, J. C. J., Ploos Van Amstel, H. K., Sangtawesin, W., Arnout, J., Reitsma, P. H., Vermylen, J., Briet, E.
|
|
<strong>A patient with von Willebrand's disease characterized by a compound heterozygosity for a substitution of arg-854 by gln in the putative factor-VIII-binding domain of von Willebrand factor (vWF) on one allele and very low levels of mRNA from the second vWF allele.</strong>
|
|
Brit. J. Haemat. 80: 358-363, 1992.
|
|
|
|
|
|
[PubMed: 1581215]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1992.tb08145.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rabinowitz, I., Tuley, E. A., Mancuso, D. J., Randi, A. M., Firkin, B. G., Howard, M. A., Sadler, J. E.
|
|
<strong>Von Willebrand disease type B: a missense mutation selectively abolishes ristocetin-induced von Willebrand factor binding to platelet glycoprotein Ib.</strong>
|
|
Proc. Nat. Acad. Sci. 89: 9846-9849, 1992.
|
|
|
|
|
|
[PubMed: 1409710]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.89.20.9846]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Randi, A. M., Rabinowitz, I., Mancuso, D. J., Mannucci, P. M., Sadler, J. E.
|
|
<strong>Molecular basis of von Willebrand disease type IIB: candidate mutations cluster in one disulfide loop between proposed platelet glycoprotein Ib binding sequences.</strong>
|
|
J. Clin. Invest. 87: 1220-1226, 1991.
|
|
|
|
|
|
[PubMed: 2010538]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI115122]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Randi, A. M., Sacchi, E., Castaman, G. C., Rodeghiero, F., Mannucci, P. M.
|
|
<strong>The genetic defect of type I von Willebrand disease 'Vicenza' is linked to the von Willebrand factor gene.</strong>
|
|
Thromb. Haemost. 69: 173-176, 1993.
|
|
|
|
|
|
[PubMed: 8456430]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rayes, J., Hollestelle, M. J., Legendre, P., Marx, I., de Groot, P. G., Christophe, O. D., Lenting, P. J., Denis, C. V.
|
|
<strong>Mutation and ADAMTS13-dependent modulation of disease severity in a mouse model for von Willebrand disease type 2B.</strong>
|
|
Blood 115: 4870-4877, 2010.
|
|
|
|
|
|
[PubMed: 20200350]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2009-11-254193]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Riddell, A. F., Gomez, K., Millar, C. M., Mellars, G., Gill, S., Brown, S. A., Sutherland, M., Laffan, M. A., McKinnon, T. A.
|
|
<strong>Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor.</strong>
|
|
Blood 114: 3489-3496, 2009.
|
|
|
|
|
|
[PubMed: 19687512]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2008-10-184317]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M., Lombardi, R., Gatti, L., Bader, R., Valsecchi, C., Zimmerman, T. S.
|
|
<strong>Type IIB von Willebrand's disease: differential clearance of endogenous versus transfused large multimer von Willebrand factor.</strong>
|
|
Blood 60: 1453-1456, 1982.
|
|
|
|
|
|
[PubMed: 6982737]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M., Nilsson, I. M., Lombardi, R., Holmberg, L., Zimmerman, T. S.
|
|
<strong>Aberrant multimeric structure of von Willebrand factor in a new variant of von Willebrand's disease (type IIC).</strong>
|
|
J. Clin. Invest. 70: 1124-1127, 1982.
|
|
|
|
|
|
[PubMed: 6982283]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/jci110700]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M., Pareti, F. I., Mannucci, P. M., Ciavarella, N., Zimmerman, T. S.
|
|
<strong>Heightened interaction between platelets and factor VIII von Willebrand factor in a new subtype of von Willebrand's disease.</strong>
|
|
New Eng. J. Med. 302: 1047-1051, 1980.
|
|
|
|
|
|
[PubMed: 6767976]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198005083021902]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M., Zimmerman, T. S.
|
|
<strong>Variant von Willebrand's disease: characterization of two subtypes by analysis of multimeric composition of factor VIII-von Willebrand factor in plasma and platelets.</strong>
|
|
J. Clin. Invest. 65: 1318-1325, 1980.
|
|
|
|
|
|
[PubMed: 6773982]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI109795]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ruggeri, Z. M.
|
|
<strong>Von Willebrand factor.</strong>
|
|
J. Clin. Invest. 99: 559-564, 1997. Note: Erratum: J. Clin. Invest. 100: 237 only, 1997.
|
|
|
|
|
|
[PubMed: 9045854]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI119195]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Saba, H. I., Saba, S. R., Dent, J., Ruggeri, Z. M., Zimmerman, T. S.
|
|
<strong>Type IIB Tampa: a variant of von Willebrand disease with chronic thrombocytopenia, circulating platelet aggregates, and spontaneous platelet aggregation.</strong>
|
|
Blood 66: 282-286, 1985.
|
|
|
|
|
|
[PubMed: 3926021]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sadler, J. E., Budde, U., Eikenboom, J. C. J., Favaloro, E. J., Hill, F. G. H., Holmberg, L., Ingerslev, J., Lee, C. A., Lillicrap, D., Mannucci, P. M., Mazurier, C., Meyer, D., and 9 others.
|
|
<strong>Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor.</strong>
|
|
J. Thromb. Haemost. 4: 2103-2114, 2006.
|
|
|
|
|
|
[PubMed: 16889557]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1538-7836.2006.02146.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sadler, J. E., Ginsburg, D.
|
|
<strong>A database of polymorphisms in the von Willebrand factor gene and pseudogene.</strong>
|
|
Thromb. Haemost. 69: 185-191, 1993.
|
|
|
|
|
|
[PubMed: 8456432]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sadler, J. E., Shelton-Inloes, B. B., Sorace, J. M., Harlan, J. M., Titani, K., Davie, E. W.
|
|
<strong>Cloning and characterization of two cDNAs coding for human von Willebrand factor.</strong>
|
|
Proc. Nat. Acad. Sci. 82: 6394-6398, 1985.
|
|
|
|
|
|
[PubMed: 2864688]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.82.19.6394]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schneppenheim, R., Brassard, J., Krey, S., Budde, U., Kunicki, T. J., Holmberg, L., Ware, J., Ruggeri, Z. M.
|
|
<strong>Defective dimerization of von Willebrand factor subunits due to a cys-to-arg mutation in type IID von Willebrand disease.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 3581-3586, 1996.
|
|
|
|
|
|
[PubMed: 8622978]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.93.8.3581]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schneppenheim, R., Federici, A. B., Budde, U., Castaman, G., Drewke, E., Krey, S., Mannucci, P. M., Riesen, G., Rodeghiero, F., Zieger, B., Zimmermann, R.
|
|
<strong>Von Willebrand disease type 2M 'Vicenza' in Italian and German patients: identification of the first candidate mutation (G3864A; R1205H) in 8 families.</strong>
|
|
Thromb. Haemost. 83: 136-140, 2000.
|
|
|
|
|
|
[PubMed: 10669167]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schneppenheim, R., Michiels, J. J., Obser, T., Oyen, F., Pieconka, A., Schneppenheim, S., Will, K., Zieger, B., Budde, U.
|
|
<strong>A cluster of mutations in the D3 domain of von Willebrand factor correlates with a distinct subgroup of von Willebrand disease: type 2A/IIE.</strong>
|
|
Blood 115: 4894-4901, 2010.
|
|
|
|
|
|
[PubMed: 20351307]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2009-07-226324]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schneppenheim, R., Thomas, K. B., Krey, S., Budde, U., Jessat, U., Sutor, A. H., Zieger, B.
|
|
<strong>Identification of a candidate missense mutation in a family with von Willebrand disease type IIC.</strong>
|
|
Hum. Genet. 95: 681-686, 1995.
|
|
|
|
|
|
[PubMed: 7789955]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00209487]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shelton-Inloes, B. B., Chehab, F. F., Mannucci, P. M., Federici, A. B., Sadler, J. E.
|
|
<strong>Gene deletions correlate with the development of alloantibodies in von Willebrand disease.</strong>
|
|
J. Clin. Invest. 79: 1459-1465, 1987.
|
|
|
|
|
|
[PubMed: 3033024]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI112974]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sporn, L. A., Marder, V. J., Wagner, D. D.
|
|
<strong>Von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively.</strong>
|
|
Blood 69: 1531-1534, 1987.
|
|
|
|
|
|
[PubMed: 3105624]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stepanian, A., Ribba, A.-S., Lavergne, J.-M., Fressinaud, E., Juhan-Vague, I., Mazurier, C., Girma, J.-P., Meyer, D.
|
|
<strong>A new mutation, S1285F, within the A1 loop of von Willebrand factor induces a conformational change in A1 loop with abnormal binding to platelet GPIb and botrocetin causing type 2M von Willebrand disease.</strong>
|
|
Brit. J. Haemat. 120: 643-651, 2003.
|
|
|
|
|
|
[PubMed: 12588351]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.2003.04168.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sutherland, M. S., Cumming, A. M., Bowman, M., Bolton-Maggs, P. H. B., Bowen, D. J., Collins, P. W., Hay, C. R. M., Will, A. M., Keeney, S.
|
|
<strong>A novel deletion mutation is recurrent in von Willebrand disease types 1 and 3.</strong>
|
|
Blood 114: 1091-1098, 2009.
|
|
|
|
|
|
[PubMed: 19372260]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2008-08-173278]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Titani, K., Kumar, S., Takio, K., Ericsson, L. H., Wade, R. D., Ashida, K., Walsh, K. A., Chopek, M. W., Sadler, J. E., Fujikawa, K.
|
|
<strong>Amino acid sequence of human von Willebrand factor.</strong>
|
|
Biochemistry 25: 3171-3184, 1986.
|
|
|
|
|
|
[PubMed: 3524673]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1021/bi00359a015]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tjernberg, P., Castaman, G., Vos, H. L., Bertina, R. M., Eikenboom, J. C.
|
|
<strong>Homozygous C2362F von Willebrand factor induces intracellular retention of mutant von Willebrand factor resulting in autosomal recessive severe von Willebrand disease.</strong>
|
|
Brit. J. Haemat. 133: 409-418, 2006.
|
|
|
|
|
|
[PubMed: 16643449]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.2006.06055.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tuley, E. A., Gaucher, C., Jorieux, S., Worrall, N. K., Sadler, J. E., Mazurier, C.
|
|
<strong>Expression of von Willebrand factor 'Normandy': an autosomal mutation that mimics hemophilia A.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 6377-6381, 1991.
|
|
|
|
|
|
[PubMed: 1906179]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.88.14.6377]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Verweij, C. L., de Vries, C. J. M., Distel, B., van Zonneveld, A.-J., Geurts van Kessel, A., van Mourik, J. A., Pannekoek, H.
|
|
<strong>Construction of cDNA coding for human von Willebrand factor using antibody probes for colony-screening and mapping of the chromosomal gene.</strong>
|
|
Nucleic Acids Res. 13: 4699-4717, 1985.
|
|
|
|
|
|
[PubMed: 3875078]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/13.13.4699]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Verweij, C. L., Hofker, M., Quadt, R., Briet, E., Pannekoek, H.
|
|
<strong>RFLP for a human von Willebrand factor (vWF) cDNA clone, pvWF1100.</strong>
|
|
Nucleic Acids Res. 13: 8289 only, 1985. Note: Erratum: Nucleic Acids Res. 14: 1930 only, 1986.
|
|
|
|
|
|
[PubMed: 3877913]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/13.22.8289]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
von Willebrand, E. A.
|
|
<strong>Hereditar pseudohemofili.</strong>
|
|
Finska Lakar. Hand. 68: 87-112, 1926.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wagner, D. D., Saffaripour, S., Bonfanti, R., Sadler, J. E., Cramer, E. M., Chapman, B., Mayadas, T. N.
|
|
<strong>Induction of specific storage organelles by von Willebrand factor propolypeptide.</strong>
|
|
Cell 64: 403-413, 1991.
|
|
|
|
|
|
[PubMed: 1988154]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(91)90648-i]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ware, J., Dent, J. A., Azuma, H., Sugimoto, M., Kyrle, P. A., Yoshioka, A., Ruggeri, Z. M.
|
|
<strong>Identification of a point mutation in type IIB von Willebrand disease illustrating the regulation of von Willebrand factor affinity for the platelet membrane glycoprotein Ib-IX receptor.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 2946-2950, 1991.
|
|
|
|
|
|
[PubMed: 2011604]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.88.7.2946]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Weiss, J. G., Sussman, I. I.
|
|
<strong>Increased ristocetin-induced platelet aggregation (RIPA) and plasma von Willebrand factor (VWF) containing all VWF multimers (type I--New York). (Abstract)</strong>
|
|
Blood 66 (suppl. 1): 329, 1985.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wise, R. J., Ewenstein, B. M., Gorlin, J., Narins, S. C., Jesson, M., Handin, R. I.
|
|
<strong>Autosomal recessive transmission of hemophilia A due to a von Willebrand factor mutation.</strong>
|
|
Hum. Genet. 91: 367-372, 1993.
|
|
|
|
|
|
[PubMed: 8500791]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00217358]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wu, J.-J., Fujikawa, K., McMullen, B. A., Chung, D. W.
|
|
<strong>Characterization of a core binding site for ADAMTS-13 in the A2 domain of von Willebrand factor.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 18470-18474, 2006.
|
|
|
|
|
|
[PubMed: 17121983]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0609190103]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wylie, B., Gibson, J., Uhr, E., Kronenberg, H.
|
|
<strong>Von Willebrand's disease characterized by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers in plasma: a new subtype.</strong>
|
|
Pathology 20: 62-63, 1988.
|
|
|
|
|
|
[PubMed: 3259690]
|
|
|
|
|
|
[Full Text: https://doi.org/10.3109/00313028809085199]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, Z. P., Blomback, M., Nyman, D., Anvret, M.
|
|
<strong>Mutations of von Willebrand factor gene in families with von Willebrand disease in the Aland Islands.</strong>
|
|
Proc. Nat. Acad. Sci. 90: 7937-7940, 1993.
|
|
|
|
|
|
[PubMed: 8367445]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.90.17.7937]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, Z. P., Falk, G., Blomback, M., Egberg, N., Anvret, M.
|
|
<strong>A single cytosine deletion in exon 18 of the von Willebrand factor gene is the most common mutation in Swedish vWD type III patients.</strong>
|
|
Hum. Molec. Genet. 1: 767-768, 1992.
|
|
|
|
|
|
[PubMed: 1302613]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/1.9.767]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, Z. P., Falk, G., Blomback, M., Egberg, N., Anvret, M.
|
|
<strong>Identification of a new nonsense mutation in the von Willebrand factor gene in patients with von Willebrand disease type III.</strong>
|
|
Hum. Molec. Genet. 1: 61-62, 1992.
|
|
|
|
|
|
[PubMed: 1301136]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/1.1.61]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, Z. P., Lindstedt, M., Falk, G., Blomback, M., Egberg, N., Anvret, M.
|
|
<strong>Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I.</strong>
|
|
Am. J. Hum. Genet. 51: 850-858, 1992.
|
|
|
|
|
|
[PubMed: 1415226]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhou, M., Dong, X., Baldauf, C., Chen, H., Zhou, Y., Springer, T. A., Luo, X., Zhong, C., Grater, F., Ding, J.
|
|
<strong>A novel calcium-binding site of von Willebrand factor A2 domain regulates its cleavage by ADAMTS13.</strong>
|
|
Blood 117: 4623-4631, 2011.
|
|
|
|
|
|
[PubMed: 21385852]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2010-11-321596]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zieger, B., Budde, U., Jessat, U., Zimmermann, R., Simon, M., Katzel, R., Sutor, A. H.
|
|
<strong>New families with von Willebrand disease type 2M (Vicenza).</strong>
|
|
Thromb. Res. 87: 57-64, 1997.
|
|
|
|
|
|
[PubMed: 9253800]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0049-3848(97)00104-7]
|
|
|
|
|
|
</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">
|
|
Bao Lige - updated : 09/19/2019<br>Cassandra L. Kniffin - updated : 4/29/2013<br>Cassandra L. Kniffin - updated : 5/10/2011<br>Cassandra L. Kniffin - updated : 12/27/2010<br>Cassandra L. Kniffin - updated : 10/8/2010
|
|
</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">
|
|
Cassandra L. Kniffin : 12/1/2009
|
|
</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 : 01/07/2025<br>carol : 07/28/2023<br>carol : 07/27/2023<br>mgross : 09/19/2019<br>mgross : 09/19/2019<br>alopez : 11/07/2018<br>carol : 08/04/2016<br>carol : 07/07/2016<br>joanna : 6/29/2016<br>alopez : 5/21/2015<br>mgross : 11/18/2014<br>carol : 3/18/2014<br>alopez : 5/3/2013<br>ckniffin : 4/29/2013<br>carol : 4/18/2013<br>carol : 4/18/2013<br>terry : 4/4/2013<br>terry : 8/9/2012<br>carol : 7/6/2011<br>wwang : 6/13/2011<br>ckniffin : 5/10/2011<br>carol : 4/7/2011<br>terry : 1/7/2011<br>wwang : 1/5/2011<br>ckniffin : 12/27/2010<br>wwang : 11/2/2010<br>ckniffin : 10/8/2010<br>ckniffin : 10/8/2010<br>carol : 10/5/2010<br>carol : 10/4/2010<br>ckniffin : 9/29/2010<br>ckniffin : 12/4/2009
|
|
</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>
|
|
|
|
|