7737 lines
741 KiB
Text
7737 lines
741 KiB
Text
|
|
|
|
|
|
|
|
|
|
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
|
|
|
|
<head>
|
|
|
|
|
|
|
|
<!--
|
|
################################# CRAWLER WARNING #################################
|
|
|
|
- The terms of service and the robots.txt file disallows crawling of this site,
|
|
please see https://omim.org/help/agreement for more information.
|
|
|
|
- A number of data files are available for download at https://omim.org/downloads.
|
|
|
|
- We have an API which you can learn about at https://omim.org/help/api and register
|
|
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
|
|
|
|
- You should feel free to contact us at https://omim.org/contact to figure out the best
|
|
approach to getting the data you need for your work.
|
|
|
|
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
|
|
|
|
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
|
|
DISTRIBUTED CRAWLS OF THIS SITE.
|
|
|
|
################################# CRAWLER WARNING #################################
|
|
-->
|
|
|
|
|
|
|
|
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
|
|
<meta http-equiv="cache-control" content="no-cache" />
|
|
<meta http-equiv="pragma" content="no-cache" />
|
|
<meta name="robots" content="index, follow" />
|
|
|
|
|
|
<meta name="viewport" content="width=device-width, initial-scale=1" />
|
|
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
|
|
|
|
|
|
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
|
|
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
|
|
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
|
|
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
|
|
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
|
|
contain copious links to other genetics resources." />
|
|
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
|
|
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
|
|
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
|
|
<meta name="theme-color" content="#333333" />
|
|
<link rel="icon" href="/static/omim/favicon.png" />
|
|
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
|
|
<link rel="manifest" href="/static/omim/manifest.json" />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script id='mimBrowserCapability'>
|
|
function _0x5069(){const _0x4b1387=['91sZIeLc','mimBrowserCapability','15627zshTnf','710004yxXedd','34LxqNYj','match','disconnect','1755955rnzTod','observe','1206216ZRfBWB','575728fqgsYy','webdriver','documentElement','close','open','3086704utbakv','7984143PpiTpt'];_0x5069=function(){return _0x4b1387;};return _0x5069();}function _0xe429(_0x472ead,_0x43eb70){const _0x506916=_0x5069();return _0xe429=function(_0xe42949,_0x1aaefc){_0xe42949=_0xe42949-0x1a9;let _0xe6add8=_0x506916[_0xe42949];return _0xe6add8;},_0xe429(_0x472ead,_0x43eb70);}(function(_0x337daa,_0x401915){const _0x293f03=_0xe429,_0x5811dd=_0x337daa();while(!![]){try{const _0x3dc3a3=parseInt(_0x293f03(0x1b4))/0x1*(-parseInt(_0x293f03(0x1b6))/0x2)+parseInt(_0x293f03(0x1b5))/0x3+parseInt(_0x293f03(0x1b0))/0x4+-parseInt(_0x293f03(0x1b9))/0x5+parseInt(_0x293f03(0x1aa))/0x6+-parseInt(_0x293f03(0x1b2))/0x7*(parseInt(_0x293f03(0x1ab))/0x8)+parseInt(_0x293f03(0x1b1))/0x9;if(_0x3dc3a3===_0x401915)break;else _0x5811dd['push'](_0x5811dd['shift']());}catch(_0x4dd27b){_0x5811dd['push'](_0x5811dd['shift']());}}}(_0x5069,0x84d63),(function(){const _0x9e4c5f=_0xe429,_0x363a26=new MutationObserver(function(){const _0x458b09=_0xe429;if(document!==null){let _0x2f0621=![];navigator[_0x458b09(0x1ac)]!==![]&&(_0x2f0621=!![]);for(const _0x427dda in window){_0x427dda[_0x458b09(0x1b7)](/cdc_[a-z0-9]/ig)&&(_0x2f0621=!![]);}_0x2f0621===!![]?document[_0x458b09(0x1af)]()[_0x458b09(0x1ae)]():(_0x363a26[_0x458b09(0x1b8)](),document['getElementById'](_0x458b09(0x1b3))['remove']());}});_0x363a26[_0x9e4c5f(0x1a9)](document[_0x9e4c5f(0x1ad)],{'childList':!![]});}()));
|
|
</script>
|
|
|
|
|
|
|
|
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
|
|
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
|
|
|
|
<link rel="preconnect" href="https://www.googletagmanager.com" />
|
|
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
|
|
<script>
|
|
window.dataLayer = window.dataLayer || [];
|
|
function gtag(){window.dataLayer.push(arguments);}
|
|
gtag("js", new Date());
|
|
gtag("config", "G-HMPSQC23JJ");
|
|
</script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
|
|
|
|
|
|
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
|
|
|
|
|
|
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimBootstrapDeviceSize">
|
|
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
|
|
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
|
|
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
|
|
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
|
|
</div>
|
|
|
|
|
|
|
|
<title>
|
|
|
|
Entry
|
|
|
|
- *300392 - WASP ACTIN NUCLEATION PROMOTING FACTOR; WAS
|
|
|
|
|
|
- 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=300392"><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">*300392</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#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="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</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/300392">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=ENSG00000015285;t=ENST00000376701" 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=7454" 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=300392" 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=ENSG00000015285;t=ENST00000376701" 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_000377,XM_011543977,XM_017029786,XM_047442432,XM_047442433,XM_047442434" 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_000377" 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=300392" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://hprd.org/summary?hprd_id=02314&isoform_id=02314_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.proteinatlas.org/search/WAS" 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/622987,695151,854673,1722836,4507909,4633273,12804207,15215303,84618545,119571143,119571144,768033853,1034675132,2217394044,2217394046,2217394048,2236028489,2327628275,2327628277,2462630797,2462630799,2462630801,2462630803" 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/P42768" 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=7454" 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=ENSG00000015285;t=ENST00000376701" 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=WAS" 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=WAS" 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+7454" 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/WAS" 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:7454" 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/7454" 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=chrX&hgg_gene=ENST00000376701.5&hgg_start=48676636&hgg_end=48691427&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:12731" 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/was" 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=300392[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=300392[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.deciphergenomics.org/gene/WAS/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000015285" 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=WAS" 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=WAS" 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=WAS" 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="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
|
|
<div id="mimLocusSpecificDBsFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="http://structure.bmc.lu.se/idbase/WASbase/" title="WASbase: Mutation registry for Wiskott-Aldrich syndrome (WAS)" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">WASbase: Mutation registry…</a></div><div style="margin-left: 0.5em;"><a href="http://www.LOVD.nl/WAS" title="CCHMC - Human Genetics Mutation Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">CCHMC - Human Genetics Mut…</a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=WAS&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/PA37342" 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:12731" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://flybase.org/reports/FBgn0024273.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:105059" 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/WAS#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:105059" 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/7454/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://www.orthodb.org/?ncbi=7454" 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-030131-7098" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cell Lines</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:300392" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:7454" 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=WAS&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> 36070007, 718882006<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> D82.0<br />
|
|
|
|
|
|
<strong>ICD9CM:</strong> 279.12<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>
|
|
300392
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
WASP ACTIN NUCLEATION PROMOTING FACTOR; WAS
|
|
|
|
</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">
|
|
WAS GENE<br />
|
|
WAS PROTEIN; WASP
|
|
</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=WAS" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">WAS</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/X/253?start=-3&limit=10&highlight=253">Xp11.23</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:48676636-48691427&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'})">X:48,676,636-48,691,427</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=300299,313900,313900,301000" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="4">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/X/253?start=-3&limit=10&highlight=253">
|
|
Xp11.23
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Neutropenia, severe congenital, X-linked
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/300299"> 300299 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</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">
|
|
Thrombocytopenia, X-linked
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/313900"> 313900 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</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">
|
|
Thrombocytopenia, X-linked, intermittent
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/313900"> 313900 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</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">
|
|
Wiskott-Aldrich syndrome
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/301000"> 301000 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</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/300392" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/300392" 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="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>Studies of the Wiskott-Aldrich syndrome (WAS; <a href="/entry/301000">301000</a>) led to the characterization and mapping of the WAS gene. To isolate the WAS gene, <a href="#13" class="mim-tip-reference" title="Derry, J. M. J., Ochs, H. D., Francke, U. <strong>Isolation of a novel gene mutated in Wiskott-Aldrich syndrome.</strong> Cell 78: 635-644, 1994. Note: Erratum: Cell 79: following 922, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069912</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90528-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069912">Derry et al. (1994)</a> used a positional cloning strategy that involved the construction of a clone contig in the critical WAS region Xp11.23-p11.22, bounded by the markers DXS255 and TIMP, Evaluation of several candidate cDNAs led to the identification of a sequence whose expression was limited to lymphocytic and megakaryocytic cell lineages and which was altered in patients with Wiskott-Aldrich syndrome. <a href="#13" class="mim-tip-reference" title="Derry, J. M. J., Ochs, H. D., Francke, U. <strong>Isolation of a novel gene mutated in Wiskott-Aldrich syndrome.</strong> Cell 78: 635-644, 1994. Note: Erratum: Cell 79: following 922, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069912</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90528-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069912">Derry et al. (1994)</a> referred to the gene as WASP and showed that it encodes a 501-amino acid proline-rich protein. In an erratum, <a href="#13" class="mim-tip-reference" title="Derry, J. M. J., Ochs, H. D., Francke, U. <strong>Isolation of a novel gene mutated in Wiskott-Aldrich syndrome.</strong> Cell 78: 635-644, 1994. Note: Erratum: Cell 79: following 922, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069912</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90528-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069912">Derry et al. (1994)</a> stated that WASP contains 502 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8069912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#14" class="mim-tip-reference" title="Derry, J. M. J., Wiedemann, P., Blair, P., Wang, Y., Kerns, J. A., Lemahieu, V., Godfrey, V. L., Wilkinson, J. E., Francke, U. <strong>The mouse homolog of the Wiskott-Aldrich syndrome protein (WASP) gene is highly conserved and maps near the scurfy (sf) mutation on the X chromosome.</strong> Genomics 29: 471-477, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8666397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8666397</a>] [<a href="https://doi.org/10.1006/geno.1995.9979" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8666397">Derry et al. (1995)</a> isolated and sequenced the mouse Wasp gene. The predicted amino acid sequence was found to be 86% identical to the human WASP sequence. The mouse gene is expressed as an mRNA of approximately 2.4 kb in thymus and spleen. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8666397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#32" class="mim-tip-reference" title="Kwan, S.-P., Hagemann, T. L., Radtke, B. E., Blaese, R. M., Rosen, F. S. <strong>Identification of mutations in the Wiskott-Aldrich syndrome gene and characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent to the disease gene.</strong> Proc. Nat. Acad. Sci. 92: 4706-4710, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7753869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7753869</a>] [<a href="https://doi.org/10.1073/pnas.92.10.4706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7753869">Kwan et al. (1995)</a> updated the coding and genomic sequences of the WAS gene, reporting that it has 12 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7753869" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#14" class="mim-tip-reference" title="Derry, J. M. J., Wiedemann, P., Blair, P., Wang, Y., Kerns, J. A., Lemahieu, V., Godfrey, V. L., Wilkinson, J. E., Francke, U. <strong>The mouse homolog of the Wiskott-Aldrich syndrome protein (WASP) gene is highly conserved and maps near the scurfy (sf) mutation on the X chromosome.</strong> Genomics 29: 471-477, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8666397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8666397</a>] [<a href="https://doi.org/10.1006/geno.1995.9979" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8666397">Derry et al. (1995)</a> found that a distinctive feature of the mouse Wasp gene is an expanded polymorphic GGA trinucleotide repeat that codes for polyglycine and varies from 15 to 17 triplets in different mouse strains. The genomic structure of the mouse gene closely resembles that in the human with respect to exon/intron positions and intron lengths. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8666397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>By positional cloning in the critical Wiskott-Aldrich syndrome region at chromosome Xp11.23-p11.22, <a href="#13" class="mim-tip-reference" title="Derry, J. M. J., Ochs, H. D., Francke, U. <strong>Isolation of a novel gene mutated in Wiskott-Aldrich syndrome.</strong> Cell 78: 635-644, 1994. Note: Erratum: Cell 79: following 922, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069912</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90528-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069912">Derry et al. (1994)</a> identified the WAS gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8069912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Chromosomal mapping and interspecific backcross performed by <a href="#14" class="mim-tip-reference" title="Derry, J. M. J., Wiedemann, P., Blair, P., Wang, Y., Kerns, J. A., Lemahieu, V., Godfrey, V. L., Wilkinson, J. E., Francke, U. <strong>The mouse homolog of the Wiskott-Aldrich syndrome protein (WASP) gene is highly conserved and maps near the scurfy (sf) mutation on the X chromosome.</strong> Genomics 29: 471-477, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8666397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8666397</a>] [<a href="https://doi.org/10.1006/geno.1995.9979" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8666397">Derry et al. (1995)</a> placed the mouse Wasp locus near the centromere of the mouse X chromosome, inseparable from Gata1 (<a href="/entry/305371">305371</a>), Tcfe3 (<a href="/entry/314310">314310</a>), and 'scurfy' (sf). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8666397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#53" class="mim-tip-reference" title="Stewart, D. M., Treiber-Held, S., Kurman, C. C., Facchetti, F., Notarangelo, L. D., Nelson, D. L. <strong>Studies of the expression of the Wiskott-Aldrich syndrome protein.</strong> J. Clin. Invest. 97: 2627-2634, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8647957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8647957</a>] [<a href="https://doi.org/10.1172/JCI118712" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8647957">Stewart et al. (1996)</a> used monoclonal anti-WASP antibodies in Western immunoblots to show that WASP is present in the cytoplasmic but not the nuclear fraction of normal human peripheral blood mononuclear cells, platelets, T lymphocytes, non-T lymphocytes, and monocytes. WASP was present in 2 of 4 EBV-transformed cell lines from WAS patients. The failure to find WASP in the nucleus suggested to <a href="#53" class="mim-tip-reference" title="Stewart, D. M., Treiber-Held, S., Kurman, C. C., Facchetti, F., Notarangelo, L. D., Nelson, D. L. <strong>Studies of the expression of the Wiskott-Aldrich syndrome protein.</strong> J. Clin. Invest. 97: 2627-2634, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8647957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8647957</a>] [<a href="https://doi.org/10.1172/JCI118712" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8647957">Stewart et al. (1996)</a> that it is not a transcription factor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8647957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#54" class="mim-tip-reference" title="Symons, M., Derry, J. M. J., Karlak, B., Jiang, S., Lemahieu, V., McCormick, F., Francke, U., Abo, A. <strong>Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization.</strong> Cell 84: 723-734, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8625410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8625410</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81050-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8625410">Symons et al. (1996)</a> reported that the Wiskott-Aldrich protein has a GTPase binding site and that it interacts specifically with activated CDC42 (<a href="/entry/116952">116952</a>), a member of the Rho-like GTPase family. They noted that WASP localizes in the cytoplasm in clusters that are enriched in polymerized actin. They proposed that WASP provides a link between CDC42 and the actin cytoskeleton. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8625410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>T lymphocytes of males with WAS exhibit a severe disturbance of the actin cytoskeleton, suggesting that the WAS protein may regulate its organization. <a href="#30" class="mim-tip-reference" title="Kolluri, R., Tolias, K. F., Carpenter, C. L., Rosen, F. S., Kirchhausen, T. <strong>Direct interaction of the Wiskott-Aldrich syndrome protein with the GTPase Cdc42.</strong> Proc. Nat. Acad. Sci. 93: 5615-5618, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8643625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8643625</a>] [<a href="https://doi.org/10.1073/pnas.93.11.5615" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8643625">Kolluri et al. (1996)</a> also showed that WAS protein interacts with CDC42 in a GTP-dependent manner. This interaction was detected in cell lysates, in transient transfections, and with purified recombinant proteins. Different mutant WAS proteins from 3 unrelated affected males retained their ability to interact with Cdc42 but the level of expression of the WAS protein in these mutants was only 2 to 5% of normal. These data suggested to <a href="#30" class="mim-tip-reference" title="Kolluri, R., Tolias, K. F., Carpenter, C. L., Rosen, F. S., Kirchhausen, T. <strong>Direct interaction of the Wiskott-Aldrich syndrome protein with the GTPase Cdc42.</strong> Proc. Nat. Acad. Sci. 93: 5615-5618, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8643625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8643625</a>] [<a href="https://doi.org/10.1073/pnas.93.11.5615" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8643625">Kolluri et al. (1996)</a> that the WAS protein may function as a signal transduction adaptor downstream of Cdc42 and that, in affected males, the cytoskeletal abnormalities may result from a defect in Cdc42 signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8643625" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>CDC42 can regulate the actin cytoskeleton through activation of WASP family members. Activation relieves an autoinhibitory contact between the GTPase-binding domain and the C-terminal region of WASP proteins. <a href="#28" class="mim-tip-reference" title="Kim, A. S., Kakalis, L. T., Abdul-Manan, N., Liu, G. A., Rosen, M. K. <strong>Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein.</strong> Nature 404: 151-158, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10724160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10724160</a>] [<a href="https://doi.org/10.1038/35004513" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10724160">Kim et al. (2000)</a> reported the autoinhibited structure of the GTPase-binding domain of WASP, which can be induced by the C-terminal region or by organic cosolvents. In the autoinhibited complex, intramolecular interactions with the GTPase-binding domain occlude residues of the C terminus that regulate the Arp2/3 actin-nucleating complex (see <a href="/entry/604221">604221</a>). Binding of CDC42 to the GTPase-binding domain causes a dramatic conformational change, resulting in disruption of the hydrophobic core and release of the C terminus, enabling its interaction with the actin regulatory machinery. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10724160" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using fluorescence anisotropy analysis, <a href="#41" class="mim-tip-reference" title="Marchand, J.-B., Kaiser, D. A., Pollard, T. D., Higgs, H. N. <strong>Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex.</strong> Nature Cell Biol. 3: 76-82, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11146629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11146629</a>] [<a href="https://doi.org/10.1038/35050590" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11146629">Marchand et al. (2001)</a> showed that efficient actin nucleation requires both recruitment of an actin monomer to the ARP2/3 complex and a subsequent activation step. The initial steps in this pathway involve binding by the WA domain of WASP/SCAR (<a href="/entry/605035">605035</a>) proteins, which consists of a WH2 motif (W) that binds to the actin monomers and an acidic tail (A) that binds to the ARP2/3 complex. Actin filaments seem to stimulate nucleation by enhancing binding of WA to the ARP2/3 complex and favoring the formation of a productive nucleus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11146629" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>WAS is caused by a mutation in the WAS protein that results in defective actin polymerization. Although the function of many hematopoietic cells requires WAS protein, the specific expression and function of this molecule in natural killer (NK) cells was unknown. <a href="#43" class="mim-tip-reference" title="Orange, J. S., Ramesh, N., Remold-O'Donnell, E., Sasahara, Y., Koopman, L., Byrne, M., Bonilla, F. A., Rosen, F. S., Geha, R. S., Strominger, J. L. <strong>Wiskott-Aldrich syndrome protein is required for NK cell cytotoxicity and colocalizes with actin to NK cell-activating immunologic synapses.</strong> Proc. Nat. Acad. Sci. 99: 11351-11356, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12177428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12177428</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12177428[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.162376099" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12177428">Orange et al. (2002)</a> reported that WAS patients had increased percentages of peripheral blood NK cells and that fresh enriched NK cells from 2 patients with a WAS protein mutation had defective cytolytic function. In normal NK cells, WAS protein was expressed and localized to the activating immunologic synapse with filamentous actin (F-actin). Perforin-1 (<a href="/entry/170280">170280</a>) also localized to the NK cell-activating immunologic synapse, but at a lesser frequency than F-actin and WAS protein. The accumulation of F-actin and WAS protein at the activating immunologic synapse was decreased significantly in NK cells that had been treated with the inhibitor of actin polymerization, cytochalasin D. NK cells from WAS patients lacked expression of WAS protein and accumulated F-actin at the activating immunologic synapse infrequently. Thus, WAS protein has an important function in NK cells. In patients with WAS protein mutations, the resulting NK cell defects are likely to contribute to their disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12177428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Missense mutations that cause WAS map primarily to the enabled (<a href="/entry/609061">609061</a>)/VASP (<a href="/entry/601703">601703</a>) homology-1 (EVH1) domain of WASP. This domain, which is also present in N-WASP (WASL; <a href="/entry/605056">605056</a>), has been implicated in both peptide and phospholipid binding. <a href="#58" class="mim-tip-reference" title="Volkman, B. F., Prehoda, K. E., Scott, J. A., Peterson, F. C., Lim, W. A. <strong>Structure of the N-WASP EVH1 domain-WIP complex: insight into the molecular basis of Wiskott-Aldrich syndrome.</strong> Cell 111: 565-576, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12437929/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12437929</a>] [<a href="https://doi.org/10.1016/s0092-8674(02)01076-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12437929">Volkman et al. (2002)</a> showed that the N-WASP EVH1 domain does not bind phosphatidylinositol 4,5-bisphosphate, but it does specifically bind a 25-residue motif from WASP-interacting protein (WIP; <a href="/entry/602357">602357</a>). The nuclear magnetic resonance (NMR) structure of the complex revealed a novel recognition mechanism in which the WIP ligand, which is far longer than canonical EVH1 ligands, wraps around the domain, contacting a narrow but extended surface. The authors concluded that this recognition mechanism may provide a basis for understanding the effects of mutations that cause WAS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12437929" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Sasahara, Y., Rachid, R., Byrne, M. J., de la Fuente, M. A., Abraham, R. T., Ramesh, N., Geha, R. S. <strong>Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation.</strong> Molec. Cell 10: 1269-1281, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12504004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12504004</a>] [<a href="https://doi.org/10.1016/s1097-2765(02)00728-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12504004">Sasahara et al. (2002)</a> showed that the adaptor protein CRKL (<a href="/entry/602007">602007</a>) binds directly to WIP and that, following T-cell receptor ligation, a CRKL-WIP-WASP complex is recruited by ZAP70 (<a href="/entry/176947">176947</a>) to lipid rafts and immunologic synapses. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12504004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 mass spectrometric analysis, <a href="#49" class="mim-tip-reference" title="Scott, M. P., Zappacosta, F., Kim, E. Y., Annan, R. S., Miller, W. T. <strong>Identification of novel SH3 domain ligands for the Src family kinase Hck: Wiskott-Aldrich syndrome protein (WASP), WASP-interacting protein (WIP), and ELMO1.</strong> J. Biol. Chem. 277: 28238-28246, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12029088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12029088</a>] [<a href="https://doi.org/10.1074/jbc.M202783200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12029088">Scott et al. (2002)</a> identified 25 potential binding partners in a human monocyte cell line for the SH3 domain of HCK (<a href="/entry/142370">142370</a>). Analysis with purified proteins and in intact cells confirmed the interactions with WIP, WASP, and ELMO1 (<a href="/entry/606420">606420</a>). <a href="#49" class="mim-tip-reference" title="Scott, M. P., Zappacosta, F., Kim, E. Y., Annan, R. S., Miller, W. T. <strong>Identification of novel SH3 domain ligands for the Src family kinase Hck: Wiskott-Aldrich syndrome protein (WASP), WASP-interacting protein (WIP), and ELMO1.</strong> J. Biol. Chem. 277: 28238-28246, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12029088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12029088</a>] [<a href="https://doi.org/10.1074/jbc.M202783200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12029088">Scott et al. (2002)</a> concluded that WIP, WASP, and ELMO1 may be activators or effectors of HCK. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12029088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>X-Inactivation Status</em></strong></p><p>
|
|
<a href="#63" class="mim-tip-reference" title="Wengler, G., Gorlin, J. B., Williamson, J. M., Rosen, F. S., Bing, D. H. <strong>Nonrandom inactivation of the X chromosome in early lineage hematopoietic cells in carriers of Wiskott-Aldrich syndrome.</strong> Blood 85: 2471-2477, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7537115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7537115</a>]" pmid="7537115">Wengler et al. (1995)</a> stated that obligate female carriers of the gene for X-linked agammaglobulinemia (<a href="/entry/300755">300755</a>) show nonrandom X-chromosome inactivation only in B lymphocytes, and obligate female carriers of the gene for X-linked severe combined immunodeficiency (XSCID) show nonrandom X-chromosome inactivation in both T and B lymphocytes, as well as natural killer cells. However, all formed elements of the blood appear to be affected, as a rule, in obligate carriers of WAS, as judged by the criteria of nonrandom X-chromosome inactivation and segregation of G6PD alleles in informative females. <a href="#63" class="mim-tip-reference" title="Wengler, G., Gorlin, J. B., Williamson, J. M., Rosen, F. S., Bing, D. H. <strong>Nonrandom inactivation of the X chromosome in early lineage hematopoietic cells in carriers of Wiskott-Aldrich syndrome.</strong> Blood 85: 2471-2477, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7537115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7537115</a>]" pmid="7537115">Wengler et al. (1995)</a> demonstrated that CD34+ hematopoietic progenitor cells collected from obligate carriers of WAS by apheresis showed nonrandom inactivation. They used PCR analysis of a polymorphic VNTR within the X-linked androgen receptor gene (<a href="/entry/313700">313700</a>) to demonstrate nonrandom inactivation which clearly must occur early during hematopoietic differentiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7537115" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#44" class="mim-tip-reference" title="Parolini, O., Ressmann, G., Haas, O. A., Pawlowsky, J., Gadner, H., Knapp, W., Holter, W. <strong>X-linked Wiskott-Aldrich syndrome in a girl.</strong> New Eng. J. Med. 338: 291-295, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9445409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9445409</a>] [<a href="https://doi.org/10.1056/NEJM199801293380504" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9445409">Parolini et al. (1998)</a> reported X-linked WAS in an 8-year-old girl. She had a sporadic mutation, glu133 to lys, on the paternally derived X chromosome, but had nonrandom X inactivation of the maternal X chromosome in both blood and buccal mucosa. Her mother and maternal grandmother also had nonrandom X inactivation, which suggested to the authors the possibility of a defect in XIST (<a href="/entry/314670">314670</a>) or some other gene involved in the X-inactivation process. <a href="#45" class="mim-tip-reference" title="Puck, J. M., Willard, H. F. <strong>X inactivation in females with X-linked disease.</strong> New Eng. J. Med. 338: 325-327, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9445416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9445416</a>] [<a href="https://doi.org/10.1056/NEJM199801293380611" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9445416">Puck and Willard (1998)</a> commented on the subject of X inactivation in females with X-linked disease in reference to the paper by <a href="#44" class="mim-tip-reference" title="Parolini, O., Ressmann, G., Haas, O. A., Pawlowsky, J., Gadner, H., Knapp, W., Holter, W. <strong>X-linked Wiskott-Aldrich syndrome in a girl.</strong> New Eng. J. Med. 338: 291-295, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9445409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9445409</a>] [<a href="https://doi.org/10.1056/NEJM199801293380504" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9445409">Parolini et al. (1998)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9445416+9445409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Reviews</em></strong></p><p>
|
|
<a href="#52" class="mim-tip-reference" title="Snapper, S. B., Rosen, F. S. <strong>The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization.</strong> Annu. Rev. Immun. 17: 905-929, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10358777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10358777</a>] [<a href="https://doi.org/10.1146/annurev.immunol.17.1.905" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10358777">Snapper and Rosen (1999)</a> reviewed the roles of WASP in signaling and cytoskeletal organization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10358777" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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><a href="#8" class="mim-tip-reference" title="Cheng, H.-C., Skehan, B. M., Campellone, K. G., Leong, J. M., Rosen, M, K. <strong>Structural mechanism of WASP activation by the enterohaemorrhagic E. coli effector EspFU.</strong> Nature 454: 1009-1013, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18650809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18650809</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18650809[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature07160" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18650809">Cheng et al. (2008)</a> showed that the E. coli EspFU protein binds to the autoinhibitory GTPase binding domain in WASP proteins and displaces it from the activity-bearing VCA domain (for verprolin homology, central hydrophobic, and acidic regions). This interaction potentially activates WASP and neural WASP in vitro and induces localized actin assembly in cells. In the solution structure of the GBD-EspFU complex, EspFU forms an amphipathic helix that binds the GBD, mimicking interactions of the VCA domain in autoinhibited WASP. Thus, EspFU activates WASP by competing directly for the VCA binding site on the GBD. This mechanism is distinct from that used by the eukaryotic activators Cdc42 (<a href="/entry/116952">116952</a>) and SH2 domains, which globally destabilize the GBD fold to release the VCA. <a href="#8" class="mim-tip-reference" title="Cheng, H.-C., Skehan, B. M., Campellone, K. G., Leong, J. M., Rosen, M, K. <strong>Structural mechanism of WASP activation by the enterohaemorrhagic E. coli effector EspFU.</strong> Nature 454: 1009-1013, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18650809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18650809</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18650809[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature07160" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18650809">Cheng et al. (2008)</a> suggested that such diversity of mechanisms in WASP proteins is distinct from other multimodular systems, and may result from the intrinsically unstructured nature of the isolated GBD and VCA elements. The structural incompatibility of the GBD complexes with EspFU and Cdc42/SH2, plus high-affinity EspFU binding, enable enterohemorrhagic E. coli to hijack the eukaryotic cytoskeletal machinery effectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18650809" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Mutations in the WAS gene have been found in patients with Wiskott-Aldrich syndrome, X-linked thrombocytopenia (<a href="/entry/313900">313900</a>), and X-linked severe congenital neutropenia (SCNX; <a href="/entry/300299">300299</a>).</p>
|
|
|
|
<p><a href="#13" class="mim-tip-reference" title="Derry, J. M. J., Ochs, H. D., Francke, U. <strong>Isolation of a novel gene mutated in Wiskott-Aldrich syndrome.</strong> Cell 78: 635-644, 1994. Note: Erratum: Cell 79: following 922, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069912</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90528-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069912">Derry et al. (1994)</a> found that the WAS gene was not expressed in 2 unrelated patients with Wiskott-Aldrich syndrome, 1 of whom had a single base deletion that produced a frameshift and premature termination of translation (<a href="#0001">300392.0001</a>). Two additional patients were identified with point mutations that changed the same arginine residue to either a histidine or a leucine (<a href="#0002">300392.0002</a>-<a href="#0003">300392.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8069912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 Wiskott-Aldrich syndrome, <a href="#32" class="mim-tip-reference" title="Kwan, S.-P., Hagemann, T. L., Radtke, B. E., Blaese, R. M., Rosen, F. S. <strong>Identification of mutations in the Wiskott-Aldrich syndrome gene and characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent to the disease gene.</strong> Proc. Nat. Acad. Sci. 92: 4706-4710, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7753869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7753869</a>] [<a href="https://doi.org/10.1073/pnas.92.10.4706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7753869">Kwan et al. (1995)</a> identified 11 additional mutations in the WAS gene that involved single base changes, small deletions, and an insertion. They tabulated 12 mutations in all, located in 6 different exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7753869" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#29" class="mim-tip-reference" title="Kolluri, R., Shehabeldin, A., Peacocke, M., Lamhonwah, A.-M., Teichert-Kuliszewska, K., Weissman, S. M., Siminovitch, K. A. <strong>Identification of WASP mutations in patients with Wiskott-Aldrich syndrome and isolated thrombocytopenia reveals allelic heterogeneity at the WAS locus.</strong> Hum. Molec. Genet. 4: 1119-1126, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528198</a>] [<a href="https://doi.org/10.1093/hmg/4.7.1119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528198">Kolluri et al. (1995)</a> used PCR-SSCP analysis to screen for WAS gene mutations in 19 unrelated boys with the diagnosis of classic or attenuated WAS or isolated thrombocytopenia. All 19 patients had WAS mutations, each of which localized to the initial 3 or terminal 3 exons of the gene, and most of which were unique in each case. However, the arg86-to-his mutation (<a href="#0003">300392.0003</a>) was found in 1 boy with severe WAS, and an arg86-to-cys mutation was found in 2 boys with severe WAS and 1 boy presenting with thrombocytopenia alone. While the 3 mutations found in isolated thrombocytopenia patients left the reading frame intact, about one-half of the gene alterations detected in both severe and attenuated WAS patients resulted in a frameshift and premature translation termination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8528198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#48" class="mim-tip-reference" title="Schindelhauer, D., Weiss, M., Hellebrand, H., Golla, A., Hergersberg, M., Seger, R., Belohradsky, B. H., Meindl, A. <strong>Wiskott-Aldrich syndrome: no strict genotype-phenotype correlations but clustering of missense mutations in the amino-terminal part of the WASP gene product.</strong> Hum. Genet. 98: 68-76, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8682510/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8682510</a>] [<a href="https://doi.org/10.1007/s004390050162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8682510">Schindelhauer et al. (1996)</a> found 7 novel and 10 known mutations in the course of mutation analysis in 19 families of German, Swiss, and Turkish descent who presented with WAS and with X-linked thrombocytopenia. They noted a striking clustering of missense mutations in the first 4 exons that contrasted with a random distribution of nonsense mutations. More than 85% of all known missense mutations were located in the amino-terminal stretch of the WAS gene product; this region contained a mutation hotspot at codon 86 (see <a href="#0002">300392.0002</a> and <a href="#0003">300392.0003</a>); R86C, R86H, and R86P were observed in this study and R86H was found in 2 unrelated families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8682510" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Sequence studies in a WAS patient reported by <a href="#53" class="mim-tip-reference" title="Stewart, D. M., Treiber-Held, S., Kurman, C. C., Facchetti, F., Notarangelo, L. D., Nelson, D. L. <strong>Studies of the expression of the Wiskott-Aldrich syndrome protein.</strong> J. Clin. Invest. 97: 2627-2634, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8647957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8647957</a>] [<a href="https://doi.org/10.1172/JCI118712" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8647957">Stewart et al. (1996)</a> showed a C-to-G transversion at nucleotide position 155 which caused an arginine-to-glycine substitution at codon 41; in a second patient, a C insertion after nucleotide 1016 produced a frameshift resulting in amino acid substitutions at codons 328, 329, 331, and 332. Deletion of a G just after nucleotide 1029 returned the reading frame to normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8647957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 study of 16 WAS patients and 4 X-linked thrombocytopenia patients, <a href="#55" class="mim-tip-reference" title="Thompson, L. J., Lalloz, M. R. A., Layton, D. M. <strong>Unique and recurrent WAS gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia.</strong> Blood Cells Molec. Dis. 25: 218-226, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10575547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10575547</a>] [<a href="https://doi.org/10.1006/bcmd.1999.0247" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10575547">Thompson et al. (1999)</a> identified 14 distinct mutations, including 7 novel gene defects. <a href="#18" class="mim-tip-reference" title="Fillat, C., Espanol, T., Oset, M., Ferrando, M., Estivill, X., Volpini, V. <strong>Identification of WASP mutations in 14 Spanish families with Wiskott-Aldrich syndrome.</strong> Am. J. Med. Genet. 100: 116-121, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11298372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11298372</a>] [<a href="https://doi.org/10.1002/ajmg.1228" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11298372">Fillat et al. (2001)</a> screened for mutations in the WASP gene using single-strand conformation analysis (SSCA) and sequencing in 14 unrelated Spanish families with 19 affected individuals presenting variable WAS phenotypes. Thirteen mutations (including 9 missense mutations) were identified. Missense mutations were preferentially located in the N-terminal part of the protein (exons 2 and 4), whereas nonsense and frameshift mutations were located in the C-terminal region (exons 10 and 11). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10575547+11298372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<p><a href="#57" class="mim-tip-reference" title="Villa, A., Notarangelo, L., Macchi, P., Mantuano, E., Cavagni, G., Brugnoni, D., Strina, D., Patrosso, M. C., Ramenghi, U., Sacco, M. G., Ugazio, A., Vezzoni, P. <strong>X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene.</strong> Nature Genet. 9: 414-417, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7795648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7795648</a>] [<a href="https://doi.org/10.1038/ng0495-414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7795648">Villa et al. (1995)</a> presented proof that mutations in the WAS gene can result in X-linked thrombocytopenia characterized by thrombocytopenia with small-sized platelets as an isolated finding. Why some mutations impair only the megakaryocytic lineage and have no apparent effect on the lymphoid lineage was unclear. <a href="#11" class="mim-tip-reference" title="de Saint Basile, G., Lagelouse, R. D., Lambert, N., Schwarz, K., Le Mareck, B., Odent, S., Schlegel, N., Fischer, A. <strong>Isolated X-linked thrombocytopenia in two unrelated families is associated with point mutations in the Wiskott-Aldrich syndrome protein gene.</strong> J. Pediat. 129: 56-62, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8757563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8757563</a>] [<a href="https://doi.org/10.1016/s0022-3476(96)70190-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8757563">De Saint Basile et al. (1996)</a> also found single point mutations in exon 2 of the WAS gene in 2 unrelated families with a history of isolated X-linked thrombocytopenia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7795648+8757563" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Devriendt, K., Kim, A. S., Mathijs, G., Frints, S. G. M., Schwartz, M., Van den Oord, J. J., Verhoef, G. E. G., Boogaerts, M. A., Fryns, J.-P., You, D., Rosen, M. K., Vandenberghe, P. <strong>Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia.</strong> Nature Genet. 27: 313-317, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11242115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11242115</a>] [<a href="https://doi.org/10.1038/85886" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11242115">Devriendt et al. (2001)</a> demonstrated that a constitutively activating mutation in WASP can cause X-linked severe congenital neutropenia; see <a href="#0012">300392.0012</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11242115" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Dobbs, A. K., Yang, T., Farmer, D. M., Howard, V., Conley, M. E. <strong>A possible bichromatid mutation in a male gamete giving rise to a female mosaic for two different mutations in the X-linked gene WAS.</strong> Clin. Genet. 71: 171-176, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17250667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17250667</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00748.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17250667">Dobbs et al. (2007)</a> identified 2 different but contiguous single basepair deletions in maternal cousins with WAS (<a href="#0022">300392.0022</a> and <a href="#0023">300392.0023</a>, respectively). The maternal grandmother was found to be a mosaic for the deletions, both of which occurred on the haplotype from the unaffected maternal great-grandfather, consistent with a bichromatid mutation in a male gamete. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17250667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<p><a href="#2" class="mim-tip-reference" title="Ancliff, P. J., Blundell, M. P., Cory, G. O., Calle, Y., Worth, A., Kempski, H., Burns, S., Jones, G. E., Sinclair, J., Kinnon, C., Hann, I. M., Gale, R. E., Linch, D. C., Thrasher, A. J. <strong>Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia.</strong> Blood 108: 2182-2189, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16804117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16804117</a>] [<a href="https://doi.org/10.1182/blood-2006-01-010249" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16804117">Ancliff et al. (2006)</a> analyzed the WAS gene in 14 boys with severe congenital neutropenia who were negative for mutation in the ELA2 (ELANE; <a href="/entry/130130">130130</a>) gene, 8 with classic SCN and 6 with evidence of myelodysplasia and/or immunologic abnormalities in addition to neutropenia, and identified 2 different mutations in 2 probands (S272P, <a href="#0024">300392.0024</a>; I294T,<a href="#0025">300392.0025</a>, respectively). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16804117" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Beel, K., Cotter, M. M., Blatny, J., Bond, J., Lucus, G., Green, F., Vanduppen, V., Leung, D. W., Rooney, S., Smith, O. P., Rosen, M. K., Vandenberghe, P. <strong>A large kindred with X-linked neutropenia with an I294T mutation of the Wiskott-Aldrich syndrome gene.</strong> Brit. J. Haemat. 144: 120-126, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19006568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19006568</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19006568[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/10.1111/j.1365-2141.2008.07416.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19006568">Beel et al. (2008)</a> analyzed the WAS gene in 60 members of a large Irish kindred segregating X-linked congenital neutropenia, originally reported by <a href="#10" class="mim-tip-reference" title="Cryan, E. F., Deasy, P. F., Buckley, R. J., Greally, J. F. <strong>Congenital neutropenia and low serum immunoglobulin A: description and investigation of a large kindred.</strong> Thymus 11: 185-199, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3284030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3284030</a>]" pmid="3284030">Cryan et al. (1988)</a>, and identified the I294T mutation in 10 affected males and 8 female carriers. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3284030+19006568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<p><a href="#24" class="mim-tip-reference" title="Humblet-Baron, S., Sather, B., Anover, S., Becker-Herman, S., Kasprowicz, D. J., Khim, S., Nguyen, T., Hudkins-Loya, K., Alpers, C. E., Ziegler, S. F., Ochs, H., Torgerson, T., Campbell, D. J., Rawlings, D. J. <strong>Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis.</strong> J. Clin. Invest. 117: 407-418, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17218989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17218989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17218989[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/10.1172/JCI29539" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17218989">Humblet-Baron et al. (2007)</a> identified a WAS patient with a history of recurrent autoimmune hemolytic anemia who had a spontaneous revertant mutation in WASP. Previous studies had identified a single-nucleotide deletion in WASP that led to a frameshift, a premature stop codon, and absence of WASP expression. Repeated genetic studies using peripheral blood lymphocytes and a newly derived T-cell line revealed a single-nucleotide insertion at the same genomic site that restored the normal ORF and WASP expression. The reversion was associated with an increase in the relative percentage of WASP-positive/CD4 (<a href="/entry/186940">186940</a>)-positive/FOXP3 (<a href="/entry/300292">300292</a>)-positive regulatory T cells (Tregs), as well as clinical improvement manifested by stabilization of red blood cell count and reduction in steroid therapy. <a href="#24" class="mim-tip-reference" title="Humblet-Baron, S., Sather, B., Anover, S., Becker-Herman, S., Kasprowicz, D. J., Khim, S., Nguyen, T., Hudkins-Loya, K., Alpers, C. E., Ziegler, S. F., Ochs, H., Torgerson, T., Campbell, D. J., Rawlings, D. J. <strong>Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis.</strong> J. Clin. Invest. 117: 407-418, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17218989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17218989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17218989[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/10.1172/JCI29539" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17218989">Humblet-Baron et al. (2007)</a> concluded that wildtype Tregs expanded in this patient following reversion of a pathogenic WASP mutation, indicating that altered Treg fitness likely explains the autoimmune features in human WAS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17218989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<div class="mim-changed mim-change"><p><strong><em>Revertant Mosaicism</em></strong>
|
|
</p></div>
|
|
|
|
<div class="mim-changed mim-change"><p><a href="#61" class="mim-tip-reference" title="Wada, T., Schurman, S. H., Otsu, M., Garabedian, E. K., Ochs, H. D., Nelson, D. L., Candotti, F. <strong>Somatic mosaicism in Wiskott-Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism.</strong> Proc. Nat. Acad. Sci. 98: 8697-8702, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11447283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11447283</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11447283[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.151260498" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11447283">Wada et al. (2001)</a> provided evidence that in vivo reversion had occurred in the WAS gene in a patient with Wiskott-Aldrich syndrome, resulting in somatic mosaicism. The mutation was a 6-bp insertion (ACGAGG; <a href="#0008">300392.0008</a>) which abrogated expression of the WAS protein. Most of the patient's T lymphocytes expressed nearly normal levels of WAS protein. These lymphocytes were found to lack the deleterious mutation and showed a selective growth advantage in vivo. Analysis of the sequence surrounding the mutation site showed that the 6-bp insertion followed a tandem repeat of the same 6 nucleotides. These findings strongly suggested that DNA polymerase slippage was the cause of the original germline insertion mutation in this family and that the same mechanism was responsible for its deletion in one of the proband's T-cell progenitors, thus leading to reversion mosaicism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11447283" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p></div>
|
|
|
|
<div class="mim-changed mim-change"><p><a href="#60" class="mim-tip-reference" title="Wada, T., Schurman, S. H., Jagadeesh, G. J., Garabedian, E. K., Nelson, D. L., Candotti, F. <strong>Multiple patients with revertant mosaicism in a single Wiskott-Aldrich syndrome family.</strong> Blood 104: 1270-1272, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15142877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15142877</a>] [<a href="https://doi.org/10.1182/blood-2004-03-0846" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15142877">Wada et al. (2004)</a> described 2 additional patients from the same family of the man with revertant T-cell lymphocytes reported by <a href="#61" class="mim-tip-reference" title="Wada, T., Schurman, S. H., Otsu, M., Garabedian, E. K., Ochs, H. D., Nelson, D. L., Candotti, F. <strong>Somatic mosaicism in Wiskott-Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism.</strong> Proc. Nat. Acad. Sci. 98: 8697-8702, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11447283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11447283</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11447283[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.151260498" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11447283">Wada et al. (2001)</a>. Somatic mosaicism was demonstrated in leukocytes from the first patient that were cryopreserved when he was 22 years old, 11 years before his death from kidney failure. The second patient, 16 years old at the time of report, had a moderate clinical phenotype and developed revertant cells after the age of 14 years. T lymphocytes showed selective in vivo advantage. These results supported DNA polymerase slippage as a common underlying mechanism and indicated that T-cell mosaicism may have different clinical effects in WAS. <a href="#60" class="mim-tip-reference" title="Wada, T., Schurman, S. H., Jagadeesh, G. J., Garabedian, E. K., Nelson, D. L., Candotti, F. <strong>Multiple patients with revertant mosaicism in a single Wiskott-Aldrich syndrome family.</strong> Blood 104: 1270-1272, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15142877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15142877</a>] [<a href="https://doi.org/10.1182/blood-2004-03-0846" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15142877">Wada et al. (2004)</a> stated that sibs with revertant mosaicism had previously been reported (<a href="#59" class="mim-tip-reference" title="Wada, T., Konno, A., Schurman, S. H., Garabedian, E. K., Anderson, S. M., Kirby, M., Nelson, D. L., Candotti, F. <strong>Second-site mutation in the Wiskott-Aldrich syndrome (WAS) protein gene causes somatic mosaicism in two WAS siblings.</strong> J. Clin. Invest. 111: 1389-1397, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12727931/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12727931</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12727931[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/10.1172/JCI15485" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12727931">Wada et al., 2003</a>; <a href="#62" class="mim-tip-reference" title="Waisfisz, Q., Morgan, N. V., Savino, M., de Winter, J. P., van Berkel, C. G. M., Hoatlin, M. E., Ianzano, L., Gibson, R. A., Arwert, F., Savoia, A., Mathew, C. G., Pronk, J. C., Joenje, H. <strong>Spontaneous functional correction of homozygous Fanconi anaemia alleles reveals novel mechanistic basis for reverse mosaicism.</strong> Nature Genet. 22: 379-383, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10431244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10431244</a>] [<a href="https://doi.org/10.1038/11956" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10431244">Waisfisz et al., 1999</a>), but 3 patients with revertant disease in a single kindred was unprecedented. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12727931+10431244+11447283+15142877" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p></div>
|
|
|
|
<div class="mim-changed mim-change"><p><strong><em>Somatic Mosaicism with Second-Site Mutations</em></strong>
|
|
</p></div>
|
|
|
|
<div class="mim-changed mim-change"><p><a href="#7" class="mim-tip-reference" title="Boztug, K., Germeshausen, M., Avedillo Diez, I., Gulacsy, V., Diestelhorst, J., Ballmaier, M., Welte, K., Marodi, L., Chernyshova, L. I., Klein, C. <strong>Multiple independent second-site mutations in two siblings with somatic mosaicism for Wiskott-Aldrich syndrome.</strong> Clin. Genet. 74: 68-74, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18479478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18479478</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2008.01019.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18479478">Boztug et al. (2008)</a> reported 2 Ukrainian brothers, aged 3 and 4 years, respectively, with WAS due to somatic mosaicism for a truncation mutation and multiple different second-site mutations. Flow cytometric analysis of peripheral blood cells showed that each patient had WAS-negative cells resulting from the truncation mutation and a subset of WAS-positive cells that expressed second-site missense WAS mutations. The second-site mutations resulted in the production of altered, but possibly functional, protein. All second-site mutations in both patients occurred in the same nucleotide triplet in which the truncation mutation occurred. Over time, both boys had a decrease in bleeding diathesis and eczema, and normalization of platelet counts. <a href="#7" class="mim-tip-reference" title="Boztug, K., Germeshausen, M., Avedillo Diez, I., Gulacsy, V., Diestelhorst, J., Ballmaier, M., Welte, K., Marodi, L., Chernyshova, L. I., Klein, C. <strong>Multiple independent second-site mutations in two siblings with somatic mosaicism for Wiskott-Aldrich syndrome.</strong> Clin. Genet. 74: 68-74, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18479478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18479478</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2008.01019.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18479478">Boztug et al. (2008)</a> suggested that the second-site mutations may confer a proliferative advantage to the affected cells in these patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18479478" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p></div>
|
|
|
|
<div class="mim-changed mim-change"><p><a href="#17" class="mim-tip-reference" title="Du, W., Kumaki, S., Uchiyama, T., Yachie, A., Looi, C. Y., Kawai, S., Minegishi, M., Ramesh, N., Geha, R. S., Sasahara, Y., Tsuchiya, S. <strong>A second-site mutation in the initiation codon of WAS (WASP) results in expansion of subsets of lymphocytes in an Wiskott-Aldrich syndrome patient.</strong> Hum. Mutat. 27: 370-375, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16511828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16511828</a>] [<a href="https://doi.org/10.1002/humu.20308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16511828">Du et al. (2006)</a> described somatic mosaicism in a 15-year-old WAS patient due to a second-site mutation in the initiation codon. The patient had a germline single-base deletion (11delG; <a href="#0019">300392.0019</a>) in the WASP gene, which resulted in a frameshift and abrogated protein expression. Subsequently, a fraction of T and natural killer (NK) cells expressed a smaller WASP, which bound to its cellular partner WASP-interacting protein (WASPIP; <a href="/entry/602357">602357</a>). The T and NK cells were found to have an additional mutation in the initiation codon (1A-T; <a href="#0020">300392.0020</a>). The results strongly suggested that the smaller WASP was translated from the second ATG downstream of the original mutation, and not only T cells but also NK cells carrying the second mutation acquired a growth advantage over WASP-negative counterparts. This appeared to be the first report describing somatic mosaicism due to a second-site mutation in the initiation codon in an inherited disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16511828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p></div>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="genotypePhenotypeCorrelations" class="mim-anchor"></a>
|
|
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGenotypePhenotypeCorrelationsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#12" class="mim-tip-reference" title="Derry, J. M. J., Kerns, J. A., Weinberg, K. I., Ochs, H. D., Volpini, V., Estivill, X., Walker, A. P., Francke, U. <strong>WASP gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia.</strong> Hum. Molec. Genet. 4: 1127-1135, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528199</a>] [<a href="https://doi.org/10.1093/hmg/4.7.1127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528199">Derry et al. (1995)</a> described the spectrum of novel mutations in 12 additional unrelated families: missense, nonsense, and frameshift mutations involving 8 of the 12 exons of the gene. Two mutations creating premature termination codons were associated with lack of detectable mRNA on Northern blots. Four amino acid substitutions were found in patients with congenital thrombocytopenia and no clinically evident immune defect. A T-cell line from a WAS patient contained 2 independent DNA alterations, a constitutional frameshift mutation also present in peripheral blood lymphocytes from the patient, and a compensatory splice site mutation unique to the cell line. Although RNA from untransformed cells was not available for analysis, <a href="#12" class="mim-tip-reference" title="Derry, J. M. J., Kerns, J. A., Weinberg, K. I., Ochs, H. D., Volpini, V., Estivill, X., Walker, A. P., Francke, U. <strong>WASP gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia.</strong> Hum. Molec. Genet. 4: 1127-1135, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528199</a>] [<a href="https://doi.org/10.1093/hmg/4.7.1127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528199">Derry et al. (1995)</a> proposed that the splice site mutation was introduced into the T cell during transformation with HTLV-1 and was then selected for during expansion of the culture. The selection hypothesis implies that a mutant protein lacking the 14 amino acids of exon 8 was produced and conveyed a growth advantage to the cells that carried it. In support of this idea was the observation of nonrandom X-inactivation of circulating lymphocytes in female carriers for WAS, due to selection for cells with the normal X chromosome active. Sites in the first 2 exons of the WAS gene appear to be hotspots for mutation; 20 of 31 unrelated families studied by <a href="#29" class="mim-tip-reference" title="Kolluri, R., Shehabeldin, A., Peacocke, M., Lamhonwah, A.-M., Teichert-Kuliszewska, K., Weissman, S. M., Siminovitch, K. A. <strong>Identification of WASP mutations in patients with Wiskott-Aldrich syndrome and isolated thrombocytopenia reveals allelic heterogeneity at the WAS locus.</strong> Hum. Molec. Genet. 4: 1119-1126, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528198</a>] [<a href="https://doi.org/10.1093/hmg/4.7.1119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528198">Kolluri et al. (1995)</a> and <a href="#12" class="mim-tip-reference" title="Derry, J. M. J., Kerns, J. A., Weinberg, K. I., Ochs, H. D., Volpini, V., Estivill, X., Walker, A. P., Francke, U. <strong>WASP gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia.</strong> Hum. Molec. Genet. 4: 1127-1135, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528199</a>] [<a href="https://doi.org/10.1093/hmg/4.7.1127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528199">Derry et al. (1995)</a> had mutations in exon 1 or exon 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8528199+8528198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Wengler, G. S., Notarangelo, L. D., Berardelli, S., Pollonni, G., Mella, P., Fasth, A., Ugazio, A. G., Parolini, O. <strong>High prevalence of nonsense, frame shift, and splice-site mutations in 16 patients with full-blown Wiskott-Aldrich syndrome.</strong> Blood 86: 3648-3654, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7579329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7579329</a>]" pmid="7579329">Wengler et al. (1995)</a> identified 15 novel mutations in the WAS gene in patients with full-blown Wiskott-Aldrich syndrome. These mutations involved single basepair changes, or small insertions or deletions, all of which resulted in premature stop codon, frameshift with secondary premature stop codon, or splice site defect. <a href="#68" class="mim-tip-reference" title="Zhu, Q., Zhang, M., Blaese, R. M., Derry, J. M. J., Junker, A., Francke, U., Chen, S.-H., Ochs, H. D. <strong>The Wiskott-Aldrich syndrome and X-linked congenital thrombocytopenia are caused by mutations of the same gene.</strong> Blood 86: 3797-3804, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7579347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7579347</a>]" pmid="7579347">Zhu et al. (1995)</a> likewise identified 12 unique mutations distributed throughout the WAS gene. Patients with classic WAS had 'more complex' mutations, resulting in termination codons, frameshifts, and early termination. By contrast, 4 unrelated patients with the X-linked thrombocytopenia phenotype had missense mutations affecting exon 2 (in 3) and a splice site mutation affecting exon 9 (in 1). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7579329+7579347" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#48" class="mim-tip-reference" title="Schindelhauer, D., Weiss, M., Hellebrand, H., Golla, A., Hergersberg, M., Seger, R., Belohradsky, B. H., Meindl, A. <strong>Wiskott-Aldrich syndrome: no strict genotype-phenotype correlations but clustering of missense mutations in the amino-terminal part of the WASP gene product.</strong> Hum. Genet. 98: 68-76, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8682510/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8682510</a>] [<a href="https://doi.org/10.1007/s004390050162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8682510">Schindelhauer et al. (1996)</a> found no genotype/phenotype correlation emerge after a comparison of the identified mutations with the resulting clinical picture for a classic WAS phenotype. A mild course, reminiscent of X-linked thrombocytopenia, or an attenuated phenotype was more often associated with missense than with the other types of mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8682510" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Greer, W. L., Shehabeldin, A., Schulman, J., Junker, A., Siminovitch, K. A. <strong>Identification of WASP mutations, mutation hotspots and genotype-phenotype disparities in 24 patients with the Wiskott-Aldrich syndrome.</strong> Hum. Genet. 98: 685-690, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8931701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8931701</a>] [<a href="https://doi.org/10.1007/s004390050285" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8931701">Greer et al. (1996)</a> examined the genotypes and phenotypes of 24 patients with WAS and compared them with other known mutations of the WASP gene. They demonstrated clustering of WASP mutations within the 4 most N-terminal exons of the gene and identified arg86 as the most prominent hotspot for WASP mutations. They noted the prominence of missense mutations among patients with milder forms of WAS, while noting that missense mutations also comprise a substantial portion of mutations in patients with severe forms of the disease. <a href="#20" class="mim-tip-reference" title="Greer, W. L., Shehabeldin, A., Schulman, J., Junker, A., Siminovitch, K. A. <strong>Identification of WASP mutations, mutation hotspots and genotype-phenotype disparities in 24 patients with the Wiskott-Aldrich syndrome.</strong> Hum. Genet. 98: 685-690, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8931701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8931701</a>] [<a href="https://doi.org/10.1007/s004390050285" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8931701">Greer et al. (1996)</a> concluded that phenotypes and genotypes of WAS are not well correlated; phenotypic outcome cannot be reliably predicted on the basis of WASP genotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8931701" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Lemahieu, V., Gastier, J. M., Francke, U. <strong>Novel mutations in the Wiskott-Aldrich syndrome protein gene and their effects on transcriptional, translational, and clinical phenotypes.</strong> Hum. Mutat. 14: 54-66, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10447259/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10447259</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)14:1<54::AID-HUMU7>3.0.CO;2-E" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10447259">Lemahieu et al. (1999)</a> identified 17 WASP gene mutations, 12 of which were novel. All missense mutations were located in exons 1 to 4. Most of the nonsense, frameshift, and splice site mutations were found in exons 6 to 11. Mutations that alter splice sites led to the synthesis of several types of mRNAs, a fraction of which represented the normally spliced product. The presence of normally spliced transcripts was correlated with a milder phenotype. When one such case was studied by Western blot analysis, reduced amounts of normal-sized WASP were present. In other cases as well, a correlation was found between the amount of normal or mutant WASP present and the phenotypes of the affected individuals. No protein was detected in 2 individuals with severe Wiskott-Aldrich syndrome. Reduced levels of a normal-sized WASP with a missense mutation were seen in 2 individuals with X-linked thrombocytopenia. <a href="#35" class="mim-tip-reference" title="Lemahieu, V., Gastier, J. M., Francke, U. <strong>Novel mutations in the Wiskott-Aldrich syndrome protein gene and their effects on transcriptional, translational, and clinical phenotypes.</strong> Hum. Mutat. 14: 54-66, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10447259/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10447259</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)14:1<54::AID-HUMU7>3.0.CO;2-E" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10447259">Lemahieu et al. (1999)</a> concluded that mutation analysis at the DNA level is not sufficient for predicting clinical course, and that studies at the transcript and protein levels are needed for a better assessment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10447259" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#25" class="mim-tip-reference" title="Imai, K., Morio, T., Zhu, Y., Jin, Y., Itoh, S., Kajiwara, M., Yata, J., Mizutani, S., Ochs, H. D., Nonoyama, S. <strong>Clinical course of patients with WASP gene mutations.</strong> Blood 103: 456-464, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12969986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12969986</a>] [<a href="https://doi.org/10.1182/blood-2003-05-1480" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12969986">Imai et al. (2004)</a> characterized WASP gene mutations in 50 Japanese patients and analyzed the clinical phenotype and course of each. All patients with missense mutations were WASP-positive, i.e., showed presence of the WASP protein; in contrast, patients with nonsense mutations, large deletions, small deletions, and small insertions were WASP-negative. Patients with splice anomalies were either WASP-positive or WASP-negative. The clinical phenotype of each patient correlated with the presence or absence of WASP. Lack of WASP expression was associated with susceptibility to bacterial, viral, fungal, and Pneumocystis carinii infections and with severe eczema, intestinal hemorrhage, death from intracranial bleeding, and malignancies. Rates for overall survival or survival without intracranial hemorrhage or other serious complications were significantly lower in WASP-negative patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12969986" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<div class="mim-changed mim-change"><p><a href="#56" class="mim-tip-reference" title="Vallee, T. C., Glasmacher, J. S., Buchner, H., Arkwright, P. D., Behrends, U., Bondarenko, A., Browning, M. J., Buchbinder, D., Cattoni, A., Chernyshova, L., Ciznar, P., Cole, T., and 43 others. <strong>Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival.</strong> Blood 143: 2504-2516, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38579284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38579284</a>] [<a href="https://doi.org/10.1182/blood.2023021411" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="38579284">Vallee et al. (2024)</a> evaluated 577 individuals with Wiskott-Aldrich syndrome from 63 centers in 26 countries born between 1932 and 2014. The median age at diagnosis was 1.5 years (range, 0-68). Of these patients, 464 (80.4%) were alive at last follow-up, and the median age at last follow-up was 8.9 years (range, 0.3-71.1). This resulted in a total of 6,118 reported patient-years. Overall survival of the cohort, censored at hematopoietic stem cell transplant or gene therapy, was 82% (95% confidence interval (CI) 78-87) at age 15 years and 70% (95% CI 61-80) at 30 years. <a href="#56" class="mim-tip-reference" title="Vallee, T. C., Glasmacher, J. S., Buchner, H., Arkwright, P. D., Behrends, U., Bondarenko, A., Browning, M. J., Buchbinder, D., Cattoni, A., Chernyshova, L., Ciznar, P., Cole, T., and 43 others. <strong>Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival.</strong> Blood 143: 2504-2516, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38579284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38579284</a>] [<a href="https://doi.org/10.1182/blood.2023021411" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="38579284">Vallee et al. (2024)</a> found that those with a missense variant in exon 1 or 2 or the intronic hotspot variant c.559+5G-A (<a href="#0016">300392.0016</a>) (called class I variants) had a better outcome than those with any other variant (class II variants). Individuals with class I variants had a 15-year odds of survival of 93% (95% CI 89-98) and a 30-year odds of survival of 91% (95% CI 86-97), compared with 71% (95% CI 62-81) and 48% (95% CI 34-68) in patients with class II variants. The cumulative incidence rates of disease-related complications such as severe bleeding (p = 0.007), life-threatening infection (p less than 0.0001), and autoimmunity (p = 0.004) occurred significantly later in patients with a class I variant. The cumulative incidence of malignancy (p = 0.6) was not different between classes I and II. <a href="#56" class="mim-tip-reference" title="Vallee, T. C., Glasmacher, J. S., Buchner, H., Arkwright, P. D., Behrends, U., Bondarenko, A., Browning, M. J., Buchbinder, D., Cattoni, A., Chernyshova, L., Ciznar, P., Cole, T., and 43 others. <strong>Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival.</strong> Blood 143: 2504-2516, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38579284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38579284</a>] [<a href="https://doi.org/10.1182/blood.2023021411" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="38579284">Vallee et al. (2024)</a> concluded that their study quantified the risk for specific disease-related complications and that the class of variant is a biomarker to predict the outcome in patients with WAS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38579284" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p></div>
|
|
</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="#12" class="mim-tip-reference" title="Derry, J. M. J., Kerns, J. A., Weinberg, K. I., Ochs, H. D., Volpini, V., Estivill, X., Walker, A. P., Francke, U. <strong>WASP gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia.</strong> Hum. Molec. Genet. 4: 1127-1135, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528199</a>] [<a href="https://doi.org/10.1093/hmg/4.7.1127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528199">Derry et al. (1995)</a> stated that Wasp may be a candidate for involvement in 'scurfy,' a T cell-mediated fatal lymphoreticular disease of mice that had previously been proposed as a mouse homolog of Wiskott-Aldrich syndrome (<a href="#38" class="mim-tip-reference" title="Lyon, M. F., Peters, J., Glenister, P. H., Ball, S., Wright, E. <strong>The scurfy mouse mutant has previously unrecognized hematological abnormalities and resembles Wiskott-Aldrich syndrome.</strong> Proc. Nat. Acad. Sci. 87: 2433-2437, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2320565/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2320565</a>] [<a href="https://doi.org/10.1073/pnas.87.7.2433" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2320565">Lyon et al., 1990</a>). Northern analysis of sf tissue samples indicated the presence of Wasp mRNA in liver and skin, presumably as a consequence of lymphocyte infiltration, but no abnormalities in the amount or size of mRNA were identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8528199+2320565" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#51" class="mim-tip-reference" title="Snapper, S. B., Rosen, F. S., Mizoguchi, E., Cohen, P., Khan, W., Liu, C. H., Hagemann, T. L., Kwan, S. P., Ferrini, R., Davidson, L., Bhan, A. K., Alt, F. W. <strong>Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation.</strong> Immunity 9: 81-91, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9697838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9697838</a>] [<a href="https://doi.org/10.1016/s1074-7613(00)80590-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9697838">Snapper et al. (1998)</a> found that Wasp -/- mice had normal lymphocyte development and Ig levels and responded well to T-dependent and -independent antigens. However, they had decreased peripheral blood lymphocyte and platelet numbers and developed chronic colitis. Responses to anti-Cd3e (<a href="/entry/186830">186830</a>) stimulation were impaired in Wasp -/- T cells, whereas Wasp -/- B cells responded normally to anti-Ig. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9697838" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Humblet-Baron, S., Sather, B., Anover, S., Becker-Herman, S., Kasprowicz, D. J., Khim, S., Nguyen, T., Hudkins-Loya, K., Alpers, C. E., Ziegler, S. F., Ochs, H., Torgerson, T., Campbell, D. J., Rawlings, D. J. <strong>Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis.</strong> J. Clin. Invest. 117: 407-418, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17218989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17218989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17218989[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/10.1172/JCI29539" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17218989">Humblet-Baron et al. (2007)</a> found that Wasp -/- mice developed early-onset, high-titer autoantibodies. Wasp -/- Tregs failed to compete effectively in vivo and were unable to maintain immunologic tolerance in Treg -/- mice. Flow cytometric analysis demonstrated reduced expression of adhesion molecules and chemokine receptors necessary for nonlymphoid tissue entry in Wasp -/- Tregs, suggesting a defect in peripheral Treg activation. <a href="#24" class="mim-tip-reference" title="Humblet-Baron, S., Sather, B., Anover, S., Becker-Herman, S., Kasprowicz, D. J., Khim, S., Nguyen, T., Hudkins-Loya, K., Alpers, C. E., Ziegler, S. F., Ochs, H., Torgerson, T., Campbell, D. J., Rawlings, D. J. <strong>Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis.</strong> J. Clin. Invest. 117: 407-418, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17218989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17218989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17218989[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/10.1172/JCI29539" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17218989">Humblet-Baron et al. (2007)</a> concluded that altered fitness of Tregs may explain the autoimmune features of WAS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17218989" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#40" class="mim-tip-reference" title="Marangoni, F., Trifari, S., Scaramuzza, S., Panaroni, C., Martino, S., Notarangelo, L. D., Baz, Z., Metin, A., Cattaneo, F., Villa, A., Aiuti, A., Battaglia, M., Roncarolo, M.-G., Dupre, L. <strong>WASP regulates suppressor activity of human and murine CD4+CD25+FOXP3+ natural regulatory T cells.</strong> J. Exp. Med. 204: 369-380, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17296785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17296785</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17296785[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/10.1084/jem.20061334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17296785">Marangoni et al. (2007)</a> found that Wasp -/- natural Tregs (nTregs) engrafted poorly in immunized mice and failed to proliferate or produce Tgfb (<a href="/entry/190180">190180</a>). Wasp -/- nTregs also showed reduced suppressor cell function against either wildtype or Wasp -/- effector T cells. Human nTregs from WAS patients showed a similar phenotype. <a href="#40" class="mim-tip-reference" title="Marangoni, F., Trifari, S., Scaramuzza, S., Panaroni, C., Martino, S., Notarangelo, L. D., Baz, Z., Metin, A., Cattaneo, F., Villa, A., Aiuti, A., Battaglia, M., Roncarolo, M.-G., Dupre, L. <strong>WASP regulates suppressor activity of human and murine CD4+CD25+FOXP3+ natural regulatory T cells.</strong> J. Exp. Med. 204: 369-380, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17296785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17296785</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17296785[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/10.1084/jem.20061334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17296785">Marangoni et al. (2007)</a> proposed that WASP plays an important role in the activation and suppressor functions of nTregs and that dysfunction or incorrect localization of nTregs may contribute to autoimmunity in WAS patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17296785" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Maillard, M. H., Cotta-de-Almeida, V., Takeshima, F., Nguyen, D. D., Michetti, P., Nagler, C., Bhan, A. K., Snapper, S. B. <strong>The Wiskott-Aldrich syndrome protein is required for the function of CD4+CD25+Foxp3+ regulatory T cells.</strong> J. Exp. Med. 204: 381-391, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17296786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17296786</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17296786[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/10.1084/jem.20061338" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17296786">Maillard et al. (2007)</a> demonstrated that Wasp -/- mice have decreased numbers of nTregs in thymus and peripheral organs. Wasp -/- nTregs failed to protect against development of colitis in vivo and failed to home to mesenteric mucosa and peripheral sites upon adoptive transfer into wildtype recipient mice. Wasp -/- nTregs had reduced suppressor function in vitro, which could be restored by preincubation with Il2 (<a href="/entry/147680">147680</a>) and antigen receptor activation, and they were defective in Il10 (<a href="/entry/124092">124092</a>) secretion. <a href="#39" class="mim-tip-reference" title="Maillard, M. H., Cotta-de-Almeida, V., Takeshima, F., Nguyen, D. D., Michetti, P., Nagler, C., Bhan, A. K., Snapper, S. B. <strong>The Wiskott-Aldrich syndrome protein is required for the function of CD4+CD25+Foxp3+ regulatory T cells.</strong> J. Exp. Med. 204: 381-391, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17296786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17296786</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17296786[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/10.1084/jem.20061338" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17296786">Maillard et al. (2007)</a> concluded that WASP is critical for nTreg function and that nTreg dysfunction is involved in autoimmunity associated with WASP deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17296786" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 2 different gene-targeting approaches, <a href="#9" class="mim-tip-reference" title="Cotta-de-Almeida, V., Westerberg, L., Maillard, M. H., Onaldi, D., Wachtel, H., Meelu, P., Chung, U., Xavier, R., Alt, F. W., Snapper, S. B. <strong>Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development.</strong> Proc. Nat. Acad. Sci. 104: 15424-15429, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17878299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17878299</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17878299[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.0706881104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17878299">Cotta-de-Almeida et al. (2007)</a> generated mouse T lymphocytes lacking both Wasp and N-Wasp. These double-knockout T cells were indistinguishable from wildtype T cells, but T-cell development was markedly altered in double-knockout mice. Flow cytometric analysis demonstrated reduced thymocyte and peripheral T-cell numbers in double-knockout mice. <a href="#9" class="mim-tip-reference" title="Cotta-de-Almeida, V., Westerberg, L., Maillard, M. H., Onaldi, D., Wachtel, H., Meelu, P., Chung, U., Xavier, R., Alt, F. W., Snapper, S. B. <strong>Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development.</strong> Proc. Nat. Acad. Sci. 104: 15424-15429, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17878299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17878299</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17878299[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.0706881104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17878299">Cotta-de-Almeida et al. (2007)</a> found that the combined activity of Wasp and N-Wasp was important for transition from Cd4/Cd8 double-negative thymocytes to Cd4/Cd8 double-positive thymocytes. In addition, double-knockout mice exhibited decreased migration of single-positive T cells from the thymus. <a href="#9" class="mim-tip-reference" title="Cotta-de-Almeida, V., Westerberg, L., Maillard, M. H., Onaldi, D., Wachtel, H., Meelu, P., Chung, U., Xavier, R., Alt, F. W., Snapper, S. B. <strong>Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development.</strong> Proc. Nat. Acad. Sci. 104: 15424-15429, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17878299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17878299</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17878299[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.0706881104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17878299">Cotta-de-Almeida et al. (2007)</a> concluded that WASP has a unique role in peripheral T-cell function, but T-cell development depends on the combined activity of WASP and N-WASP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17878299" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#65" class="mim-tip-reference" title="Westerberg, L. S., Meelu, P., Baptista, M., Eston, M. A., Adamovich, D. A., Cotta-de-Almeida, V., Seed, B., Rosen, M. K., Vandenberghe, P., Thrasher, A. J., Klein, C., Alt, F. W., Snapper, S. B. <strong>Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes.</strong> J. Exp. Med. 207: 1145-1152, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20513746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20513746</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20513746[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/10.1084/jem.20091245" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20513746">Westerberg et al. (2010)</a> created mice with mutations in the mouse Wasp gene corresponding to the human leu270-to-pro (L270P; <a href="#0012">300392.0012</a>) and ile294-to-thr (I294T; <a href="#0025">300392.0025</a>) mutations, which cause X-linked neutropenia (SCNX; <a href="/entry/300299">300299</a>). These mutations interfered with normal lymphocyte activation by inducing a marked increase in polymerized actin, decreased cell spreading, and increased apoptosis associated with increased genomic instability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20513746" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>25 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/300392" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=300392[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 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, 1-BP DEL, 211T
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2147262829 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2147262829;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=rs2147262829" 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=rs2147262829" 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=RCV000011862" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011862" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011862</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Wiskott-Aldrich syndrome (WAS; <a href="/entry/301000">301000</a>) who on Northern blot analysis lacked a visible transcript for WAS, <a href="#13" class="mim-tip-reference" title="Derry, J. M. J., Ochs, H. D., Francke, U. <strong>Isolation of a novel gene mutated in Wiskott-Aldrich syndrome.</strong> Cell 78: 635-644, 1994. Note: Erratum: Cell 79: following 922, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069912</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90528-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069912">Derry et al. (1994)</a> found deletion of a thymine at nucleotide position 211. The change interrupted the predicted open reading frame and led to a termination signal 16 codons downstream. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8069912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, ARG86LEU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs132630268 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs132630268;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=rs132630268" 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=rs132630268" 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=RCV000011863" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011863" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011863</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Wiskott-Aldrich syndrome (WAS; <a href="/entry/301000">301000</a>), <a href="#13" class="mim-tip-reference" title="Derry, J. M. J., Ochs, H. D., Francke, U. <strong>Isolation of a novel gene mutated in Wiskott-Aldrich syndrome.</strong> Cell 78: 635-644, 1994. Note: Erratum: Cell 79: following 922, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069912</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90528-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069912">Derry et al. (1994)</a> found a G-to-T transversion that changed codon 86 from an arginine to a leucine. The mutation was identified in the mother and maternal grandmother. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8069912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, ARG86HIS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs132630268 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs132630268;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=rs132630268" 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=rs132630268" 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=RCV000011864 OR RCV000414284 OR RCV000633305" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011864, RCV000414284, RCV000633305" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011864...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Wiskott-Aldrich syndrome (WAS; <a href="/entry/301000">301000</a>), unrelated to the patient with the arg86-to-leu mutation (<a href="#0002">300392.0002</a>), <a href="#13" class="mim-tip-reference" title="Derry, J. M. J., Ochs, H. D., Francke, U. <strong>Isolation of a novel gene mutated in Wiskott-Aldrich syndrome.</strong> Cell 78: 635-644, 1994. Note: Erratum: Cell 79: following 922, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069912</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90528-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8069912">Derry et al. (1994)</a> identified a G-to-A transition at nucleotide 291 changing the same arginine to a histidine. The patient's mother and maternal grandmother were heterozygous for the mutant allele. In one instance, the normal codon CGC was changed to CTC (leu); in the other instance, it was changed to CAC (his). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8069912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#48" class="mim-tip-reference" title="Schindelhauer, D., Weiss, M., Hellebrand, H., Golla, A., Hergersberg, M., Seger, R., Belohradsky, B. H., Meindl, A. <strong>Wiskott-Aldrich syndrome: no strict genotype-phenotype correlations but clustering of missense mutations in the amino-terminal part of the WASP gene product.</strong> Hum. Genet. 98: 68-76, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8682510/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8682510</a>] [<a href="https://doi.org/10.1007/s004390050162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8682510">Schindelhauer et al. (1996)</a> found extremely variable expression of a disease in a large Swiss family with the R86H mutation of 5 affected males. One died in infancy from infections and 2 were diagnosed as having the classic WAS phenotype. In contrast, 2 brothers had a mild phenotype with survival into adulthood and had children of their own. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8682510" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 THROMBOCYTOPENIA, X-LINKED, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, ALA56VAL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs132630269 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs132630269;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=rs132630269" 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=rs132630269" 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=RCV000011865 OR RCV001563489 OR RCV002243636 OR RCV003764557" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011865, RCV001563489, RCV002243636, RCV003764557" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011865...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old boy with thrombocytopenia with small-sized platelets (THC1; <a href="/entry/313900">313900</a>) diagnosed at 3 months of age, <a href="#57" class="mim-tip-reference" title="Villa, A., Notarangelo, L., Macchi, P., Mantuano, E., Cavagni, G., Brugnoni, D., Strina, D., Patrosso, M. C., Ramenghi, U., Sacco, M. G., Ugazio, A., Vezzoni, P. <strong>X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene.</strong> Nature Genet. 9: 414-417, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7795648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7795648</a>] [<a href="https://doi.org/10.1038/ng0495-414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7795648">Villa et al. (1995)</a> found a C-to-T transition in exon 2 at nucleotide 201, which was predicted to cause substitution of valine for alanine at codon 56. The patient had never shown eczema or increased susceptibility to infection. The same mutation was found in 1 allele in the mother. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7795648" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 THROMBOCYTOPENIA, X-LINKED, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, ALA236GLU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs132630270 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs132630270;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=rs132630270" 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=rs132630270" 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=RCV000011866" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011866" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011866</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old boy with a negative family history and thrombocytopenia with small-sized platelets (THC1; <a href="/entry/313900">313900</a>) who presented with petechiae at the age of 5 months, <a href="#57" class="mim-tip-reference" title="Villa, A., Notarangelo, L., Macchi, P., Mantuano, E., Cavagni, G., Brugnoni, D., Strina, D., Patrosso, M. C., Ramenghi, U., Sacco, M. G., Ugazio, A., Vezzoni, P. <strong>X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene.</strong> Nature Genet. 9: 414-417, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7795648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7795648</a>] [<a href="https://doi.org/10.1038/ng0495-414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7795648">Villa et al. (1995)</a> found a C-to-G transversion at nucleotide 741 in exon 7, predicted to lead to substitution of glutamic acid for alanine at codon 236. The mother showed the same mutation in 1 allele. The patient had had mild and transient eczema at 10 months of age but had never shown susceptibility to infections. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7795648" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 THROMBOCYTOPENIA, X-LINKED, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, 1-BP INS, 512C
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011867" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011867" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011867</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 9-year-old boy who presented with petechiae at the age of 6 months and was found to have thrombocytopenia with small-sized platelets (THC1; <a href="/entry/313900">313900</a>), <a href="#57" class="mim-tip-reference" title="Villa, A., Notarangelo, L., Macchi, P., Mantuano, E., Cavagni, G., Brugnoni, D., Strina, D., Patrosso, M. C., Ramenghi, U., Sacco, M. G., Ugazio, A., Vezzoni, P. <strong>X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene.</strong> Nature Genet. 9: 414-417, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7795648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7795648</a>] [<a href="https://doi.org/10.1038/ng0495-414" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7795648">Villa et al. (1995)</a> found a C insertion in a stretch of 5 cytosines between nucleotides 512 and 516 (in exon 1). The insertion caused a shift in the reading frame after codon 160, leading to a premature termination 8 codons downstream at nucleotides 535-537. The same mutation was detected in 1 allele in the mother. The patient had never developed eczema and showed no unusual susceptibility to infections. A younger brother was also affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7795648" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, ARG34TER
|
|
</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> rs132630271 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs132630271;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/rs132630271?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=rs132630271" 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=rs132630271" 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=RCV000011868 OR RCV003764558" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011868, RCV003764558" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011868...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>One of 11 new mutations identified by <a href="#32" class="mim-tip-reference" title="Kwan, S.-P., Hagemann, T. L., Radtke, B. E., Blaese, R. M., Rosen, F. S. <strong>Identification of mutations in the Wiskott-Aldrich syndrome gene and characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent to the disease gene.</strong> Proc. Nat. Acad. Sci. 92: 4706-4710, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7753869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7753869</a>] [<a href="https://doi.org/10.1073/pnas.92.10.4706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7753869">Kwan et al. (1995)</a> in patients with Wiskott-Aldrich syndrome (WAS; <a href="/entry/301000">301000</a>) was a CGA-to-TGA transition in exon 1, resulting in an arg34-to-ter conversion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7753869" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, 6-BP INS, NT434
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776743 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776743;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=rs587776743" 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=rs587776743" 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=RCV000011870" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011870" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011870</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>One of 11 mutations in patients with Wiskott-Aldrich syndrome (WAS; <a href="/entry/301000">301000</a>) identified by <a href="#32" class="mim-tip-reference" title="Kwan, S.-P., Hagemann, T. L., Radtke, B. E., Blaese, R. M., Rosen, F. S. <strong>Identification of mutations in the Wiskott-Aldrich syndrome gene and characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent to the disease gene.</strong> Proc. Nat. Acad. Sci. 92: 4706-4710, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7753869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7753869</a>] [<a href="https://doi.org/10.1073/pnas.92.10.4706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7753869">Kwan et al. (1995)</a> was a 6-bp insertion (ACGAGG) at nucleotide 434 resulting in the introduction of 2 additional amino acids, asp and glu. The mutation occurred in exon 4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7753869" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#61" class="mim-tip-reference" title="Wada, T., Schurman, S. H., Otsu, M., Garabedian, E. K., Ochs, H. D., Nelson, D. L., Candotti, F. <strong>Somatic mosaicism in Wiskott-Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism.</strong> Proc. Nat. Acad. Sci. 98: 8697-8702, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11447283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11447283</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11447283[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.151260498" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11447283">Wada et al. (2001)</a> described a case of somatic mosaicism for this mutation caused by in vivo reversion. The patient came from a kindred in which 6 males in 4 sibships connected by carrier females had Wiskott-Aldrich syndrome (<a href="/entry/301000">301000</a>). At the age of 10 months, the proband had encephalitis, and between the ages of 2 and 5 years, he had recurrent bruising, eczema, and recurrent otitis media. At age 5, his platelet count was found to be low. Elective splenectomy corrected the platelet number and size. Shortly after splenectomy, he suffered from pneumococcal meningitis. Frequent upper respiratory and/or ear infections and continued eczema occurred until the age of 12 years when the patient was hospitalized for vasculitic rash, thrombocytopenia, and an illness resembling rheumatoid arthritis with concurrent dysgammaglobulinemia and nephritis. The same year, he developed pneumococcal meningitis and sepsis, which were successfully treated. One month later, another episode of pneumococcal meningitis occurred. At age 16, he developed right mastoiditis. From his 20s to the time of report at age 43, the patient had been relatively well, with complaints of sinusitis responding to antibiotic treatment. A maternal uncle developed petechiae early after birth and died at 6 months of age. His brother had a severe WAS phenotype, including thrombocytopenia, infections, arthritis, and vasculitis, and died of renal failure at the age of 33 years. Two maternal cousins also had severe WAS symptoms; one died from pulmonary hemorrhage at age 2.5 years and the other from lymphoma at age 18 years. <a href="#61" class="mim-tip-reference" title="Wada, T., Schurman, S. H., Otsu, M., Garabedian, E. K., Ochs, H. D., Nelson, D. L., Candotti, F. <strong>Somatic mosaicism in Wiskott-Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism.</strong> Proc. Nat. Acad. Sci. 98: 8697-8702, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11447283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11447283</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11447283[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.151260498" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11447283">Wada et al. (2001)</a> identified the ACGAGG insertion in the WAS gene of the proband. They documented somatic mosaicism in the patient, most of whose T lymphocytes expressed nearly normal levels of WAS protein and were found to lack the deleterious mutation. The sequence surrounding the mutation site showed that the 6-bp insertion followed a tandem repeat of the same 6 nucleotides. These findings strongly suggested that DNA polymerase slippage was the cause of the original germline insertion mutation in this family and that the same mechanism was responsible for its deletion in one of the T-cell progenitors in the proband, thus leading to reversion mosaicism and clinical cure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11447283" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WISKOTT-ALDRICH SYNDROME, ATTENUATED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, SER82PRO
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs132630272 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs132630272;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=rs132630272" 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=rs132630272" 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=RCV000011871 OR RCV001509116" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011871, RCV001509116" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011871...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In addition to classic Wiskott-Aldrich syndrome on the one hand and isolated thrombocytopenia on the other, some patients with mutations in the WAS gene have atypical or attenuated WAS (<a href="/entry/301000">301000</a>). In contrast to classic WAS patients, the boys manifested only a mild to moderately severe hemorrhagic diathesis during childhood, had mild or no eczema, and lacked a history of severe recurrent infections. As in classic WAS patients, the boys with attenuated WAS showed variable expression of immune abnormalities and their T cells showed lack of proliferative responses to the periodate mitogen, a finding apparently restricted to, and diagnostic of, WAS (<a href="#50" class="mim-tip-reference" title="Siminovitch, K. A., Greer, W. L., Novogrodsky, A., Axelsson, B., Somani, A.-K., Peacocke, M. <strong>A diagnostic assay for the Wiskott-Aldrich syndrome and its variant forms.</strong> J. Investig. Med. 43: 159-169, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7735919/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7735919</a>]" pmid="7735919">Siminovitch et al., 1995</a>). One of the attenuated or atypical cases of WAS reported by <a href="#29" class="mim-tip-reference" title="Kolluri, R., Shehabeldin, A., Peacocke, M., Lamhonwah, A.-M., Teichert-Kuliszewska, K., Weissman, S. M., Siminovitch, K. A. <strong>Identification of WASP mutations in patients with Wiskott-Aldrich syndrome and isolated thrombocytopenia reveals allelic heterogeneity at the WAS locus.</strong> Hum. Molec. Genet. 4: 1119-1126, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528198</a>] [<a href="https://doi.org/10.1093/hmg/4.7.1119" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8528198">Kolluri et al. (1995)</a> was a 27-year-old man who had easy bruising, epistaxis since infancy, mild eczema, and recurrent pneumonia. Renal failure from the age of 13 years required dialysis. A splenectomy was performed at age 23 years following intracranial hemorrhage. The patient was found to carry a T-to-C transition of nucleotide 278, resulting in a ser82-to-pro substitution in exon 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7735919+8528198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0010" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 THROMBOCYTOPENIA, X-LINKED, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, THR45MET
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs132630273 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs132630273;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=rs132630273" 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=rs132630273" 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=RCV000011872 OR RCV000851684 OR RCV001037597 OR RCV001172206 OR RCV004748516 OR RCV004760326" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011872, RCV000851684, RCV001037597, RCV001172206, RCV004748516, RCV004760326" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011872...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#11" class="mim-tip-reference" title="de Saint Basile, G., Lagelouse, R. D., Lambert, N., Schwarz, K., Le Mareck, B., Odent, S., Schlegel, N., Fischer, A. <strong>Isolated X-linked thrombocytopenia in two unrelated families is associated with point mutations in the Wiskott-Aldrich syndrome protein gene.</strong> J. Pediat. 129: 56-62, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8757563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8757563</a>] [<a href="https://doi.org/10.1016/s0022-3476(96)70190-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8757563">De Saint Basile et al. (1996)</a> described a new mutation in a patient from a family with X-linked thrombocytopenia (THC1; <a href="/entry/313900">313900</a>). Exon 2 products showed abnormal migration by single-strand conformational polymorphism analysis. A 168C-T transition produced a thr45-to-met missense mutation with no change in charge. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8757563" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#23" class="mim-tip-reference" title="Ho, L. L., Ayling, J., Prosser, I., Kronenberg, H., Iland, H., Joshua, D. <strong>Missense C168T in the Wiskott-Aldrich syndrome protein gene is a common mutation in X-linked thrombocytopenia.</strong> Brit. J. Haemat. 112: 76-80, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11167787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11167787</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2001.02465.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11167787">Ho et al. (2001)</a> found the thr45-to-met mutation in affected members of a large Syrian-Lebanese family with X-linked thrombocytopenia. Five family members had undergone splenectomy with rapid and sustained normalization of their platelet numbers. <a href="#23" class="mim-tip-reference" title="Ho, L. L., Ayling, J., Prosser, I., Kronenberg, H., Iland, H., Joshua, D. <strong>Missense C168T in the Wiskott-Aldrich syndrome protein gene is a common mutation in X-linked thrombocytopenia.</strong> Brit. J. Haemat. 112: 76-80, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11167787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11167787</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2001.02465.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11167787">Ho et al. (2001)</a> pointed out that exon 2 is the most common site for mutations associated with XLT and mild forms of WAS, and the 168C-T transition is the most frequent. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11167787" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, 1-BP DEL, 1127G
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776744 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776744;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=rs587776744" 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=rs587776744" 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=RCV000011873" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011873" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011873</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Wiskott-Aldrich syndrome (WAS; <a href="/entry/301000">301000</a>), <a href="#4" class="mim-tip-reference" title="Ariga, T., Yamada, M., Sakiyama, Y., Tatsuzawa, O. <strong>A case of Wiskott-Aldrich syndrome with dual mutations in exon 10 of the WASP gene: an additional de novo one-base insertion, which restores frame shift due to an inherent one-base deletion, detected in the major population of the patient's peripheral blood lymphocytes. (Letter)</strong> Blood 92: 699-701, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9657775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9657775</a>]" pmid="9657775">Ariga et al. (1998)</a> observed 2 mutations in exon 10 of the WASP gene. One mutation was a 1-bp insertion (A) at nucleotide 1099 or 1100. The other was a 1-base deletion (G) from 5 consecutive Gs at nucleotides 1127 to 1131. On further study it was found that some clones contained only the insertion mutation and the patient's mother and sister, who were both carriers, had only the deletion mutation. It was suggested that the insertion mutation occurred somatically in a hematologic progenitor and was potentially capable of correcting the inherited defect. The proband died at the age of 4 years from intracranial hemorrhage; 2 older brothers who also had Wiskott-Aldrich syndrome died at the ages of 10 months and 47 months. It was uncertain whether the proband's disorder was milder as a result of the second mutation. Spontaneous in vivo reversion to normal of an inherited mutation was reported in a patient with adenosine deaminase deficiency (<a href="/entry/102700#0026">102700.0026</a>) by <a href="#22" class="mim-tip-reference" title="Hirschhorn, R., Yang, D. R., Puck, J. M., Huie, M. L., Jiang, C.-K., Kurlandsky, L. E. <strong>Spontaneous in vivo reversion to normal of an inherited mutation in a patient with adenosine deaminase deficiency.</strong> Nature Genet. 13: 290-295, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673127</a>] [<a href="https://doi.org/10.1038/ng0796-290" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8673127">Hirschhorn et al. (1996)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9657775+8673127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 NEUTROPENIA, SEVERE CONGENITAL, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, LEU270PRO
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs132630274 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs132630274;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=rs132630274" 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=rs132630274" 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=RCV000011874 OR RCV001291553 OR RCV001851800" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011874, RCV001291553, RCV001851800" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011874...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family in which males showed severe congenital neutropenia in an X-linked recessive pedigree pattern (SCNX; <a href="/entry/300299">300299</a>) with affected males in 3 sibships in 3 generations, <a href="#15" class="mim-tip-reference" title="Devriendt, K., Kim, A. S., Mathijs, G., Frints, S. G. M., Schwartz, M., Van den Oord, J. J., Verhoef, G. E. G., Boogaerts, M. A., Fryns, J.-P., You, D., Rosen, M. K., Vandenberghe, P. <strong>Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia.</strong> Nature Genet. 27: 313-317, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11242115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11242115</a>] [<a href="https://doi.org/10.1038/85886" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11242115">Devriendt et al. (2001)</a> demonstrated a constitutively activating mutation in WASP: an 843T-C transition causing a leu270-to-pro (L270P) mutation in the WAS gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11242115" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 THROMBOCYTOPENIA, X-LINKED, INTERMITTENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, PRO58ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs132630275 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs132630275;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=rs132630275" 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=rs132630275" 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=RCV000011875" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011875" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011875</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#42" class="mim-tip-reference" title="Notarangelo, L. D., Mazza, C., Giliani, S., D'Aria, C., Gandellini, F., Ravelli, C., Locatelli, M. G., Nelson, D. L., Ochs, H. D., Notarangelo, L. D. <strong>Missense mutations of the WASP gene cause intermittent X-linked thrombocytopenia.</strong> Blood 99: 2268-2269, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11877312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11877312</a>] [<a href="https://doi.org/10.1182/blood.v99.6.2268" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11877312">Notarangelo et al. (2002)</a> described 2 families in which affected males had a history of intermittent thrombocytopenia (THC1; <a href="/entry/313900">313900</a>) with consistently reduced platelet volume, in the absence of other major clinical features, and carried missense mutations of the WASP gene that allowed substantial protein expression. This observation broadened the spectrum of clinical phenotypes associated with WASP gene defects, and indicated the need for molecular analysis in males with reduced platelet volume, regardless of the platelet number. In 1 family reported by <a href="#42" class="mim-tip-reference" title="Notarangelo, L. D., Mazza, C., Giliani, S., D'Aria, C., Gandellini, F., Ravelli, C., Locatelli, M. G., Nelson, D. L., Ochs, H. D., Notarangelo, L. D. <strong>Missense mutations of the WASP gene cause intermittent X-linked thrombocytopenia.</strong> Blood 99: 2268-2269, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11877312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11877312</a>] [<a href="https://doi.org/10.1182/blood.v99.6.2268" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11877312">Notarangelo et al. (2002)</a>, the index case was that of a 7-year-old boy in whom petechiae developed at 1 month of age. He had mild and transient antecubital eczema in infancy. A diagnosis of idiopathic thrombocytopenia was made at the age of 2 years. He continued to have intermittent petechiae and occasional epistaxis associated with variability in the platelet count, but he had consistently low mean platelet volume. His 4-year-old brother and a 39-year-old maternal uncle also had histories of intermittent petechiae, without other symptoms. In this family a 207C-G nucleotide substitution was found in exon 2 of the WAS gene in all 3 affected males, resulting in a pro58-to-arg (P58R) amino acid change. Heterozygosity for this mutation was detected in the mother of the 2 boys. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11877312" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 THROMBOCYTOPENIA, X-LINKED, INTERMITTENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, ILE481ASN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs132630276 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs132630276;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=rs132630276" 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=rs132630276" 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=RCV000011876" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011876" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011876</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a second family with intermittent thrombocytopenia (WAS; <a href="/entry/313900">313900</a>) reported by <a href="#42" class="mim-tip-reference" title="Notarangelo, L. D., Mazza, C., Giliani, S., D'Aria, C., Gandellini, F., Ravelli, C., Locatelli, M. G., Nelson, D. L., Ochs, H. D., Notarangelo, L. D. <strong>Missense mutations of the WASP gene cause intermittent X-linked thrombocytopenia.</strong> Blood 99: 2268-2269, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11877312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11877312</a>] [<a href="https://doi.org/10.1182/blood.v99.6.2268" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11877312">Notarangelo et al. (2002)</a>, a single male was affected, a 7-year-old boy who at the age of 3 years had petechiae and bruises. Clinical history was unremarkable for eczema and infection, and immunoglobulins were normal. Mutation analysis revealed a 1476T-A point mutation in exon 11 of the WAS gene, resulting in an ile481-to-asn (I481N) amino acid substitution. The mother was found to be a carrier of this mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11877312" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0015" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, 15,800-BP DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011877" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011877" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011877</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#36" class="mim-tip-reference" title="Lutskiy, M. I., Jones, L. N., Rosen, F. S., Remold-O'Donnell, E. <strong>An Alu-mediated deletion at Xp11.23 leading to Wiskott-Aldrich syndrome.</strong> Hum. Genet. 110: 515-519, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12073025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12073025</a>] [<a href="https://doi.org/10.1007/s00439-002-0716-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12073025">Lutskiy et al. (2002)</a> described a patient with Wiskott-Aldrich syndrome (WAS; <a href="/entry/301000">301000</a>) with a large deletion in the Xp11.23 region. The deletion, which totaled 15.8 kb, began downstream of DXS1696 and encompassed 13 kb upstream of WASP and included the distal and proximal promoters and exons 1 through 6. The upstream breakpoint was localized in an Alu element. A 26-bp recombinogenic element was located downstream of the 5-prime breakpoint. A 16-bp sequence just upstream of the 5-prime breakpoint shared close homology with the sequence that spanned the 3-prime breakpoint in intron 6. A heptanucleotide of unknown origin, CAGGGGG, linked the 5-prime and 3-prime breakpoints. <a href="#36" class="mim-tip-reference" title="Lutskiy, M. I., Jones, L. N., Rosen, F. S., Remold-O'Donnell, E. <strong>An Alu-mediated deletion at Xp11.23 leading to Wiskott-Aldrich syndrome.</strong> Hum. Genet. 110: 515-519, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12073025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12073025</a>] [<a href="https://doi.org/10.1007/s00439-002-0716-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12073025">Lutskiy et al. (2002)</a> stated that this was the largest deletion identified in a Wiskott-Aldrich syndrome patient. The diagnosis had been made at the age of 3 months when he presented with thrombocytopenia, small platelets, severe eczema, bloody diarrhea, and recurrent otitis media. He received regular immunoglobulin transfusions; at age 2 years, splenectomy was performed and, at age 4, he received a bone marrow transplant from an HLA-matched unrelated donor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12073025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
THROMBOCYTOPENIA, X-LINKED, 1, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, IVS6DS, G-A, +5
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs886039451 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886039451;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=rs886039451" 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=rs886039451" 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=RCV000413138 OR RCV001390443 OR RCV001810445 OR RCV001810446" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000413138, RCV001390443, RCV001810445, RCV001810446" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000413138...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Wiskott-Aldrich Syndrome</em></strong>
|
|
</p>
|
|
|
|
<p>In a patient with Wiskott-Aldrich syndrome (<a href="/entry/301000">301000</a>), <a href="#32" class="mim-tip-reference" title="Kwan, S.-P., Hagemann, T. L., Radtke, B. E., Blaese, R. M., Rosen, F. S. <strong>Identification of mutations in the Wiskott-Aldrich syndrome gene and characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent to the disease gene.</strong> Proc. Nat. Acad. Sci. 92: 4706-4710, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7753869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7753869</a>] [<a href="https://doi.org/10.1073/pnas.92.10.4706" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7753869">Kwan et al. (1995)</a> identified a G-to-A transition at position +5 of intron 6 of the WAS gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7753869" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<div class="mim-changed mim-change"><p>Using RT-PCR, <a href="#67" class="mim-tip-reference" title="Zhu, Q., Watanabe, C., Liu, T., Hollenbaugh, D., Blaese, R. M., Kanner, S. B., Aruffo, A., Ochs, H. D. <strong>Wiskott-Aldrich syndrome/X-linked thrombocytopenia: WASP gene mutations, protein expression, and phenotype.</strong> Blood 90: 2680-2689, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326235</a>]" pmid="9326235">Zhu et al. (1997)</a> found that the IVS6+5G-A variant resulted in 30% wildtype transcripts, and protein was present on Western blot at 3.5% of wildtype levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326235" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p></div>
|
|
|
|
<div class="mim-changed mim-change"><p><a href="#27" class="mim-tip-reference" title="Jin, Y., Mazza, C., Christie, J. R., Giliani, S., Fiorini, M., Mella, P., Gandellini, F., Stewart, D. M., Zhu, Q., Nelson, D. L., Notarangelo, L. D., Ochs, H. D. <strong>Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation.</strong> Blood 104: 4010-4019, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15284122/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15284122</a>] [<a href="https://doi.org/10.1182/blood-2003-05-1592" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15284122">Jin et al. (2004)</a> identified this variant as a mutational hotspot, present in in 6/227 (2.6%) of the WAS families they studied. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15284122" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p></div>
|
|
|
|
<div class="mim-changed mim-change"><p><a href="#56" class="mim-tip-reference" title="Vallee, T. C., Glasmacher, J. S., Buchner, H., Arkwright, P. D., Behrends, U., Bondarenko, A., Browning, M. J., Buchbinder, D., Cattoni, A., Chernyshova, L., Ciznar, P., Cole, T., and 43 others. <strong>Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival.</strong> Blood 143: 2504-2516, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38579284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38579284</a>] [<a href="https://doi.org/10.1182/blood.2023021411" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="38579284">Vallee et al. (2024)</a> catagorized the c.559+5G-A mutation as a class I variant, correlated with a milder phenotype and better outcome. It was present in 22/525 (4.2%) of WAS patients with definitive genetic information. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38579284" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p></div>
|
|
|
|
<p />
|
|
<p><strong><em>Thrombocytopenia 1</em></strong>
|
|
</p>
|
|
|
|
<p><a href="#26" class="mim-tip-reference" title="Inoue, H., Kurosawa, H., Nonoyama, S., Imai, K., Kumazaki, H., Matsunaga, T., Sato, Y., Sugita, K., Eguchi, M. <strong>X-linked thrombocytopenia in a girl.</strong> Brit. J. Haemat. 118: 1163-1165, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12199801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12199801</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2002.03740.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12199801">Inoue et al. (2002)</a> reported what they believed to be the first confirmed instance of X-linked thrombocytopenia (THC1; <a href="/entry/313900">313900</a>) in a female. She had the IVS6+5G-A mutation in the WAS gene. Her lymphocytes showed a random pattern of X-chromosome inactivation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12199801" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, IVS6AS, G-A, -1
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1602178087 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1602178087;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=rs1602178087" 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=rs1602178087" 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=RCV000011880" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011880" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011880</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#31" class="mim-tip-reference" title="Kwan, S. P., Hagemann, T. L., Blaese, R. M., Knutsen, A., Rosen, F. S. <strong>Scanning of the Wiskott-Aldrich syndrome (WAS) gene: identification of 18 novel alterations including a possible mutation hotspot at Arg86 resulting in thrombocytopenia, a mild WAS phenotype.</strong> Hum. Molec. Genet. 4: 1995-1998, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8595430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8595430</a>] [<a href="https://doi.org/10.1093/hmg/4.10.1995" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8595430">Kwan et al. (1995)</a> described a G-to-A transition at position -1 of intron 6 of the WAS gene in a patient with Wiskott-Aldrich syndrome (WAS; <a href="/entry/301000">301000</a>). <a href="#37" class="mim-tip-reference" title="Lutskiy, M. I., Sasahara, Y., Kenney, D. M., Rosen, F. S., Remold-O'Donnell, E. <strong>Wiskott-Aldrich syndrome in a female.</strong> Blood 100: 2763-2768, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12351383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12351383</a>] [<a href="https://doi.org/10.1182/blood-2002-02-0388" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12351383">Lutskiy et al. (2002)</a> studied a 14-month-old girl, a cousin of that patient, who had Wiskott-Aldrich syndrome presenting with thrombocytopenia, small platelets, and immunologic dysfunction. Sequencing of the WAS gene showed that the patient was heterozygous for the splice site mutation previously found in her maternal cousin. Levels of WASP in blood mononuclear cells were 60% of normal. X chromosome inactivation in the patient's blood cells was random, demonstrating that both maternal and paternal active X chromosomes were present. These findings indicated that this patient had a defect in the mechanisms that, in disease-free WAS carriers, lead to preferential survival/proliferation of cells bearing the active wildtype X chromosome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8595430+12351383" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, IVS6DS, T-G, +2
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1602177733 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1602177733;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=rs1602177733" 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=rs1602177733" 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=RCV000011881" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011881" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011881</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#3" class="mim-tip-reference" title="Andreu, N., Carreras, C., Prieto, F., Estivill, X., Volpini, V., Fillat, C. <strong>Identification and characterization of a novel splice-site mutation in a patient with Wiskott-Aldrich syndrome.</strong> J. Hum. Genet. 48: 590-593, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14566484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14566484</a>] [<a href="https://doi.org/10.1007/s10038-003-0083-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14566484">Andreu et al. (2003)</a> reported an IVS6+2T-G splice site mutation in the WAS gene in a boy with Wiskott-Aldrich syndrome (WAS; <a href="/entry/301000">301000</a>). As a consequence of the disruption of the normal splicing process, an abnormally long transcript of 38 nucleotides was generated. Such missplicing was probably due to the activation of a cryptic splice donor site located 38 nucleotides downstream of exon 6. The translation of such aberrant mRNA was predicted to produce a truncated protein with a premature stop at codon 190. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14566484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, 1-BP DEL, 11G
|
|
</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> rs587776745 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776745;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/rs587776745?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=rs587776745" 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=rs587776745" 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=RCV000011882 OR RCV001225126" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011882, RCV001225126" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011882...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#17" class="mim-tip-reference" title="Du, W., Kumaki, S., Uchiyama, T., Yachie, A., Looi, C. Y., Kawai, S., Minegishi, M., Ramesh, N., Geha, R. S., Sasahara, Y., Tsuchiya, S. <strong>A second-site mutation in the initiation codon of WAS (WASP) results in expansion of subsets of lymphocytes in an Wiskott-Aldrich syndrome patient.</strong> Hum. Mutat. 27: 370-375, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16511828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16511828</a>] [<a href="https://doi.org/10.1002/humu.20308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16511828">Du et al. (2006)</a> described somatic mosaicism in a 15-year-old Wiskott-Aldrich syndrome (WAS; <a href="/entry/301000">301000</a>) patient due to a second-hit mutation in the initiation codon of the WAS gene. The germline mutation was a single-basepair deletion in the WAS cDNA, 11delG, which resulted in a frameshift and abrogated protein expression (Gly4fsTer40). The patient had originally been described by <a href="#46" class="mim-tip-reference" title="Sasahara, Y., Kawai, S., Kumaki, S., Ohashi, Y., Minegishi, M., Tsuchiya, S. <strong>Novel mutations, no detectable mRNA and familial genetic analysis of the Wiskott-Aldrich syndrome protein gene in six Japanese patients with Wiskott-Aldrich syndrome.</strong> Europ. J. Pediat. 159: 23-30, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10653325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10653325</a>] [<a href="https://doi.org/10.1007/s004310050005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10653325">Sasahara et al. (2000)</a>. Seven years after chemotherapy for Hodgkin disease, expression of WASP was detected in a fraction of T and NK cells. These WASP-expressing cells had a 1A-T (M1_P5del) mutation in the initiation codon. <a href="#17" class="mim-tip-reference" title="Du, W., Kumaki, S., Uchiyama, T., Yachie, A., Looi, C. Y., Kawai, S., Minegishi, M., Ramesh, N., Geha, R. S., Sasahara, Y., Tsuchiya, S. <strong>A second-site mutation in the initiation codon of WAS (WASP) results in expansion of subsets of lymphocytes in an Wiskott-Aldrich syndrome patient.</strong> Hum. Mutat. 27: 370-375, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16511828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16511828</a>] [<a href="https://doi.org/10.1002/humu.20308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16511828">Du et al. (2006)</a> hypothesized that the second-site mutation in the initiation codon resulted in alternative translation initiation from the second ATG that is located downstream of the germline single-nucleotide deletion. The patient was in complete remission at the time of the report of <a href="#17" class="mim-tip-reference" title="Du, W., Kumaki, S., Uchiyama, T., Yachie, A., Looi, C. Y., Kawai, S., Minegishi, M., Ramesh, N., Geha, R. S., Sasahara, Y., Tsuchiya, S. <strong>A second-site mutation in the initiation codon of WAS (WASP) results in expansion of subsets of lymphocytes in an Wiskott-Aldrich syndrome patient.</strong> Hum. Mutat. 27: 370-375, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16511828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16511828</a>] [<a href="https://doi.org/10.1002/humu.20308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16511828">Du et al. (2006)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10653325+16511828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WISKOTT-ALDRICH SYNDROME, SOMATIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, 1A-T
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776742 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776742;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=rs587776742" 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=rs587776742" 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=RCV000011869" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011869" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011869</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the somatic 1A-T mutation in the WAS gene that was found in compound heterozygous state in a patient with Wiskott-Aldrich syndrome (WAS; <a href="/entry/301000">301000</a>) by <a href="#17" class="mim-tip-reference" title="Du, W., Kumaki, S., Uchiyama, T., Yachie, A., Looi, C. Y., Kawai, S., Minegishi, M., Ramesh, N., Geha, R. S., Sasahara, Y., Tsuchiya, S. <strong>A second-site mutation in the initiation codon of WAS (WASP) results in expansion of subsets of lymphocytes in an Wiskott-Aldrich syndrome patient.</strong> Hum. Mutat. 27: 370-375, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16511828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16511828</a>] [<a href="https://doi.org/10.1002/humu.20308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16511828">Du et al. (2006)</a>, see <a href="#0019">300392.0019</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16511828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, 2-BP DEL, 73AC
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1602176299 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1602176299;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=rs1602176299" 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=rs1602176299" 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=RCV000011883" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011883" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011883</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an affected grandson of a female first cousin of the 3 patients described originally by <a href="#66" class="mim-tip-reference" title="Wiskott, A. <strong>Familiarer, angeborener Morbus Werlhofii?</strong> Mschr. Kinderheilk. 68: 212-216, 1937."None>Wiskott (1937)</a> with Wiskott-Aldrich syndrome (WAS; <a href="/entry/301000">301000</a>), <a href="#6" class="mim-tip-reference" title="Binder, V., Albert, M. H., Kabus, M., Bertone, M., Meindl, A., Belohradsky, B. H. <strong>The genotype of the original Wiskott phenotype.</strong> New Eng. J. Med. 355: 1790-1793, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17065640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17065640</a>] [<a href="https://doi.org/10.1056/NEJMoa062520" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17065640">Binder et al. (2006)</a> found a deletion of 2 nucleotides at positions 73 and 74 in exon 1 (coding sequence, 73-74delAC; the first nucleotide is the A of the ATG translation initiation codon) of the WAS gene. The deletion resulted in a frameshift that starts with amino acid 25; the shifted reading frame was open for another 11 amino acids before it resulted in a stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17065640" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, 1-BP DEL, 758A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2147264989 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2147264989;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=rs2147264989" 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=rs2147264989" 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=RCV001566101 OR RCV002463367" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001566101, RCV002463367" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001566101...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 15-year-old boy with Wiskott-Aldrich syndrome (WAS; <a href="/entry/301000">301000</a>), <a href="#16" class="mim-tip-reference" title="Dobbs, A. K., Yang, T., Farmer, D. M., Howard, V., Conley, M. E. <strong>A possible bichromatid mutation in a male gamete giving rise to a female mosaic for two different mutations in the X-linked gene WAS.</strong> Clin. Genet. 71: 171-176, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17250667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17250667</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00748.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17250667">Dobbs et al. (2007)</a> identified a 1-bp deletion (758delA) in codon 242 of exon 7 of the WAS gene. The proband had 2 affected maternal cousins who were found to have a different but contiguous single basepair deletion, a C deletion in codon 241 of exon 7 (<a href="#0023">300392.0023</a>). The mother of the proband was heterozygous for the A deletion, whereas her 3 sisters, including the mother of the affected cousins, were heterozygous for the C deletion. Their maternal grandmother was found to be a mosaic for deletions, which both occurred on the haplotype from the unaffected maternal great-grandfather, consistent with a bichromatid mutation in a male gamete. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17250667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, 1-BP DEL, CODON 241, C
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2147264981 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2147264981;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=rs2147264981" 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=rs2147264981" 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=RCV001390444 OR RCV001552729 OR RCV002463366" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001390444, RCV001552729, RCV002463366" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001390444...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 15-year-old boy with Wiskott-Aldrich syndrome (WAS; <a href="/entry/301000">301000</a>), <a href="#16" class="mim-tip-reference" title="Dobbs, A. K., Yang, T., Farmer, D. M., Howard, V., Conley, M. E. <strong>A possible bichromatid mutation in a male gamete giving rise to a female mosaic for two different mutations in the X-linked gene WAS.</strong> Clin. Genet. 71: 171-176, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17250667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17250667</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00748.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17250667">Dobbs et al. (2007)</a> identified a 1-bp deletion (758delA; <a href="#0022">300392.0022</a>) in codon 242 of exon 7 of the WAS gene. The proband had 2 affected maternal cousins who were found to have a different but contiguous single basepair deletion, a C deletion in codon 241 of exon 7 (<a href="#0023">300392.0023</a>). The mother of the proband was heterozygous for the A deletion, whereas her 3 sisters, including the mother of the affected cousins, were heterozygous for the C deletion. Their maternal grandmother was found to be a mosaic for deletions, which both occurred on the haplotype from the unaffected maternal great-grandfather, consistent with a bichromatid mutation in a male gamete. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17250667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 NEUTROPENIA, SEVERE CONGENITAL, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, SER272PRO
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906716 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906716;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=rs387906716" 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=rs387906716" 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=RCV000022858 OR RCV003764631" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022858, RCV003764631" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022858...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with severe congenital neutropenia (SCNX; <a href="/entry/300299">300299</a>), <a href="#2" class="mim-tip-reference" title="Ancliff, P. J., Blundell, M. P., Cory, G. O., Calle, Y., Worth, A., Kempski, H., Burns, S., Jones, G. E., Sinclair, J., Kinnon, C., Hann, I. M., Gale, R. E., Linch, D. C., Thrasher, A. J. <strong>Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia.</strong> Blood 108: 2182-2189, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16804117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16804117</a>] [<a href="https://doi.org/10.1182/blood-2006-01-010249" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16804117">Ancliff et al. (2006)</a> identified a T-to-C transition in the WAS gene, resulting in a ser272-to-pro (S272P) substitution in the GTPase-binding domain. The mutation was not detected in 50 controls. His mother, maternal aunt, and maternal grandmother were carriers of the mutation, and all had apparent nonrandom X-inactivation with 98%, 85%, and 79% expression, respectively, of the wildtype allele. Functional analysis revealed that the S272P mutation resulted in increased WAS activity and produced marked abnormalities of cytoskeletal structure and dynamics. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16804117" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 NEUTROPENIA, SEVERE CONGENITAL, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WAS, ILE294THR
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906717 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906717;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=rs387906717" 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=rs387906717" 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=RCV000022859 OR RCV001058962 OR RCV001268500 OR RCV003407355 OR RCV004782021" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022859, RCV001058962, RCV001268500, RCV003407355, RCV004782021" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022859...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy of Zairian parentage with severe congenital neutropenia (SCNX; <a href="/entry/300299">300299</a>), <a href="#2" class="mim-tip-reference" title="Ancliff, P. J., Blundell, M. P., Cory, G. O., Calle, Y., Worth, A., Kempski, H., Burns, S., Jones, G. E., Sinclair, J., Kinnon, C., Hann, I. M., Gale, R. E., Linch, D. C., Thrasher, A. J. <strong>Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia.</strong> Blood 108: 2182-2189, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16804117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16804117</a>] [<a href="https://doi.org/10.1182/blood-2006-01-010249" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16804117">Ancliff et al. (2006)</a> identified a T-to-C transition in the WAS gene, resulting in an ile294-to-thr (I294T) substitution in the GTPase-binding domain. The mutation was not detected in 100 randomly chosen controls or in 100 individuals of African origin. The X-chromosome inactivation pattern of his carrier mother showed a mean ratio of 79%:21% (wildtype:mutant alleles), with no significant differences between the inactivation pattern in purified neutrophils and CD3(+) cells. Functional analysis revealed that the I294T mutation resulted in increased WAS activity and produced marked abnormalities of cytoskeletal structure and dynamics. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16804117" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 males and carrier females from a large Irish kindred segregating X-linked congenital neutropenia, originally reported by <a href="#10" class="mim-tip-reference" title="Cryan, E. F., Deasy, P. F., Buckley, R. J., Greally, J. F. <strong>Congenital neutropenia and low serum immunoglobulin A: description and investigation of a large kindred.</strong> Thymus 11: 185-199, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3284030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3284030</a>]" pmid="3284030">Cryan et al. (1988)</a>, <a href="#5" class="mim-tip-reference" title="Beel, K., Cotter, M. M., Blatny, J., Bond, J., Lucus, G., Green, F., Vanduppen, V., Leung, D. W., Rooney, S., Smith, O. P., Rosen, M. K., Vandenberghe, P. <strong>A large kindred with X-linked neutropenia with an I294T mutation of the Wiskott-Aldrich syndrome gene.</strong> Brit. J. Haemat. 144: 120-126, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19006568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19006568</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19006568[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/10.1111/j.1365-2141.2008.07416.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19006568">Beel et al. (2008)</a> identified an 882T-C transition in exon 9 of the WAS gene, resulting in the I294T mutation. Functional analysis confirmed that the I294T mutant is constitutively active toward actin polymerization. Four of 6 female carriers showed random X-chromosome inactivation. Two female carriers showed no consistent pattern of asymmetric X-chromosome inactivation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3284030+19006568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#Aldrich1954" class="mim-tip-reference" title="Aldrich, R. A., Steinberg, A. G., Campbell, D. C. <strong>Pedigree demonstrating a sex-linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea.</strong> Pediatrics 13: 133-139, 1954.">Aldrich et al. (1954)</a>; <a href="#Greer1989" class="mim-tip-reference" title="Greer, W. L., Mahtani, M. M., Kwong, P. C., Rubin, L. A., Peacocke, M., Willard, H. F., Siminovitch, K. A. <strong>Linkage studies of the Wiskott-Aldrich syndrome: polymorphisms at TIMP and the X chromosome centromere are informative markers for genetic prediction.</strong> Hum. Genet. 83: 227-230, 1989.">Greer et al. (1989)</a>; <a href="#Greer1990" class="mim-tip-reference" title="Greer, W. L., Somani, A.-K., Kwong, P. C., Peacocke, M., Rubin, L. A., Siminovitch, K. A. <strong>Linkage relationships of the Wiskott-Aldrich syndrome to 10 loci in the pericentromeric region of the human X chromosome.</strong> Genomics 6: 568-571, 1990.">Greer et al. (1990)</a>; <a href="#Kwan1989" class="mim-tip-reference" title="Kwan, S.-P., Lehner, T., Lu, B., Raghu, G., Blaese, M., Sandkuyl, L. A., Ott, J., Fraser, N., Boyd, Y., Craig, I. W., Fischer, S., Rosen, F. <strong>Linkage of DXS255 to the Wiskott Aldrich syndrome gene. (Abstract)</strong> Cytogenet. Cell Genet. 51: 1027 only, 1989.">Kwan
|
|
et al. (1989)</a>; <a href="#Kwan1988" class="mim-tip-reference" title="Kwan, S.-P., Sandkuyl, L. A., Blaese, M., Kunkel, L. M., Bruns, G., Parmley, R., Skarshaug, S., Page, D. C., Ott, J., Rosen, F. S. <strong>Genetic mapping of the Wiskott-Aldrich syndrome with two highly-linked polymorphic DNA markers.</strong> Genomics 3: 39-43, 1988.">Kwan et al. (1988)</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="Aldrich1954" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Aldrich, R. A., Steinberg, A. G., Campbell, D. C.
|
|
<strong>Pedigree demonstrating a sex-linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea.</strong>
|
|
Pediatrics 13: 133-139, 1954.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13133561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13133561</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13133561" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Ancliff2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ancliff, P. J., Blundell, M. P., Cory, G. O., Calle, Y., Worth, A., Kempski, H., Burns, S., Jones, G. E., Sinclair, J., Kinnon, C., Hann, I. M., Gale, R. E., Linch, D. C., Thrasher, A. J.
|
|
<strong>Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia.</strong>
|
|
Blood 108: 2182-2189, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16804117/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16804117</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16804117" 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-2006-01-010249" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Andreu2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Andreu, N., Carreras, C., Prieto, F., Estivill, X., Volpini, V., Fillat, C.
|
|
<strong>Identification and characterization of a novel splice-site mutation in a patient with Wiskott-Aldrich syndrome.</strong>
|
|
J. Hum. Genet. 48: 590-593, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14566484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14566484</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14566484" 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/s10038-003-0083-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Ariga1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ariga, T., Yamada, M., Sakiyama, Y., Tatsuzawa, O.
|
|
<strong>A case of Wiskott-Aldrich syndrome with dual mutations in exon 10 of the WASP gene: an additional de novo one-base insertion, which restores frame shift due to an inherent one-base deletion, detected in the major population of the patient's peripheral blood lymphocytes. (Letter)</strong>
|
|
Blood 92: 699-701, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9657775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9657775</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9657775" 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="Beel2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Beel, K., Cotter, M. M., Blatny, J., Bond, J., Lucus, G., Green, F., Vanduppen, V., Leung, D. W., Rooney, S., Smith, O. P., Rosen, M. K., Vandenberghe, P.
|
|
<strong>A large kindred with X-linked neutropenia with an I294T mutation of the Wiskott-Aldrich syndrome gene.</strong>
|
|
Brit. J. Haemat. 144: 120-126, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19006568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19006568</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19006568[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=19006568" 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.1365-2141.2008.07416.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Binder2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Binder, V., Albert, M. H., Kabus, M., Bertone, M., Meindl, A., Belohradsky, B. H.
|
|
<strong>The genotype of the original Wiskott phenotype.</strong>
|
|
New Eng. J. Med. 355: 1790-1793, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17065640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17065640</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17065640" 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/NEJMoa062520" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Boztug2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Boztug, K., Germeshausen, M., Avedillo Diez, I., Gulacsy, V., Diestelhorst, J., Ballmaier, M., Welte, K., Marodi, L., Chernyshova, L. I., Klein, C.
|
|
<strong>Multiple independent second-site mutations in two siblings with somatic mosaicism for Wiskott-Aldrich syndrome.</strong>
|
|
Clin. Genet. 74: 68-74, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18479478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18479478</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18479478" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2008.01019.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Cheng2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cheng, H.-C., Skehan, B. M., Campellone, K. G., Leong, J. M., Rosen, M, K.
|
|
<strong>Structural mechanism of WASP activation by the enterohaemorrhagic E. coli effector EspFU.</strong>
|
|
Nature 454: 1009-1013, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18650809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18650809</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18650809[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=18650809" 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/nature07160" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Cotta-de-Almeida2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cotta-de-Almeida, V., Westerberg, L., Maillard, M. H., Onaldi, D., Wachtel, H., Meelu, P., Chung, U., Xavier, R., Alt, F. W., Snapper, S. B.
|
|
<strong>Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 15424-15429, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17878299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17878299</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17878299[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=17878299" 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.0706881104" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Cryan1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cryan, E. F., Deasy, P. F., Buckley, R. J., Greally, J. F.
|
|
<strong>Congenital neutropenia and low serum immunoglobulin A: description and investigation of a large kindred.</strong>
|
|
Thymus 11: 185-199, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3284030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3284030</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3284030" 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="11" class="mim-anchor"></a>
|
|
<a id="de Saint Basile1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Saint Basile, G., Lagelouse, R. D., Lambert, N., Schwarz, K., Le Mareck, B., Odent, S., Schlegel, N., Fischer, A.
|
|
<strong>Isolated X-linked thrombocytopenia in two unrelated families is associated with point mutations in the Wiskott-Aldrich syndrome protein gene.</strong>
|
|
J. Pediat. 129: 56-62, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8757563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8757563</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8757563" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0022-3476(96)70190-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Derry1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Derry, J. M. J., Kerns, J. A., Weinberg, K. I., Ochs, H. D., Volpini, V., Estivill, X., Walker, A. P., Francke, U.
|
|
<strong>WASP gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia.</strong>
|
|
Hum. Molec. Genet. 4: 1127-1135, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528199</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8528199" 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/4.7.1127" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Derry1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Derry, J. M. J., Ochs, H. D., Francke, U.
|
|
<strong>Isolation of a novel gene mutated in Wiskott-Aldrich syndrome.</strong>
|
|
Cell 78: 635-644, 1994. Note: Erratum: Cell 79: following 922, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8069912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8069912</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8069912" 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(94)90528-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Derry1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Derry, J. M. J., Wiedemann, P., Blair, P., Wang, Y., Kerns, J. A., Lemahieu, V., Godfrey, V. L., Wilkinson, J. E., Francke, U.
|
|
<strong>The mouse homolog of the Wiskott-Aldrich syndrome protein (WASP) gene is highly conserved and maps near the scurfy (sf) mutation on the X chromosome.</strong>
|
|
Genomics 29: 471-477, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8666397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8666397</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8666397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1995.9979" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Devriendt2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Devriendt, K., Kim, A. S., Mathijs, G., Frints, S. G. M., Schwartz, M., Van den Oord, J. J., Verhoef, G. E. G., Boogaerts, M. A., Fryns, J.-P., You, D., Rosen, M. K., Vandenberghe, P.
|
|
<strong>Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia.</strong>
|
|
Nature Genet. 27: 313-317, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11242115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11242115</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11242115" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/85886" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Dobbs2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dobbs, A. K., Yang, T., Farmer, D. M., Howard, V., Conley, M. E.
|
|
<strong>A possible bichromatid mutation in a male gamete giving rise to a female mosaic for two different mutations in the X-linked gene WAS.</strong>
|
|
Clin. Genet. 71: 171-176, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17250667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17250667</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17250667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2007.00748.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Du2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Du, W., Kumaki, S., Uchiyama, T., Yachie, A., Looi, C. Y., Kawai, S., Minegishi, M., Ramesh, N., Geha, R. S., Sasahara, Y., Tsuchiya, S.
|
|
<strong>A second-site mutation in the initiation codon of WAS (WASP) results in expansion of subsets of lymphocytes in an Wiskott-Aldrich syndrome patient.</strong>
|
|
Hum. Mutat. 27: 370-375, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16511828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16511828</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16511828" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.20308" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Fillat2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fillat, C., Espanol, T., Oset, M., Ferrando, M., Estivill, X., Volpini, V.
|
|
<strong>Identification of WASP mutations in 14 Spanish families with Wiskott-Aldrich syndrome.</strong>
|
|
Am. J. Med. Genet. 100: 116-121, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11298372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11298372</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11298372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.1228" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Greer1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Greer, W. L., Mahtani, M. M., Kwong, P. C., Rubin, L. A., Peacocke, M., Willard, H. F., Siminovitch, K. A.
|
|
<strong>Linkage studies of the Wiskott-Aldrich syndrome: polymorphisms at TIMP and the X chromosome centromere are informative markers for genetic prediction.</strong>
|
|
Hum. Genet. 83: 227-230, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2571560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2571560</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2571560" 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/BF00285161" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Greer1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Greer, W. L., Shehabeldin, A., Schulman, J., Junker, A., Siminovitch, K. A.
|
|
<strong>Identification of WASP mutations, mutation hotspots and genotype-phenotype disparities in 24 patients with the Wiskott-Aldrich syndrome.</strong>
|
|
Hum. Genet. 98: 685-690, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8931701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8931701</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8931701" 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/s004390050285" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Greer1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Greer, W. L., Somani, A.-K., Kwong, P. C., Peacocke, M., Rubin, L. A., Siminovitch, K. A.
|
|
<strong>Linkage relationships of the Wiskott-Aldrich syndrome to 10 loci in the pericentromeric region of the human X chromosome.</strong>
|
|
Genomics 6: 568-571, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2328995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2328995</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2328995" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(90)90489-h" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Hirschhorn1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hirschhorn, R., Yang, D. R., Puck, J. M., Huie, M. L., Jiang, C.-K., Kurlandsky, L. E.
|
|
<strong>Spontaneous in vivo reversion to normal of an inherited mutation in a patient with adenosine deaminase deficiency.</strong>
|
|
Nature Genet. 13: 290-295, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673127</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8673127" 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/ng0796-290" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Ho2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ho, L. L., Ayling, J., Prosser, I., Kronenberg, H., Iland, H., Joshua, D.
|
|
<strong>Missense C168T in the Wiskott-Aldrich syndrome protein gene is a common mutation in X-linked thrombocytopenia.</strong>
|
|
Brit. J. Haemat. 112: 76-80, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11167787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11167787</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11167787" 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.1365-2141.2001.02465.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Humblet-Baron2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Humblet-Baron, S., Sather, B., Anover, S., Becker-Herman, S., Kasprowicz, D. J., Khim, S., Nguyen, T., Hudkins-Loya, K., Alpers, C. E., Ziegler, S. F., Ochs, H., Torgerson, T., Campbell, D. J., Rawlings, D. J.
|
|
<strong>Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis.</strong>
|
|
J. Clin. Invest. 117: 407-418, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17218989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17218989</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17218989[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=17218989" 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/JCI29539" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Imai2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Imai, K., Morio, T., Zhu, Y., Jin, Y., Itoh, S., Kajiwara, M., Yata, J., Mizutani, S., Ochs, H. D., Nonoyama, S.
|
|
<strong>Clinical course of patients with WASP gene mutations.</strong>
|
|
Blood 103: 456-464, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12969986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12969986</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12969986" 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-2003-05-1480" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Inoue2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Inoue, H., Kurosawa, H., Nonoyama, S., Imai, K., Kumazaki, H., Matsunaga, T., Sato, Y., Sugita, K., Eguchi, M.
|
|
<strong>X-linked thrombocytopenia in a girl.</strong>
|
|
Brit. J. Haemat. 118: 1163-1165, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12199801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12199801</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12199801" 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.1365-2141.2002.03740.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Jin2004" class="mim-anchor"></a>
|
|
<div class="mim-changed mim-change">
|
|
<p class="mim-text-font">
|
|
Jin, Y., Mazza, C., Christie, J. R., Giliani, S., Fiorini, M., Mella, P., Gandellini, F., Stewart, D. M., Zhu, Q., Nelson, D. L., Notarangelo, L. D., Ochs, H. D.
|
|
<strong>Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation.</strong>
|
|
Blood 104: 4010-4019, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15284122/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15284122</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15284122" 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-2003-05-1592" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Kim2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kim, A. S., Kakalis, L. T., Abdul-Manan, N., Liu, G. A., Rosen, M. K.
|
|
<strong>Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein.</strong>
|
|
Nature 404: 151-158, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10724160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10724160</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10724160" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/35004513" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Kolluri1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kolluri, R., Shehabeldin, A., Peacocke, M., Lamhonwah, A.-M., Teichert-Kuliszewska, K., Weissman, S. M., Siminovitch, K. A.
|
|
<strong>Identification of WASP mutations in patients with Wiskott-Aldrich syndrome and isolated thrombocytopenia reveals allelic heterogeneity at the WAS locus.</strong>
|
|
Hum. Molec. Genet. 4: 1119-1126, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8528198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8528198</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8528198" 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/4.7.1119" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Kolluri1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kolluri, R., Tolias, K. F., Carpenter, C. L., Rosen, F. S., Kirchhausen, T.
|
|
<strong>Direct interaction of the Wiskott-Aldrich syndrome protein with the GTPase Cdc42.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 5615-5618, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8643625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8643625</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8643625" 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.93.11.5615" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Kwan1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kwan, S. P., Hagemann, T. L., Blaese, R. M., Knutsen, A., Rosen, F. S.
|
|
<strong>Scanning of the Wiskott-Aldrich syndrome (WAS) gene: identification of 18 novel alterations including a possible mutation hotspot at Arg86 resulting in thrombocytopenia, a mild WAS phenotype.</strong>
|
|
Hum. Molec. Genet. 4: 1995-1998, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8595430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8595430</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8595430" 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/4.10.1995" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Kwan1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kwan, S.-P., Hagemann, T. L., Radtke, B. E., Blaese, R. M., Rosen, F. S.
|
|
<strong>Identification of mutations in the Wiskott-Aldrich syndrome gene and characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent to the disease gene.</strong>
|
|
Proc. Nat. Acad. Sci. 92: 4706-4710, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7753869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7753869</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7753869" 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.92.10.4706" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Kwan1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kwan, S.-P., Lehner, T., Lu, B., Raghu, G., Blaese, M., Sandkuyl, L. A., Ott, J., Fraser, N., Boyd, Y., Craig, I. W., Fischer, S., Rosen, F.
|
|
<strong>Linkage of DXS255 to the Wiskott Aldrich syndrome gene. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 51: 1027 only, 1989.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Kwan1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kwan, S.-P., Sandkuyl, L. A., Blaese, M., Kunkel, L. M., Bruns, G., Parmley, R., Skarshaug, S., Page, D. C., Ott, J., Rosen, F. S.
|
|
<strong>Genetic mapping of the Wiskott-Aldrich syndrome with two highly-linked polymorphic DNA markers.</strong>
|
|
Genomics 3: 39-43, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2906042/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2906042</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2906042" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(88)90156-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Lemahieu1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lemahieu, V., Gastier, J. M., Francke, U.
|
|
<strong>Novel mutations in the Wiskott-Aldrich syndrome protein gene and their effects on transcriptional, translational, and clinical phenotypes.</strong>
|
|
Hum. Mutat. 14: 54-66, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10447259/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10447259</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10447259" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)14:1<54::AID-HUMU7>3.0.CO;2-E" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Lutskiy2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lutskiy, M. I., Jones, L. N., Rosen, F. S., Remold-O'Donnell, E.
|
|
<strong>An Alu-mediated deletion at Xp11.23 leading to Wiskott-Aldrich syndrome.</strong>
|
|
Hum. Genet. 110: 515-519, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12073025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12073025</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12073025" 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/s00439-002-0716-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Lutskiy2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lutskiy, M. I., Sasahara, Y., Kenney, D. M., Rosen, F. S., Remold-O'Donnell, E.
|
|
<strong>Wiskott-Aldrich syndrome in a female.</strong>
|
|
Blood 100: 2763-2768, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12351383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12351383</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12351383" 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-2002-02-0388" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Lyon1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lyon, M. F., Peters, J., Glenister, P. H., Ball, S., Wright, E.
|
|
<strong>The scurfy mouse mutant has previously unrecognized hematological abnormalities and resembles Wiskott-Aldrich syndrome.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 2433-2437, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2320565/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2320565</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2320565" 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.87.7.2433" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Maillard2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maillard, M. H., Cotta-de-Almeida, V., Takeshima, F., Nguyen, D. D., Michetti, P., Nagler, C., Bhan, A. K., Snapper, S. B.
|
|
<strong>The Wiskott-Aldrich syndrome protein is required for the function of CD4+CD25+Foxp3+ regulatory T cells.</strong>
|
|
J. Exp. Med. 204: 381-391, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17296786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17296786</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17296786[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=17296786" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1084/jem.20061338" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Marangoni2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Marangoni, F., Trifari, S., Scaramuzza, S., Panaroni, C., Martino, S., Notarangelo, L. D., Baz, Z., Metin, A., Cattaneo, F., Villa, A., Aiuti, A., Battaglia, M., Roncarolo, M.-G., Dupre, L.
|
|
<strong>WASP regulates suppressor activity of human and murine CD4+CD25+FOXP3+ natural regulatory T cells.</strong>
|
|
J. Exp. Med. 204: 369-380, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17296785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17296785</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17296785[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=17296785" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1084/jem.20061334" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Marchand2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Marchand, J.-B., Kaiser, D. A., Pollard, T. D., Higgs, H. N.
|
|
<strong>Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex.</strong>
|
|
Nature Cell Biol. 3: 76-82, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11146629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11146629</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11146629" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/35050590" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Notarangelo2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Notarangelo, L. D., Mazza, C., Giliani, S., D'Aria, C., Gandellini, F., Ravelli, C., Locatelli, M. G., Nelson, D. L., Ochs, H. D., Notarangelo, L. D.
|
|
<strong>Missense mutations of the WASP gene cause intermittent X-linked thrombocytopenia.</strong>
|
|
Blood 99: 2268-2269, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11877312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11877312</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11877312" 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.v99.6.2268" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Orange2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Orange, J. S., Ramesh, N., Remold-O'Donnell, E., Sasahara, Y., Koopman, L., Byrne, M., Bonilla, F. A., Rosen, F. S., Geha, R. S., Strominger, J. L.
|
|
<strong>Wiskott-Aldrich syndrome protein is required for NK cell cytotoxicity and colocalizes with actin to NK cell-activating immunologic synapses.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 11351-11356, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12177428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12177428</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12177428[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=12177428" 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.162376099" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Parolini1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Parolini, O., Ressmann, G., Haas, O. A., Pawlowsky, J., Gadner, H., Knapp, W., Holter, W.
|
|
<strong>X-linked Wiskott-Aldrich syndrome in a girl.</strong>
|
|
New Eng. J. Med. 338: 291-295, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9445409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9445409</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9445409" 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/NEJM199801293380504" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Puck1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Puck, J. M., Willard, H. F.
|
|
<strong>X inactivation in females with X-linked disease.</strong>
|
|
New Eng. J. Med. 338: 325-327, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9445416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9445416</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9445416" 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/NEJM199801293380611" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Sasahara2000" class="mim-anchor"></a>
|
|
<div class="mim-changed mim-change">
|
|
<p class="mim-text-font">
|
|
Sasahara, Y., Kawai, S., Kumaki, S., Ohashi, Y., Minegishi, M., Tsuchiya, S.
|
|
<strong>Novel mutations, no detectable mRNA and familial genetic analysis of the Wiskott-Aldrich syndrome protein gene in six Japanese patients with Wiskott-Aldrich syndrome.</strong>
|
|
Europ. J. Pediat. 159: 23-30, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10653325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10653325</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10653325" 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/s004310050005" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Sasahara2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sasahara, Y., Rachid, R., Byrne, M. J., de la Fuente, M. A., Abraham, R. T., Ramesh, N., Geha, R. S.
|
|
<strong>Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation.</strong>
|
|
Molec. Cell 10: 1269-1281, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12504004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12504004</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12504004" 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/s1097-2765(02)00728-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Schindelhauer1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schindelhauer, D., Weiss, M., Hellebrand, H., Golla, A., Hergersberg, M., Seger, R., Belohradsky, B. H., Meindl, A.
|
|
<strong>Wiskott-Aldrich syndrome: no strict genotype-phenotype correlations but clustering of missense mutations in the amino-terminal part of the WASP gene product.</strong>
|
|
Hum. Genet. 98: 68-76, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8682510/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8682510</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8682510" 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/s004390050162" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Scott2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scott, M. P., Zappacosta, F., Kim, E. Y., Annan, R. S., Miller, W. T.
|
|
<strong>Identification of novel SH3 domain ligands for the Src family kinase Hck: Wiskott-Aldrich syndrome protein (WASP), WASP-interacting protein (WIP), and ELMO1.</strong>
|
|
J. Biol. Chem. 277: 28238-28246, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12029088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12029088</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12029088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M202783200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="50" class="mim-anchor"></a>
|
|
<a id="Siminovitch1995" class="mim-anchor"></a>
|
|
<div class="mim-changed mim-change">
|
|
<p class="mim-text-font">
|
|
Siminovitch, K. A., Greer, W. L., Novogrodsky, A., Axelsson, B., Somani, A.-K., Peacocke, M.
|
|
<strong>A diagnostic assay for the Wiskott-Aldrich syndrome and its variant forms.</strong>
|
|
J. Investig. Med. 43: 159-169, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7735919/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7735919</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7735919" 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="51" class="mim-anchor"></a>
|
|
<a id="Snapper1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Snapper, S. B., Rosen, F. S., Mizoguchi, E., Cohen, P., Khan, W., Liu, C. H., Hagemann, T. L., Kwan, S. P., Ferrini, R., Davidson, L., Bhan, A. K., Alt, F. W.
|
|
<strong>Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation.</strong>
|
|
Immunity 9: 81-91, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9697838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9697838</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9697838" 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/s1074-7613(00)80590-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Snapper1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Snapper, S. B., Rosen, F. S.
|
|
<strong>The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization.</strong>
|
|
Annu. Rev. Immun. 17: 905-929, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10358777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10358777</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10358777" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1146/annurev.immunol.17.1.905" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Stewart1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stewart, D. M., Treiber-Held, S., Kurman, C. C., Facchetti, F., Notarangelo, L. D., Nelson, D. L.
|
|
<strong>Studies of the expression of the Wiskott-Aldrich syndrome protein.</strong>
|
|
J. Clin. Invest. 97: 2627-2634, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8647957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8647957</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8647957" 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/JCI118712" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Symons1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Symons, M., Derry, J. M. J., Karlak, B., Jiang, S., Lemahieu, V., McCormick, F., Francke, U., Abo, A.
|
|
<strong>Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization.</strong>
|
|
Cell 84: 723-734, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8625410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8625410</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8625410" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0092-8674(00)81050-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Thompson1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thompson, L. J., Lalloz, M. R. A., Layton, D. M.
|
|
<strong>Unique and recurrent WAS gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia.</strong>
|
|
Blood Cells Molec. Dis. 25: 218-226, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10575547/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10575547</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10575547" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/bcmd.1999.0247" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="56" class="mim-anchor"></a>
|
|
<a id="Vallee2024" class="mim-anchor"></a>
|
|
<div class="mim-changed mim-change">
|
|
<p class="mim-text-font">
|
|
Vallee, T. C., Glasmacher, J. S., Buchner, H., Arkwright, P. D., Behrends, U., Bondarenko, A., Browning, M. J., Buchbinder, D., Cattoni, A., Chernyshova, L., Ciznar, P., Cole, T., and 43 others.
|
|
<strong>Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival.</strong>
|
|
Blood 143: 2504-2516, 2024.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38579284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38579284</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38579284" 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.2023021411" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="57" class="mim-anchor"></a>
|
|
<a id="Villa1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Villa, A., Notarangelo, L., Macchi, P., Mantuano, E., Cavagni, G., Brugnoni, D., Strina, D., Patrosso, M. C., Ramenghi, U., Sacco, M. G., Ugazio, A., Vezzoni, P.
|
|
<strong>X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene.</strong>
|
|
Nature Genet. 9: 414-417, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7795648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7795648</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7795648" 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/ng0495-414" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="58" class="mim-anchor"></a>
|
|
<a id="Volkman2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Volkman, B. F., Prehoda, K. E., Scott, J. A., Peterson, F. C., Lim, W. A.
|
|
<strong>Structure of the N-WASP EVH1 domain-WIP complex: insight into the molecular basis of Wiskott-Aldrich syndrome.</strong>
|
|
Cell 111: 565-576, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12437929/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12437929</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12437929" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0092-8674(02)01076-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="59" class="mim-anchor"></a>
|
|
<a id="Wada2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wada, T., Konno, A., Schurman, S. H., Garabedian, E. K., Anderson, S. M., Kirby, M., Nelson, D. L., Candotti, F.
|
|
<strong>Second-site mutation in the Wiskott-Aldrich syndrome (WAS) protein gene causes somatic mosaicism in two WAS siblings.</strong>
|
|
J. Clin. Invest. 111: 1389-1397, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12727931/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12727931</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12727931[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=12727931" 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/JCI15485" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="60" class="mim-anchor"></a>
|
|
<a id="Wada2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wada, T., Schurman, S. H., Jagadeesh, G. J., Garabedian, E. K., Nelson, D. L., Candotti, F.
|
|
<strong>Multiple patients with revertant mosaicism in a single Wiskott-Aldrich syndrome family.</strong>
|
|
Blood 104: 1270-1272, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15142877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15142877</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15142877" 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-2004-03-0846" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="61" class="mim-anchor"></a>
|
|
<a id="Wada2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wada, T., Schurman, S. H., Otsu, M., Garabedian, E. K., Ochs, H. D., Nelson, D. L., Candotti, F.
|
|
<strong>Somatic mosaicism in Wiskott-Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism.</strong>
|
|
Proc. Nat. Acad. Sci. 98: 8697-8702, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11447283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11447283</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11447283[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=11447283" 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.151260498" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="62" class="mim-anchor"></a>
|
|
<a id="Waisfisz1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Waisfisz, Q., Morgan, N. V., Savino, M., de Winter, J. P., van Berkel, C. G. M., Hoatlin, M. E., Ianzano, L., Gibson, R. A., Arwert, F., Savoia, A., Mathew, C. G., Pronk, J. C., Joenje, H.
|
|
<strong>Spontaneous functional correction of homozygous Fanconi anaemia alleles reveals novel mechanistic basis for reverse mosaicism.</strong>
|
|
Nature Genet. 22: 379-383, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10431244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10431244</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10431244" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/11956" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="63" class="mim-anchor"></a>
|
|
<a id="Wengler1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wengler, G., Gorlin, J. B., Williamson, J. M., Rosen, F. S., Bing, D. H.
|
|
<strong>Nonrandom inactivation of the X chromosome in early lineage hematopoietic cells in carriers of Wiskott-Aldrich syndrome.</strong>
|
|
Blood 85: 2471-2477, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7537115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7537115</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7537115" 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="Wengler1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wengler, G. S., Notarangelo, L. D., Berardelli, S., Pollonni, G., Mella, P., Fasth, A., Ugazio, A. G., Parolini, O.
|
|
<strong>High prevalence of nonsense, frame shift, and splice-site mutations in 16 patients with full-blown Wiskott-Aldrich syndrome.</strong>
|
|
Blood 86: 3648-3654, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7579329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7579329</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7579329" 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="Westerberg2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Westerberg, L. S., Meelu, P., Baptista, M., Eston, M. A., Adamovich, D. A., Cotta-de-Almeida, V., Seed, B., Rosen, M. K., Vandenberghe, P., Thrasher, A. J., Klein, C., Alt, F. W., Snapper, S. B.
|
|
<strong>Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes.</strong>
|
|
J. Exp. Med. 207: 1145-1152, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20513746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20513746</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20513746[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=20513746" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1084/jem.20091245" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="66" class="mim-anchor"></a>
|
|
<a id="Wiskott1937" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wiskott, A.
|
|
<strong>Familiarer, angeborener Morbus Werlhofii?</strong>
|
|
Mschr. Kinderheilk. 68: 212-216, 1937.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="67" class="mim-anchor"></a>
|
|
<a id="Zhu1997" class="mim-anchor"></a>
|
|
<div class="mim-changed mim-change">
|
|
<p class="mim-text-font">
|
|
Zhu, Q., Watanabe, C., Liu, T., Hollenbaugh, D., Blaese, R. M., Kanner, S. B., Aruffo, A., Ochs, H. D.
|
|
<strong>Wiskott-Aldrich syndrome/X-linked thrombocytopenia: WASP gene mutations, protein expression, and phenotype.</strong>
|
|
Blood 90: 2680-2689, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326235/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326235</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326235" 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="Zhu1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhu, Q., Zhang, M., Blaese, R. M., Derry, J. M. J., Junker, A., Francke, U., Chen, S.-H., Ochs, H. D.
|
|
<strong>The Wiskott-Aldrich syndrome and X-linked congenital thrombocytopenia are caused by mutations of the same gene.</strong>
|
|
Blood 86: 3797-3804, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7579347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7579347</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7579347" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</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">
|
|
Ada Hamosh - updated : 01/07/2025
|
|
</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">
|
|
Paul J. Converse - updated : 11/9/2012<br>Paul J. Converse - updated : 1/12/2012<br>Marla J. F. O'Neill - updated : 5/20/2011<br>Cassandra L. Kniffin - updated : 5/13/2009<br>Ada Hamosh - updated : 9/2/2008<br>Marla J. F. O'Neill - updated : 11/21/2007<br>Paul J. Converse - updated : 11/14/2007<br>Paul J. Converse - updated : 8/7/2007<br>Paul J. Converse - updated : 3/19/2007<br>Victor A. McKusick - updated : 11/30/2006<br>Anne M. Stumpf - updated : 6/13/2006<br>Victor A. McKusick - updated : 6/6/2006<br>Victor A. McKusick - updated : 12/10/2004<br>Victor A. McKusick - updated : 4/16/2004<br>Victor A. McKusick - updated : 12/23/2003<br>Stylianos E. Antonarakis - updated : 4/28/2003<br>Victor A. McKusick - updated : 1/10/2003<br>Stylianos E. Antonarakis - updated : 11/25/2002<br>Victor A. McKusick - updated : 10/21/2002<br>Victor A. McKusick - updated : 10/9/2002<br>Victor A. McKusick - updated : 6/7/2002<br>Victor A. McKusick - updated : 5/13/2002
|
|
</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 : 5/8/2002
|
|
</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 : 01/08/2025
|
|
</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">
|
|
alopez : 01/08/2025<br>alopez : 01/07/2025<br>carol : 03/11/2021<br>carol : 01/16/2018<br>alopez : 09/22/2016<br>terry : 03/28/2013<br>mgross : 11/19/2012<br>mgross : 11/19/2012<br>terry : 11/9/2012<br>carol : 3/26/2012<br>mgross : 2/23/2012<br>terry : 1/27/2012<br>mgross : 1/18/2012<br>terry : 1/12/2012<br>terry : 1/12/2012<br>wwang : 6/8/2011<br>wwang : 6/7/2011<br>carol : 6/7/2011<br>wwang : 5/25/2011<br>terry : 5/20/2011<br>wwang : 5/13/2009<br>alopez : 9/15/2008<br>terry : 9/2/2008<br>alopez : 4/23/2008<br>carol : 11/26/2007<br>terry : 11/21/2007<br>mgross : 11/15/2007<br>mgross : 11/15/2007<br>terry : 11/14/2007<br>mgross : 8/23/2007<br>terry : 8/7/2007<br>mgross : 3/22/2007<br>terry : 3/19/2007<br>alopez : 12/8/2006<br>terry : 11/30/2006<br>terry : 11/3/2006<br>joanna : 11/2/2006<br>alopez : 6/13/2006<br>terry : 6/6/2006<br>terry : 8/3/2005<br>tkritzer : 12/27/2004<br>terry : 12/10/2004<br>mgross : 12/6/2004<br>alopez : 4/20/2004<br>terry : 4/16/2004<br>tkritzer : 2/18/2004<br>carol : 12/24/2003<br>terry : 12/23/2003<br>mgross : 4/28/2003<br>tkritzer : 1/23/2003<br>tkritzer : 1/13/2003<br>terry : 1/10/2003<br>mgross : 11/25/2002<br>carol : 10/22/2002<br>tkritzer : 10/21/2002<br>tkritzer : 10/21/2002<br>tkritzer : 10/21/2002<br>tkritzer : 10/17/2002<br>tkritzer : 10/9/2002<br>tkritzer : 10/9/2002<br>alopez : 6/13/2002<br>terry : 6/7/2002<br>alopez : 5/21/2002<br>alopez : 5/21/2002<br>terry : 5/13/2002<br>carol : 5/13/2002<br>carol : 5/13/2002<br>ckniffin : 5/10/2002<br>ckniffin : 5/9/2002
|
|
</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> 300392
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
WASP ACTIN NUCLEATION PROMOTING FACTOR; WAS
|
|
|
|
</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">
|
|
WAS GENE<br />
|
|
WAS PROTEIN; WASP
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: WAS</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 36070007, 718882006;
|
|
|
|
|
|
<strong>ICD10CM:</strong> D82.0;
|
|
|
|
|
|
<strong>ICD9CM:</strong> 279.12;
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: Xp11.23
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : X:48,676,636-48,691,427 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="4">
|
|
<span class="mim-font">
|
|
Xp11.23
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Neutropenia, severe congenital, X-linked
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
300299
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
X-linked recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Thrombocytopenia, X-linked
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
313900
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
X-linked recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Thrombocytopenia, X-linked, intermittent
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
313900
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
X-linked recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Wiskott-Aldrich syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
301000
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
X-linked 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>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Studies of the Wiskott-Aldrich syndrome (WAS; 301000) led to the characterization and mapping of the WAS gene. To isolate the WAS gene, Derry et al. (1994) used a positional cloning strategy that involved the construction of a clone contig in the critical WAS region Xp11.23-p11.22, bounded by the markers DXS255 and TIMP, Evaluation of several candidate cDNAs led to the identification of a sequence whose expression was limited to lymphocytic and megakaryocytic cell lineages and which was altered in patients with Wiskott-Aldrich syndrome. Derry et al. (1994) referred to the gene as WASP and showed that it encodes a 501-amino acid proline-rich protein. In an erratum, Derry et al. (1994) stated that WASP contains 502 amino acids. </p><p>Derry et al. (1995) isolated and sequenced the mouse Wasp gene. The predicted amino acid sequence was found to be 86% identical to the human WASP sequence. The mouse gene is expressed as an mRNA of approximately 2.4 kb in thymus and spleen. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Kwan et al. (1995) updated the coding and genomic sequences of the WAS gene, reporting that it has 12 exons. </p><p>Derry et al. (1995) found that a distinctive feature of the mouse Wasp gene is an expanded polymorphic GGA trinucleotide repeat that codes for polyglycine and varies from 15 to 17 triplets in different mouse strains. The genomic structure of the mouse gene closely resembles that in the human with respect to exon/intron positions and intron lengths. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By positional cloning in the critical Wiskott-Aldrich syndrome region at chromosome Xp11.23-p11.22, Derry et al. (1994) identified the WAS gene. </p><p>Chromosomal mapping and interspecific backcross performed by Derry et al. (1995) placed the mouse Wasp locus near the centromere of the mouse X chromosome, inseparable from Gata1 (305371), Tcfe3 (314310), and 'scurfy' (sf). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Stewart et al. (1996) used monoclonal anti-WASP antibodies in Western immunoblots to show that WASP is present in the cytoplasmic but not the nuclear fraction of normal human peripheral blood mononuclear cells, platelets, T lymphocytes, non-T lymphocytes, and monocytes. WASP was present in 2 of 4 EBV-transformed cell lines from WAS patients. The failure to find WASP in the nucleus suggested to Stewart et al. (1996) that it is not a transcription factor. </p><p>Symons et al. (1996) reported that the Wiskott-Aldrich protein has a GTPase binding site and that it interacts specifically with activated CDC42 (116952), a member of the Rho-like GTPase family. They noted that WASP localizes in the cytoplasm in clusters that are enriched in polymerized actin. They proposed that WASP provides a link between CDC42 and the actin cytoskeleton. </p><p>T lymphocytes of males with WAS exhibit a severe disturbance of the actin cytoskeleton, suggesting that the WAS protein may regulate its organization. Kolluri et al. (1996) also showed that WAS protein interacts with CDC42 in a GTP-dependent manner. This interaction was detected in cell lysates, in transient transfections, and with purified recombinant proteins. Different mutant WAS proteins from 3 unrelated affected males retained their ability to interact with Cdc42 but the level of expression of the WAS protein in these mutants was only 2 to 5% of normal. These data suggested to Kolluri et al. (1996) that the WAS protein may function as a signal transduction adaptor downstream of Cdc42 and that, in affected males, the cytoskeletal abnormalities may result from a defect in Cdc42 signaling. </p><p>CDC42 can regulate the actin cytoskeleton through activation of WASP family members. Activation relieves an autoinhibitory contact between the GTPase-binding domain and the C-terminal region of WASP proteins. Kim et al. (2000) reported the autoinhibited structure of the GTPase-binding domain of WASP, which can be induced by the C-terminal region or by organic cosolvents. In the autoinhibited complex, intramolecular interactions with the GTPase-binding domain occlude residues of the C terminus that regulate the Arp2/3 actin-nucleating complex (see 604221). Binding of CDC42 to the GTPase-binding domain causes a dramatic conformational change, resulting in disruption of the hydrophobic core and release of the C terminus, enabling its interaction with the actin regulatory machinery. </p><p>Using fluorescence anisotropy analysis, Marchand et al. (2001) showed that efficient actin nucleation requires both recruitment of an actin monomer to the ARP2/3 complex and a subsequent activation step. The initial steps in this pathway involve binding by the WA domain of WASP/SCAR (605035) proteins, which consists of a WH2 motif (W) that binds to the actin monomers and an acidic tail (A) that binds to the ARP2/3 complex. Actin filaments seem to stimulate nucleation by enhancing binding of WA to the ARP2/3 complex and favoring the formation of a productive nucleus. </p><p>WAS is caused by a mutation in the WAS protein that results in defective actin polymerization. Although the function of many hematopoietic cells requires WAS protein, the specific expression and function of this molecule in natural killer (NK) cells was unknown. Orange et al. (2002) reported that WAS patients had increased percentages of peripheral blood NK cells and that fresh enriched NK cells from 2 patients with a WAS protein mutation had defective cytolytic function. In normal NK cells, WAS protein was expressed and localized to the activating immunologic synapse with filamentous actin (F-actin). Perforin-1 (170280) also localized to the NK cell-activating immunologic synapse, but at a lesser frequency than F-actin and WAS protein. The accumulation of F-actin and WAS protein at the activating immunologic synapse was decreased significantly in NK cells that had been treated with the inhibitor of actin polymerization, cytochalasin D. NK cells from WAS patients lacked expression of WAS protein and accumulated F-actin at the activating immunologic synapse infrequently. Thus, WAS protein has an important function in NK cells. In patients with WAS protein mutations, the resulting NK cell defects are likely to contribute to their disease. </p><p>Missense mutations that cause WAS map primarily to the enabled (609061)/VASP (601703) homology-1 (EVH1) domain of WASP. This domain, which is also present in N-WASP (WASL; 605056), has been implicated in both peptide and phospholipid binding. Volkman et al. (2002) showed that the N-WASP EVH1 domain does not bind phosphatidylinositol 4,5-bisphosphate, but it does specifically bind a 25-residue motif from WASP-interacting protein (WIP; 602357). The nuclear magnetic resonance (NMR) structure of the complex revealed a novel recognition mechanism in which the WIP ligand, which is far longer than canonical EVH1 ligands, wraps around the domain, contacting a narrow but extended surface. The authors concluded that this recognition mechanism may provide a basis for understanding the effects of mutations that cause WAS. </p><p>Sasahara et al. (2002) showed that the adaptor protein CRKL (602007) binds directly to WIP and that, following T-cell receptor ligation, a CRKL-WIP-WASP complex is recruited by ZAP70 (176947) to lipid rafts and immunologic synapses. </p><p>Using mass spectrometric analysis, Scott et al. (2002) identified 25 potential binding partners in a human monocyte cell line for the SH3 domain of HCK (142370). Analysis with purified proteins and in intact cells confirmed the interactions with WIP, WASP, and ELMO1 (606420). Scott et al. (2002) concluded that WIP, WASP, and ELMO1 may be activators or effectors of HCK. </p><p><strong><em>X-Inactivation Status</em></strong></p><p>
|
|
Wengler et al. (1995) stated that obligate female carriers of the gene for X-linked agammaglobulinemia (300755) show nonrandom X-chromosome inactivation only in B lymphocytes, and obligate female carriers of the gene for X-linked severe combined immunodeficiency (XSCID) show nonrandom X-chromosome inactivation in both T and B lymphocytes, as well as natural killer cells. However, all formed elements of the blood appear to be affected, as a rule, in obligate carriers of WAS, as judged by the criteria of nonrandom X-chromosome inactivation and segregation of G6PD alleles in informative females. Wengler et al. (1995) demonstrated that CD34+ hematopoietic progenitor cells collected from obligate carriers of WAS by apheresis showed nonrandom inactivation. They used PCR analysis of a polymorphic VNTR within the X-linked androgen receptor gene (313700) to demonstrate nonrandom inactivation which clearly must occur early during hematopoietic differentiation. </p><p>Parolini et al. (1998) reported X-linked WAS in an 8-year-old girl. She had a sporadic mutation, glu133 to lys, on the paternally derived X chromosome, but had nonrandom X inactivation of the maternal X chromosome in both blood and buccal mucosa. Her mother and maternal grandmother also had nonrandom X inactivation, which suggested to the authors the possibility of a defect in XIST (314670) or some other gene involved in the X-inactivation process. Puck and Willard (1998) commented on the subject of X inactivation in females with X-linked disease in reference to the paper by Parolini et al. (1998). </p><p><strong><em>Reviews</em></strong></p><p>
|
|
Snapper and Rosen (1999) reviewed the roles of WASP in signaling and cytoskeletal organization. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Cheng et al. (2008) showed that the E. coli EspFU protein binds to the autoinhibitory GTPase binding domain in WASP proteins and displaces it from the activity-bearing VCA domain (for verprolin homology, central hydrophobic, and acidic regions). This interaction potentially activates WASP and neural WASP in vitro and induces localized actin assembly in cells. In the solution structure of the GBD-EspFU complex, EspFU forms an amphipathic helix that binds the GBD, mimicking interactions of the VCA domain in autoinhibited WASP. Thus, EspFU activates WASP by competing directly for the VCA binding site on the GBD. This mechanism is distinct from that used by the eukaryotic activators Cdc42 (116952) and SH2 domains, which globally destabilize the GBD fold to release the VCA. Cheng et al. (2008) suggested that such diversity of mechanisms in WASP proteins is distinct from other multimodular systems, and may result from the intrinsically unstructured nature of the isolated GBD and VCA elements. The structural incompatibility of the GBD complexes with EspFU and Cdc42/SH2, plus high-affinity EspFU binding, enable enterohemorrhagic E. coli to hijack the eukaryotic cytoskeletal machinery effectively. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Mutations in the WAS gene have been found in patients with Wiskott-Aldrich syndrome, X-linked thrombocytopenia (313900), and X-linked severe congenital neutropenia (SCNX; 300299).</p><p>Derry et al. (1994) found that the WAS gene was not expressed in 2 unrelated patients with Wiskott-Aldrich syndrome, 1 of whom had a single base deletion that produced a frameshift and premature termination of translation (300392.0001). Two additional patients were identified with point mutations that changed the same arginine residue to either a histidine or a leucine (300392.0002-300392.0003). </p><p>In patients with Wiskott-Aldrich syndrome, Kwan et al. (1995) identified 11 additional mutations in the WAS gene that involved single base changes, small deletions, and an insertion. They tabulated 12 mutations in all, located in 6 different exons. </p><p>Kolluri et al. (1995) used PCR-SSCP analysis to screen for WAS gene mutations in 19 unrelated boys with the diagnosis of classic or attenuated WAS or isolated thrombocytopenia. All 19 patients had WAS mutations, each of which localized to the initial 3 or terminal 3 exons of the gene, and most of which were unique in each case. However, the arg86-to-his mutation (300392.0003) was found in 1 boy with severe WAS, and an arg86-to-cys mutation was found in 2 boys with severe WAS and 1 boy presenting with thrombocytopenia alone. While the 3 mutations found in isolated thrombocytopenia patients left the reading frame intact, about one-half of the gene alterations detected in both severe and attenuated WAS patients resulted in a frameshift and premature translation termination. </p><p>Schindelhauer et al. (1996) found 7 novel and 10 known mutations in the course of mutation analysis in 19 families of German, Swiss, and Turkish descent who presented with WAS and with X-linked thrombocytopenia. They noted a striking clustering of missense mutations in the first 4 exons that contrasted with a random distribution of nonsense mutations. More than 85% of all known missense mutations were located in the amino-terminal stretch of the WAS gene product; this region contained a mutation hotspot at codon 86 (see 300392.0002 and 300392.0003); R86C, R86H, and R86P were observed in this study and R86H was found in 2 unrelated families. </p><p>Sequence studies in a WAS patient reported by Stewart et al. (1996) showed a C-to-G transversion at nucleotide position 155 which caused an arginine-to-glycine substitution at codon 41; in a second patient, a C insertion after nucleotide 1016 produced a frameshift resulting in amino acid substitutions at codons 328, 329, 331, and 332. Deletion of a G just after nucleotide 1029 returned the reading frame to normal. </p><p>In a study of 16 WAS patients and 4 X-linked thrombocytopenia patients, Thompson et al. (1999) identified 14 distinct mutations, including 7 novel gene defects. Fillat et al. (2001) screened for mutations in the WASP gene using single-strand conformation analysis (SSCA) and sequencing in 14 unrelated Spanish families with 19 affected individuals presenting variable WAS phenotypes. Thirteen mutations (including 9 missense mutations) were identified. Missense mutations were preferentially located in the N-terminal part of the protein (exons 2 and 4), whereas nonsense and frameshift mutations were located in the C-terminal region (exons 10 and 11). </p><p>Villa et al. (1995) presented proof that mutations in the WAS gene can result in X-linked thrombocytopenia characterized by thrombocytopenia with small-sized platelets as an isolated finding. Why some mutations impair only the megakaryocytic lineage and have no apparent effect on the lymphoid lineage was unclear. De Saint Basile et al. (1996) also found single point mutations in exon 2 of the WAS gene in 2 unrelated families with a history of isolated X-linked thrombocytopenia. </p><p>Devriendt et al. (2001) demonstrated that a constitutively activating mutation in WASP can cause X-linked severe congenital neutropenia; see 300392.0012. </p><p>Dobbs et al. (2007) identified 2 different but contiguous single basepair deletions in maternal cousins with WAS (300392.0022 and 300392.0023, respectively). The maternal grandmother was found to be a mosaic for the deletions, both of which occurred on the haplotype from the unaffected maternal great-grandfather, consistent with a bichromatid mutation in a male gamete. </p><p>Ancliff et al. (2006) analyzed the WAS gene in 14 boys with severe congenital neutropenia who were negative for mutation in the ELA2 (ELANE; 130130) gene, 8 with classic SCN and 6 with evidence of myelodysplasia and/or immunologic abnormalities in addition to neutropenia, and identified 2 different mutations in 2 probands (S272P, 300392.0024; I294T,300392.0025, respectively). </p><p>Beel et al. (2008) analyzed the WAS gene in 60 members of a large Irish kindred segregating X-linked congenital neutropenia, originally reported by Cryan et al. (1988), and identified the I294T mutation in 10 affected males and 8 female carriers. </p><p>Humblet-Baron et al. (2007) identified a WAS patient with a history of recurrent autoimmune hemolytic anemia who had a spontaneous revertant mutation in WASP. Previous studies had identified a single-nucleotide deletion in WASP that led to a frameshift, a premature stop codon, and absence of WASP expression. Repeated genetic studies using peripheral blood lymphocytes and a newly derived T-cell line revealed a single-nucleotide insertion at the same genomic site that restored the normal ORF and WASP expression. The reversion was associated with an increase in the relative percentage of WASP-positive/CD4 (186940)-positive/FOXP3 (300292)-positive regulatory T cells (Tregs), as well as clinical improvement manifested by stabilization of red blood cell count and reduction in steroid therapy. Humblet-Baron et al. (2007) concluded that wildtype Tregs expanded in this patient following reversion of a pathogenic WASP mutation, indicating that altered Treg fitness likely explains the autoimmune features in human WAS. </p><p><strong><em>Revertant Mosaicism</em></strong></p><p>
|
|
Wada et al. (2001) provided evidence that in vivo reversion had occurred in the WAS gene in a patient with Wiskott-Aldrich syndrome, resulting in somatic mosaicism. The mutation was a 6-bp insertion (ACGAGG; 300392.0008) which abrogated expression of the WAS protein. Most of the patient's T lymphocytes expressed nearly normal levels of WAS protein. These lymphocytes were found to lack the deleterious mutation and showed a selective growth advantage in vivo. Analysis of the sequence surrounding the mutation site showed that the 6-bp insertion followed a tandem repeat of the same 6 nucleotides. These findings strongly suggested that DNA polymerase slippage was the cause of the original germline insertion mutation in this family and that the same mechanism was responsible for its deletion in one of the proband's T-cell progenitors, thus leading to reversion mosaicism. </p><p>Wada et al. (2004) described 2 additional patients from the same family of the man with revertant T-cell lymphocytes reported by Wada et al. (2001). Somatic mosaicism was demonstrated in leukocytes from the first patient that were cryopreserved when he was 22 years old, 11 years before his death from kidney failure. The second patient, 16 years old at the time of report, had a moderate clinical phenotype and developed revertant cells after the age of 14 years. T lymphocytes showed selective in vivo advantage. These results supported DNA polymerase slippage as a common underlying mechanism and indicated that T-cell mosaicism may have different clinical effects in WAS. Wada et al. (2004) stated that sibs with revertant mosaicism had previously been reported (Wada et al., 2003; Waisfisz et al., 1999), but 3 patients with revertant disease in a single kindred was unprecedented. </p><p><strong><em>Somatic Mosaicism with Second-Site Mutations</em></strong></p><p>
|
|
Boztug et al. (2008) reported 2 Ukrainian brothers, aged 3 and 4 years, respectively, with WAS due to somatic mosaicism for a truncation mutation and multiple different second-site mutations. Flow cytometric analysis of peripheral blood cells showed that each patient had WAS-negative cells resulting from the truncation mutation and a subset of WAS-positive cells that expressed second-site missense WAS mutations. The second-site mutations resulted in the production of altered, but possibly functional, protein. All second-site mutations in both patients occurred in the same nucleotide triplet in which the truncation mutation occurred. Over time, both boys had a decrease in bleeding diathesis and eczema, and normalization of platelet counts. Boztug et al. (2008) suggested that the second-site mutations may confer a proliferative advantage to the affected cells in these patients. </p><p>Du et al. (2006) described somatic mosaicism in a 15-year-old WAS patient due to a second-site mutation in the initiation codon. The patient had a germline single-base deletion (11delG; 300392.0019) in the WASP gene, which resulted in a frameshift and abrogated protein expression. Subsequently, a fraction of T and natural killer (NK) cells expressed a smaller WASP, which bound to its cellular partner WASP-interacting protein (WASPIP; 602357). The T and NK cells were found to have an additional mutation in the initiation codon (1A-T; 300392.0020). The results strongly suggested that the smaller WASP was translated from the second ATG downstream of the original mutation, and not only T cells but also NK cells carrying the second mutation acquired a growth advantage over WASP-negative counterparts. This appeared to be the first report describing somatic mosaicism due to a second-site mutation in the initiation codon in an inherited disorder. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Derry et al. (1995) described the spectrum of novel mutations in 12 additional unrelated families: missense, nonsense, and frameshift mutations involving 8 of the 12 exons of the gene. Two mutations creating premature termination codons were associated with lack of detectable mRNA on Northern blots. Four amino acid substitutions were found in patients with congenital thrombocytopenia and no clinically evident immune defect. A T-cell line from a WAS patient contained 2 independent DNA alterations, a constitutional frameshift mutation also present in peripheral blood lymphocytes from the patient, and a compensatory splice site mutation unique to the cell line. Although RNA from untransformed cells was not available for analysis, Derry et al. (1995) proposed that the splice site mutation was introduced into the T cell during transformation with HTLV-1 and was then selected for during expansion of the culture. The selection hypothesis implies that a mutant protein lacking the 14 amino acids of exon 8 was produced and conveyed a growth advantage to the cells that carried it. In support of this idea was the observation of nonrandom X-inactivation of circulating lymphocytes in female carriers for WAS, due to selection for cells with the normal X chromosome active. Sites in the first 2 exons of the WAS gene appear to be hotspots for mutation; 20 of 31 unrelated families studied by Kolluri et al. (1995) and Derry et al. (1995) had mutations in exon 1 or exon 2. </p><p>Wengler et al. (1995) identified 15 novel mutations in the WAS gene in patients with full-blown Wiskott-Aldrich syndrome. These mutations involved single basepair changes, or small insertions or deletions, all of which resulted in premature stop codon, frameshift with secondary premature stop codon, or splice site defect. Zhu et al. (1995) likewise identified 12 unique mutations distributed throughout the WAS gene. Patients with classic WAS had 'more complex' mutations, resulting in termination codons, frameshifts, and early termination. By contrast, 4 unrelated patients with the X-linked thrombocytopenia phenotype had missense mutations affecting exon 2 (in 3) and a splice site mutation affecting exon 9 (in 1). </p><p>Schindelhauer et al. (1996) found no genotype/phenotype correlation emerge after a comparison of the identified mutations with the resulting clinical picture for a classic WAS phenotype. A mild course, reminiscent of X-linked thrombocytopenia, or an attenuated phenotype was more often associated with missense than with the other types of mutations. </p><p>Greer et al. (1996) examined the genotypes and phenotypes of 24 patients with WAS and compared them with other known mutations of the WASP gene. They demonstrated clustering of WASP mutations within the 4 most N-terminal exons of the gene and identified arg86 as the most prominent hotspot for WASP mutations. They noted the prominence of missense mutations among patients with milder forms of WAS, while noting that missense mutations also comprise a substantial portion of mutations in patients with severe forms of the disease. Greer et al. (1996) concluded that phenotypes and genotypes of WAS are not well correlated; phenotypic outcome cannot be reliably predicted on the basis of WASP genotype. </p><p>Lemahieu et al. (1999) identified 17 WASP gene mutations, 12 of which were novel. All missense mutations were located in exons 1 to 4. Most of the nonsense, frameshift, and splice site mutations were found in exons 6 to 11. Mutations that alter splice sites led to the synthesis of several types of mRNAs, a fraction of which represented the normally spliced product. The presence of normally spliced transcripts was correlated with a milder phenotype. When one such case was studied by Western blot analysis, reduced amounts of normal-sized WASP were present. In other cases as well, a correlation was found between the amount of normal or mutant WASP present and the phenotypes of the affected individuals. No protein was detected in 2 individuals with severe Wiskott-Aldrich syndrome. Reduced levels of a normal-sized WASP with a missense mutation were seen in 2 individuals with X-linked thrombocytopenia. Lemahieu et al. (1999) concluded that mutation analysis at the DNA level is not sufficient for predicting clinical course, and that studies at the transcript and protein levels are needed for a better assessment. </p><p>Imai et al. (2004) characterized WASP gene mutations in 50 Japanese patients and analyzed the clinical phenotype and course of each. All patients with missense mutations were WASP-positive, i.e., showed presence of the WASP protein; in contrast, patients with nonsense mutations, large deletions, small deletions, and small insertions were WASP-negative. Patients with splice anomalies were either WASP-positive or WASP-negative. The clinical phenotype of each patient correlated with the presence or absence of WASP. Lack of WASP expression was associated with susceptibility to bacterial, viral, fungal, and Pneumocystis carinii infections and with severe eczema, intestinal hemorrhage, death from intracranial bleeding, and malignancies. Rates for overall survival or survival without intracranial hemorrhage or other serious complications were significantly lower in WASP-negative patients. </p><p>Vallee et al. (2024) evaluated 577 individuals with Wiskott-Aldrich syndrome from 63 centers in 26 countries born between 1932 and 2014. The median age at diagnosis was 1.5 years (range, 0-68). Of these patients, 464 (80.4%) were alive at last follow-up, and the median age at last follow-up was 8.9 years (range, 0.3-71.1). This resulted in a total of 6,118 reported patient-years. Overall survival of the cohort, censored at hematopoietic stem cell transplant or gene therapy, was 82% (95% confidence interval (CI) 78-87) at age 15 years and 70% (95% CI 61-80) at 30 years. Vallee et al. (2024) found that those with a missense variant in exon 1 or 2 or the intronic hotspot variant c.559+5G-A (300392.0016) (called class I variants) had a better outcome than those with any other variant (class II variants). Individuals with class I variants had a 15-year odds of survival of 93% (95% CI 89-98) and a 30-year odds of survival of 91% (95% CI 86-97), compared with 71% (95% CI 62-81) and 48% (95% CI 34-68) in patients with class II variants. The cumulative incidence rates of disease-related complications such as severe bleeding (p = 0.007), life-threatening infection (p less than 0.0001), and autoimmunity (p = 0.004) occurred significantly later in patients with a class I variant. The cumulative incidence of malignancy (p = 0.6) was not different between classes I and II. Vallee et al. (2024) concluded that their study quantified the risk for specific disease-related complications and that the class of variant is a biomarker to predict the outcome in patients with WAS. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Derry et al. (1995) stated that Wasp may be a candidate for involvement in 'scurfy,' a T cell-mediated fatal lymphoreticular disease of mice that had previously been proposed as a mouse homolog of Wiskott-Aldrich syndrome (Lyon et al., 1990). Northern analysis of sf tissue samples indicated the presence of Wasp mRNA in liver and skin, presumably as a consequence of lymphocyte infiltration, but no abnormalities in the amount or size of mRNA were identified. </p><p>Snapper et al. (1998) found that Wasp -/- mice had normal lymphocyte development and Ig levels and responded well to T-dependent and -independent antigens. However, they had decreased peripheral blood lymphocyte and platelet numbers and developed chronic colitis. Responses to anti-Cd3e (186830) stimulation were impaired in Wasp -/- T cells, whereas Wasp -/- B cells responded normally to anti-Ig. </p><p>Humblet-Baron et al. (2007) found that Wasp -/- mice developed early-onset, high-titer autoantibodies. Wasp -/- Tregs failed to compete effectively in vivo and were unable to maintain immunologic tolerance in Treg -/- mice. Flow cytometric analysis demonstrated reduced expression of adhesion molecules and chemokine receptors necessary for nonlymphoid tissue entry in Wasp -/- Tregs, suggesting a defect in peripheral Treg activation. Humblet-Baron et al. (2007) concluded that altered fitness of Tregs may explain the autoimmune features of WAS. </p><p>Marangoni et al. (2007) found that Wasp -/- natural Tregs (nTregs) engrafted poorly in immunized mice and failed to proliferate or produce Tgfb (190180). Wasp -/- nTregs also showed reduced suppressor cell function against either wildtype or Wasp -/- effector T cells. Human nTregs from WAS patients showed a similar phenotype. Marangoni et al. (2007) proposed that WASP plays an important role in the activation and suppressor functions of nTregs and that dysfunction or incorrect localization of nTregs may contribute to autoimmunity in WAS patients. </p><p>Maillard et al. (2007) demonstrated that Wasp -/- mice have decreased numbers of nTregs in thymus and peripheral organs. Wasp -/- nTregs failed to protect against development of colitis in vivo and failed to home to mesenteric mucosa and peripheral sites upon adoptive transfer into wildtype recipient mice. Wasp -/- nTregs had reduced suppressor function in vitro, which could be restored by preincubation with Il2 (147680) and antigen receptor activation, and they were defective in Il10 (124092) secretion. Maillard et al. (2007) concluded that WASP is critical for nTreg function and that nTreg dysfunction is involved in autoimmunity associated with WASP deficiency. </p><p>Using 2 different gene-targeting approaches, Cotta-de-Almeida et al. (2007) generated mouse T lymphocytes lacking both Wasp and N-Wasp. These double-knockout T cells were indistinguishable from wildtype T cells, but T-cell development was markedly altered in double-knockout mice. Flow cytometric analysis demonstrated reduced thymocyte and peripheral T-cell numbers in double-knockout mice. Cotta-de-Almeida et al. (2007) found that the combined activity of Wasp and N-Wasp was important for transition from Cd4/Cd8 double-negative thymocytes to Cd4/Cd8 double-positive thymocytes. In addition, double-knockout mice exhibited decreased migration of single-positive T cells from the thymus. Cotta-de-Almeida et al. (2007) concluded that WASP has a unique role in peripheral T-cell function, but T-cell development depends on the combined activity of WASP and N-WASP. </p><p>Westerberg et al. (2010) created mice with mutations in the mouse Wasp gene corresponding to the human leu270-to-pro (L270P; 300392.0012) and ile294-to-thr (I294T; 300392.0025) mutations, which cause X-linked neutropenia (SCNX; 300299). These mutations interfered with normal lymphocyte activation by inducing a marked increase in polymerized actin, decreased cell spreading, and increased apoptosis associated with increased genomic instability. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>25 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, 1-BP DEL, 211T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2147262829,
|
|
|
|
|
|
|
|
ClinVar: RCV000011862
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Wiskott-Aldrich syndrome (WAS; 301000) who on Northern blot analysis lacked a visible transcript for WAS, Derry et al. (1994) found deletion of a thymine at nucleotide position 211. The change interrupted the predicted open reading frame and led to a termination signal 16 codons downstream. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, ARG86LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs132630268,
|
|
|
|
|
|
|
|
ClinVar: RCV000011863
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Wiskott-Aldrich syndrome (WAS; 301000), Derry et al. (1994) found a G-to-T transversion that changed codon 86 from an arginine to a leucine. The mutation was identified in the mother and maternal grandmother. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, ARG86HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs132630268,
|
|
|
|
|
|
|
|
ClinVar: RCV000011864, RCV000414284, RCV000633305
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Wiskott-Aldrich syndrome (WAS; 301000), unrelated to the patient with the arg86-to-leu mutation (300392.0002), Derry et al. (1994) identified a G-to-A transition at nucleotide 291 changing the same arginine to a histidine. The patient's mother and maternal grandmother were heterozygous for the mutant allele. In one instance, the normal codon CGC was changed to CTC (leu); in the other instance, it was changed to CAC (his). </p><p>Schindelhauer et al. (1996) found extremely variable expression of a disease in a large Swiss family with the R86H mutation of 5 affected males. One died in infancy from infections and 2 were diagnosed as having the classic WAS phenotype. In contrast, 2 brothers had a mild phenotype with survival into adulthood and had children of their own. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 THROMBOCYTOPENIA, X-LINKED, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, ALA56VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs132630269,
|
|
|
|
|
|
|
|
ClinVar: RCV000011865, RCV001563489, RCV002243636, RCV003764557
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old boy with thrombocytopenia with small-sized platelets (THC1; 313900) diagnosed at 3 months of age, Villa et al. (1995) found a C-to-T transition in exon 2 at nucleotide 201, which was predicted to cause substitution of valine for alanine at codon 56. The patient had never shown eczema or increased susceptibility to infection. The same mutation was found in 1 allele in the mother. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 THROMBOCYTOPENIA, X-LINKED, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, ALA236GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs132630270,
|
|
|
|
|
|
|
|
ClinVar: RCV000011866
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old boy with a negative family history and thrombocytopenia with small-sized platelets (THC1; 313900) who presented with petechiae at the age of 5 months, Villa et al. (1995) found a C-to-G transversion at nucleotide 741 in exon 7, predicted to lead to substitution of glutamic acid for alanine at codon 236. The mother showed the same mutation in 1 allele. The patient had had mild and transient eczema at 10 months of age but had never shown susceptibility to infections. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 THROMBOCYTOPENIA, X-LINKED, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, 1-BP INS, 512C
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011867
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 9-year-old boy who presented with petechiae at the age of 6 months and was found to have thrombocytopenia with small-sized platelets (THC1; 313900), Villa et al. (1995) found a C insertion in a stretch of 5 cytosines between nucleotides 512 and 516 (in exon 1). The insertion caused a shift in the reading frame after codon 160, leading to a premature termination 8 codons downstream at nucleotides 535-537. The same mutation was detected in 1 allele in the mother. The patient had never developed eczema and showed no unusual susceptibility to infections. A younger brother was also affected. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, ARG34TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs132630271,
|
|
|
|
|
|
gnomAD: rs132630271,
|
|
|
|
|
|
ClinVar: RCV000011868, RCV003764558
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>One of 11 new mutations identified by Kwan et al. (1995) in patients with Wiskott-Aldrich syndrome (WAS; 301000) was a CGA-to-TGA transition in exon 1, resulting in an arg34-to-ter conversion. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, 6-BP INS, NT434
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776743,
|
|
|
|
|
|
|
|
ClinVar: RCV000011870
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>One of 11 mutations in patients with Wiskott-Aldrich syndrome (WAS; 301000) identified by Kwan et al. (1995) was a 6-bp insertion (ACGAGG) at nucleotide 434 resulting in the introduction of 2 additional amino acids, asp and glu. The mutation occurred in exon 4. </p><p>Wada et al. (2001) described a case of somatic mosaicism for this mutation caused by in vivo reversion. The patient came from a kindred in which 6 males in 4 sibships connected by carrier females had Wiskott-Aldrich syndrome (301000). At the age of 10 months, the proband had encephalitis, and between the ages of 2 and 5 years, he had recurrent bruising, eczema, and recurrent otitis media. At age 5, his platelet count was found to be low. Elective splenectomy corrected the platelet number and size. Shortly after splenectomy, he suffered from pneumococcal meningitis. Frequent upper respiratory and/or ear infections and continued eczema occurred until the age of 12 years when the patient was hospitalized for vasculitic rash, thrombocytopenia, and an illness resembling rheumatoid arthritis with concurrent dysgammaglobulinemia and nephritis. The same year, he developed pneumococcal meningitis and sepsis, which were successfully treated. One month later, another episode of pneumococcal meningitis occurred. At age 16, he developed right mastoiditis. From his 20s to the time of report at age 43, the patient had been relatively well, with complaints of sinusitis responding to antibiotic treatment. A maternal uncle developed petechiae early after birth and died at 6 months of age. His brother had a severe WAS phenotype, including thrombocytopenia, infections, arthritis, and vasculitis, and died of renal failure at the age of 33 years. Two maternal cousins also had severe WAS symptoms; one died from pulmonary hemorrhage at age 2.5 years and the other from lymphoma at age 18 years. Wada et al. (2001) identified the ACGAGG insertion in the WAS gene of the proband. They documented somatic mosaicism in the patient, most of whose T lymphocytes expressed nearly normal levels of WAS protein and were found to lack the deleterious mutation. The sequence surrounding the mutation site showed that the 6-bp insertion followed a tandem repeat of the same 6 nucleotides. These findings strongly suggested that DNA polymerase slippage was the cause of the original germline insertion mutation in this family and that the same mechanism was responsible for its deletion in one of the T-cell progenitors in the proband, thus leading to reversion mosaicism and clinical cure. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 WISKOTT-ALDRICH SYNDROME, ATTENUATED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, SER82PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs132630272,
|
|
|
|
|
|
|
|
ClinVar: RCV000011871, RCV001509116
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In addition to classic Wiskott-Aldrich syndrome on the one hand and isolated thrombocytopenia on the other, some patients with mutations in the WAS gene have atypical or attenuated WAS (301000). In contrast to classic WAS patients, the boys manifested only a mild to moderately severe hemorrhagic diathesis during childhood, had mild or no eczema, and lacked a history of severe recurrent infections. As in classic WAS patients, the boys with attenuated WAS showed variable expression of immune abnormalities and their T cells showed lack of proliferative responses to the periodate mitogen, a finding apparently restricted to, and diagnostic of, WAS (Siminovitch et al., 1995). One of the attenuated or atypical cases of WAS reported by Kolluri et al. (1995) was a 27-year-old man who had easy bruising, epistaxis since infancy, mild eczema, and recurrent pneumonia. Renal failure from the age of 13 years required dialysis. A splenectomy was performed at age 23 years following intracranial hemorrhage. The patient was found to carry a T-to-C transition of nucleotide 278, resulting in a ser82-to-pro substitution in exon 2. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 THROMBOCYTOPENIA, X-LINKED, 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, THR45MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs132630273,
|
|
|
|
|
|
|
|
ClinVar: RCV000011872, RCV000851684, RCV001037597, RCV001172206, RCV004748516, RCV004760326
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>De Saint Basile et al. (1996) described a new mutation in a patient from a family with X-linked thrombocytopenia (THC1; 313900). Exon 2 products showed abnormal migration by single-strand conformational polymorphism analysis. A 168C-T transition produced a thr45-to-met missense mutation with no change in charge. </p><p>Ho et al. (2001) found the thr45-to-met mutation in affected members of a large Syrian-Lebanese family with X-linked thrombocytopenia. Five family members had undergone splenectomy with rapid and sustained normalization of their platelet numbers. Ho et al. (2001) pointed out that exon 2 is the most common site for mutations associated with XLT and mild forms of WAS, and the 168C-T transition is the most frequent. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, 1-BP DEL, 1127G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776744,
|
|
|
|
|
|
|
|
ClinVar: RCV000011873
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Wiskott-Aldrich syndrome (WAS; 301000), Ariga et al. (1998) observed 2 mutations in exon 10 of the WASP gene. One mutation was a 1-bp insertion (A) at nucleotide 1099 or 1100. The other was a 1-base deletion (G) from 5 consecutive Gs at nucleotides 1127 to 1131. On further study it was found that some clones contained only the insertion mutation and the patient's mother and sister, who were both carriers, had only the deletion mutation. It was suggested that the insertion mutation occurred somatically in a hematologic progenitor and was potentially capable of correcting the inherited defect. The proband died at the age of 4 years from intracranial hemorrhage; 2 older brothers who also had Wiskott-Aldrich syndrome died at the ages of 10 months and 47 months. It was uncertain whether the proband's disorder was milder as a result of the second mutation. Spontaneous in vivo reversion to normal of an inherited mutation was reported in a patient with adenosine deaminase deficiency (102700.0026) by Hirschhorn et al. (1996). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 NEUTROPENIA, SEVERE CONGENITAL, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, LEU270PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs132630274,
|
|
|
|
|
|
|
|
ClinVar: RCV000011874, RCV001291553, RCV001851800
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family in which males showed severe congenital neutropenia in an X-linked recessive pedigree pattern (SCNX; 300299) with affected males in 3 sibships in 3 generations, Devriendt et al. (2001) demonstrated a constitutively activating mutation in WASP: an 843T-C transition causing a leu270-to-pro (L270P) mutation in the WAS gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 THROMBOCYTOPENIA, X-LINKED, INTERMITTENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, PRO58ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs132630275,
|
|
|
|
|
|
|
|
ClinVar: RCV000011875
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Notarangelo et al. (2002) described 2 families in which affected males had a history of intermittent thrombocytopenia (THC1; 313900) with consistently reduced platelet volume, in the absence of other major clinical features, and carried missense mutations of the WASP gene that allowed substantial protein expression. This observation broadened the spectrum of clinical phenotypes associated with WASP gene defects, and indicated the need for molecular analysis in males with reduced platelet volume, regardless of the platelet number. In 1 family reported by Notarangelo et al. (2002), the index case was that of a 7-year-old boy in whom petechiae developed at 1 month of age. He had mild and transient antecubital eczema in infancy. A diagnosis of idiopathic thrombocytopenia was made at the age of 2 years. He continued to have intermittent petechiae and occasional epistaxis associated with variability in the platelet count, but he had consistently low mean platelet volume. His 4-year-old brother and a 39-year-old maternal uncle also had histories of intermittent petechiae, without other symptoms. In this family a 207C-G nucleotide substitution was found in exon 2 of the WAS gene in all 3 affected males, resulting in a pro58-to-arg (P58R) amino acid change. Heterozygosity for this mutation was detected in the mother of the 2 boys. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 THROMBOCYTOPENIA, X-LINKED, INTERMITTENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, ILE481ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs132630276,
|
|
|
|
|
|
|
|
ClinVar: RCV000011876
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a second family with intermittent thrombocytopenia (WAS; 313900) reported by Notarangelo et al. (2002), a single male was affected, a 7-year-old boy who at the age of 3 years had petechiae and bruises. Clinical history was unremarkable for eczema and infection, and immunoglobulins were normal. Mutation analysis revealed a 1476T-A point mutation in exon 11 of the WAS gene, resulting in an ile481-to-asn (I481N) amino acid substitution. The mother was found to be a carrier of this mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, 15,800-BP DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011877
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Lutskiy et al. (2002) described a patient with Wiskott-Aldrich syndrome (WAS; 301000) with a large deletion in the Xp11.23 region. The deletion, which totaled 15.8 kb, began downstream of DXS1696 and encompassed 13 kb upstream of WASP and included the distal and proximal promoters and exons 1 through 6. The upstream breakpoint was localized in an Alu element. A 26-bp recombinogenic element was located downstream of the 5-prime breakpoint. A 16-bp sequence just upstream of the 5-prime breakpoint shared close homology with the sequence that spanned the 3-prime breakpoint in intron 6. A heptanucleotide of unknown origin, CAGGGGG, linked the 5-prime and 3-prime breakpoints. Lutskiy et al. (2002) stated that this was the largest deletion identified in a Wiskott-Aldrich syndrome patient. The diagnosis had been made at the age of 3 months when he presented with thrombocytopenia, small platelets, severe eczema, bloody diarrhea, and recurrent otitis media. He received regular immunoglobulin transfusions; at age 2 years, splenectomy was performed and, at age 4, he received a bone marrow transplant from an HLA-matched unrelated donor. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
THROMBOCYTOPENIA, X-LINKED, 1, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, IVS6DS, G-A, +5
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs886039451,
|
|
|
|
|
|
|
|
ClinVar: RCV000413138, RCV001390443, RCV001810445, RCV001810446
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Wiskott-Aldrich Syndrome</em></strong>
|
|
</p>
|
|
|
|
<p>In a patient with Wiskott-Aldrich syndrome (301000), Kwan et al. (1995) identified a G-to-A transition at position +5 of intron 6 of the WAS gene. </p>
|
|
|
|
<div class="mim-changed mim-change"><p>Using RT-PCR, Zhu et al. (1997) found that the IVS6+5G-A variant resulted in 30% wildtype transcripts, and protein was present on Western blot at 3.5% of wildtype levels. </p></div>
|
|
|
|
<div class="mim-changed mim-change"><p>Jin et al. (2004) identified this variant as a mutational hotspot, present in in 6/227 (2.6%) of the WAS families they studied. </p></div>
|
|
|
|
<div class="mim-changed mim-change"><p>Vallee et al. (2024) catagorized the c.559+5G-A mutation as a class I variant, correlated with a milder phenotype and better outcome. It was present in 22/525 (4.2%) of WAS patients with definitive genetic information. </p></div>
|
|
|
|
<p />
|
|
<p><strong><em>Thrombocytopenia 1</em></strong>
|
|
</p>
|
|
|
|
<p>Inoue et al. (2002) reported what they believed to be the first confirmed instance of X-linked thrombocytopenia (THC1; 313900) in a female. She had the IVS6+5G-A mutation in the WAS gene. Her lymphocytes showed a random pattern of X-chromosome inactivation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, IVS6AS, G-A, -1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1602178087,
|
|
|
|
|
|
|
|
ClinVar: RCV000011880
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Kwan et al. (1995) described a G-to-A transition at position -1 of intron 6 of the WAS gene in a patient with Wiskott-Aldrich syndrome (WAS; 301000). Lutskiy et al. (2002) studied a 14-month-old girl, a cousin of that patient, who had Wiskott-Aldrich syndrome presenting with thrombocytopenia, small platelets, and immunologic dysfunction. Sequencing of the WAS gene showed that the patient was heterozygous for the splice site mutation previously found in her maternal cousin. Levels of WASP in blood mononuclear cells were 60% of normal. X chromosome inactivation in the patient's blood cells was random, demonstrating that both maternal and paternal active X chromosomes were present. These findings indicated that this patient had a defect in the mechanisms that, in disease-free WAS carriers, lead to preferential survival/proliferation of cells bearing the active wildtype X chromosome. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, IVS6DS, T-G, +2
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1602177733,
|
|
|
|
|
|
|
|
ClinVar: RCV000011881
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Andreu et al. (2003) reported an IVS6+2T-G splice site mutation in the WAS gene in a boy with Wiskott-Aldrich syndrome (WAS; 301000). As a consequence of the disruption of the normal splicing process, an abnormally long transcript of 38 nucleotides was generated. Such missplicing was probably due to the activation of a cryptic splice donor site located 38 nucleotides downstream of exon 6. The translation of such aberrant mRNA was predicted to produce a truncated protein with a premature stop at codon 190. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, 1-BP DEL, 11G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776745,
|
|
|
|
|
|
gnomAD: rs587776745,
|
|
|
|
|
|
ClinVar: RCV000011882, RCV001225126
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Du et al. (2006) described somatic mosaicism in a 15-year-old Wiskott-Aldrich syndrome (WAS; 301000) patient due to a second-hit mutation in the initiation codon of the WAS gene. The germline mutation was a single-basepair deletion in the WAS cDNA, 11delG, which resulted in a frameshift and abrogated protein expression (Gly4fsTer40). The patient had originally been described by Sasahara et al. (2000). Seven years after chemotherapy for Hodgkin disease, expression of WASP was detected in a fraction of T and NK cells. These WASP-expressing cells had a 1A-T (M1_P5del) mutation in the initiation codon. Du et al. (2006) hypothesized that the second-site mutation in the initiation codon resulted in alternative translation initiation from the second ATG that is located downstream of the germline single-nucleotide deletion. The patient was in complete remission at the time of the report of Du et al. (2006). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 WISKOTT-ALDRICH SYNDROME, SOMATIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, 1A-T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776742,
|
|
|
|
|
|
|
|
ClinVar: RCV000011869
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the somatic 1A-T mutation in the WAS gene that was found in compound heterozygous state in a patient with Wiskott-Aldrich syndrome (WAS; 301000) by Du et al. (2006), see 300392.0019. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, 2-BP DEL, 73AC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1602176299,
|
|
|
|
|
|
|
|
ClinVar: RCV000011883
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an affected grandson of a female first cousin of the 3 patients described originally by Wiskott (1937) with Wiskott-Aldrich syndrome (WAS; 301000), Binder et al. (2006) found a deletion of 2 nucleotides at positions 73 and 74 in exon 1 (coding sequence, 73-74delAC; the first nucleotide is the A of the ATG translation initiation codon) of the WAS gene. The deletion resulted in a frameshift that starts with amino acid 25; the shifted reading frame was open for another 11 amino acids before it resulted in a stop codon. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, 1-BP DEL, 758A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2147264989,
|
|
|
|
|
|
|
|
ClinVar: RCV001566101, RCV002463367
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 15-year-old boy with Wiskott-Aldrich syndrome (WAS; 301000), Dobbs et al. (2007) identified a 1-bp deletion (758delA) in codon 242 of exon 7 of the WAS gene. The proband had 2 affected maternal cousins who were found to have a different but contiguous single basepair deletion, a C deletion in codon 241 of exon 7 (300392.0023). The mother of the proband was heterozygous for the A deletion, whereas her 3 sisters, including the mother of the affected cousins, were heterozygous for the C deletion. Their maternal grandmother was found to be a mosaic for deletions, which both occurred on the haplotype from the unaffected maternal great-grandfather, consistent with a bichromatid mutation in a male gamete. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 WISKOTT-ALDRICH SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, 1-BP DEL, CODON 241, C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2147264981,
|
|
|
|
|
|
|
|
ClinVar: RCV001390444, RCV001552729, RCV002463366
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 15-year-old boy with Wiskott-Aldrich syndrome (WAS; 301000), Dobbs et al. (2007) identified a 1-bp deletion (758delA; 300392.0022) in codon 242 of exon 7 of the WAS gene. The proband had 2 affected maternal cousins who were found to have a different but contiguous single basepair deletion, a C deletion in codon 241 of exon 7 (300392.0023). The mother of the proband was heterozygous for the A deletion, whereas her 3 sisters, including the mother of the affected cousins, were heterozygous for the C deletion. Their maternal grandmother was found to be a mosaic for deletions, which both occurred on the haplotype from the unaffected maternal great-grandfather, consistent with a bichromatid mutation in a male gamete. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 NEUTROPENIA, SEVERE CONGENITAL, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, SER272PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906716,
|
|
|
|
|
|
|
|
ClinVar: RCV000022858, RCV003764631
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with severe congenital neutropenia (SCNX; 300299), Ancliff et al. (2006) identified a T-to-C transition in the WAS gene, resulting in a ser272-to-pro (S272P) substitution in the GTPase-binding domain. The mutation was not detected in 50 controls. His mother, maternal aunt, and maternal grandmother were carriers of the mutation, and all had apparent nonrandom X-inactivation with 98%, 85%, and 79% expression, respectively, of the wildtype allele. Functional analysis revealed that the S272P mutation resulted in increased WAS activity and produced marked abnormalities of cytoskeletal structure and dynamics. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 NEUTROPENIA, SEVERE CONGENITAL, X-LINKED</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WAS, ILE294THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906717,
|
|
|
|
|
|
|
|
ClinVar: RCV000022859, RCV001058962, RCV001268500, RCV003407355, RCV004782021
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy of Zairian parentage with severe congenital neutropenia (SCNX; 300299), Ancliff et al. (2006) identified a T-to-C transition in the WAS gene, resulting in an ile294-to-thr (I294T) substitution in the GTPase-binding domain. The mutation was not detected in 100 randomly chosen controls or in 100 individuals of African origin. The X-chromosome inactivation pattern of his carrier mother showed a mean ratio of 79%:21% (wildtype:mutant alleles), with no significant differences between the inactivation pattern in purified neutrophils and CD3(+) cells. Functional analysis revealed that the I294T mutation resulted in increased WAS activity and produced marked abnormalities of cytoskeletal structure and dynamics. </p><p>In affected males and carrier females from a large Irish kindred segregating X-linked congenital neutropenia, originally reported by Cryan et al. (1988), Beel et al. (2008) identified an 882T-C transition in exon 9 of the WAS gene, resulting in the I294T mutation. Functional analysis confirmed that the I294T mutant is constitutively active toward actin polymerization. Four of 6 female carriers showed random X-chromosome inactivation. Two female carriers showed no consistent pattern of asymmetric X-chromosome inactivation. </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">
|
|
Aldrich et al. (1954); Greer et al. (1989); Greer et al. (1990); Kwan
|
|
et al. (1989); Kwan et al. (1988)
|
|
</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">
|
|
Aldrich, R. A., Steinberg, A. G., Campbell, D. C.
|
|
<strong>Pedigree demonstrating a sex-linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea.</strong>
|
|
Pediatrics 13: 133-139, 1954.
|
|
|
|
|
|
[PubMed: 13133561]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ancliff, P. J., Blundell, M. P., Cory, G. O., Calle, Y., Worth, A., Kempski, H., Burns, S., Jones, G. E., Sinclair, J., Kinnon, C., Hann, I. M., Gale, R. E., Linch, D. C., Thrasher, A. J.
|
|
<strong>Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia.</strong>
|
|
Blood 108: 2182-2189, 2006.
|
|
|
|
|
|
[PubMed: 16804117]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2006-01-010249]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Andreu, N., Carreras, C., Prieto, F., Estivill, X., Volpini, V., Fillat, C.
|
|
<strong>Identification and characterization of a novel splice-site mutation in a patient with Wiskott-Aldrich syndrome.</strong>
|
|
J. Hum. Genet. 48: 590-593, 2003.
|
|
|
|
|
|
[PubMed: 14566484]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10038-003-0083-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ariga, T., Yamada, M., Sakiyama, Y., Tatsuzawa, O.
|
|
<strong>A case of Wiskott-Aldrich syndrome with dual mutations in exon 10 of the WASP gene: an additional de novo one-base insertion, which restores frame shift due to an inherent one-base deletion, detected in the major population of the patient's peripheral blood lymphocytes. (Letter)</strong>
|
|
Blood 92: 699-701, 1998.
|
|
|
|
|
|
[PubMed: 9657775]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Beel, K., Cotter, M. M., Blatny, J., Bond, J., Lucus, G., Green, F., Vanduppen, V., Leung, D. W., Rooney, S., Smith, O. P., Rosen, M. K., Vandenberghe, P.
|
|
<strong>A large kindred with X-linked neutropenia with an I294T mutation of the Wiskott-Aldrich syndrome gene.</strong>
|
|
Brit. J. Haemat. 144: 120-126, 2008.
|
|
|
|
|
|
[PubMed: 19006568]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.2008.07416.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Binder, V., Albert, M. H., Kabus, M., Bertone, M., Meindl, A., Belohradsky, B. H.
|
|
<strong>The genotype of the original Wiskott phenotype.</strong>
|
|
New Eng. J. Med. 355: 1790-1793, 2006.
|
|
|
|
|
|
[PubMed: 17065640]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa062520]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Boztug, K., Germeshausen, M., Avedillo Diez, I., Gulacsy, V., Diestelhorst, J., Ballmaier, M., Welte, K., Marodi, L., Chernyshova, L. I., Klein, C.
|
|
<strong>Multiple independent second-site mutations in two siblings with somatic mosaicism for Wiskott-Aldrich syndrome.</strong>
|
|
Clin. Genet. 74: 68-74, 2008.
|
|
|
|
|
|
[PubMed: 18479478]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2008.01019.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cheng, H.-C., Skehan, B. M., Campellone, K. G., Leong, J. M., Rosen, M, K.
|
|
<strong>Structural mechanism of WASP activation by the enterohaemorrhagic E. coli effector EspFU.</strong>
|
|
Nature 454: 1009-1013, 2008.
|
|
|
|
|
|
[PubMed: 18650809]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature07160]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cotta-de-Almeida, V., Westerberg, L., Maillard, M. H., Onaldi, D., Wachtel, H., Meelu, P., Chung, U., Xavier, R., Alt, F. W., Snapper, S. B.
|
|
<strong>Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 15424-15429, 2007.
|
|
|
|
|
|
[PubMed: 17878299]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0706881104]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cryan, E. F., Deasy, P. F., Buckley, R. J., Greally, J. F.
|
|
<strong>Congenital neutropenia and low serum immunoglobulin A: description and investigation of a large kindred.</strong>
|
|
Thymus 11: 185-199, 1988.
|
|
|
|
|
|
[PubMed: 3284030]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Saint Basile, G., Lagelouse, R. D., Lambert, N., Schwarz, K., Le Mareck, B., Odent, S., Schlegel, N., Fischer, A.
|
|
<strong>Isolated X-linked thrombocytopenia in two unrelated families is associated with point mutations in the Wiskott-Aldrich syndrome protein gene.</strong>
|
|
J. Pediat. 129: 56-62, 1996.
|
|
|
|
|
|
[PubMed: 8757563]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(96)70190-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Derry, J. M. J., Kerns, J. A., Weinberg, K. I., Ochs, H. D., Volpini, V., Estivill, X., Walker, A. P., Francke, U.
|
|
<strong>WASP gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia.</strong>
|
|
Hum. Molec. Genet. 4: 1127-1135, 1995.
|
|
|
|
|
|
[PubMed: 8528199]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.7.1127]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Derry, J. M. J., Ochs, H. D., Francke, U.
|
|
<strong>Isolation of a novel gene mutated in Wiskott-Aldrich syndrome.</strong>
|
|
Cell 78: 635-644, 1994. Note: Erratum: Cell 79: following 922, 1994.
|
|
|
|
|
|
[PubMed: 8069912]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(94)90528-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Derry, J. M. J., Wiedemann, P., Blair, P., Wang, Y., Kerns, J. A., Lemahieu, V., Godfrey, V. L., Wilkinson, J. E., Francke, U.
|
|
<strong>The mouse homolog of the Wiskott-Aldrich syndrome protein (WASP) gene is highly conserved and maps near the scurfy (sf) mutation on the X chromosome.</strong>
|
|
Genomics 29: 471-477, 1995.
|
|
|
|
|
|
[PubMed: 8666397]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1995.9979]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Devriendt, K., Kim, A. S., Mathijs, G., Frints, S. G. M., Schwartz, M., Van den Oord, J. J., Verhoef, G. E. G., Boogaerts, M. A., Fryns, J.-P., You, D., Rosen, M. K., Vandenberghe, P.
|
|
<strong>Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia.</strong>
|
|
Nature Genet. 27: 313-317, 2001.
|
|
|
|
|
|
[PubMed: 11242115]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/85886]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dobbs, A. K., Yang, T., Farmer, D. M., Howard, V., Conley, M. E.
|
|
<strong>A possible bichromatid mutation in a male gamete giving rise to a female mosaic for two different mutations in the X-linked gene WAS.</strong>
|
|
Clin. Genet. 71: 171-176, 2007.
|
|
|
|
|
|
[PubMed: 17250667]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2007.00748.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Du, W., Kumaki, S., Uchiyama, T., Yachie, A., Looi, C. Y., Kawai, S., Minegishi, M., Ramesh, N., Geha, R. S., Sasahara, Y., Tsuchiya, S.
|
|
<strong>A second-site mutation in the initiation codon of WAS (WASP) results in expansion of subsets of lymphocytes in an Wiskott-Aldrich syndrome patient.</strong>
|
|
Hum. Mutat. 27: 370-375, 2006.
|
|
|
|
|
|
[PubMed: 16511828]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20308]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fillat, C., Espanol, T., Oset, M., Ferrando, M., Estivill, X., Volpini, V.
|
|
<strong>Identification of WASP mutations in 14 Spanish families with Wiskott-Aldrich syndrome.</strong>
|
|
Am. J. Med. Genet. 100: 116-121, 2001.
|
|
|
|
|
|
[PubMed: 11298372]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1228]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Greer, W. L., Mahtani, M. M., Kwong, P. C., Rubin, L. A., Peacocke, M., Willard, H. F., Siminovitch, K. A.
|
|
<strong>Linkage studies of the Wiskott-Aldrich syndrome: polymorphisms at TIMP and the X chromosome centromere are informative markers for genetic prediction.</strong>
|
|
Hum. Genet. 83: 227-230, 1989.
|
|
|
|
|
|
[PubMed: 2571560]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00285161]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Greer, W. L., Shehabeldin, A., Schulman, J., Junker, A., Siminovitch, K. A.
|
|
<strong>Identification of WASP mutations, mutation hotspots and genotype-phenotype disparities in 24 patients with the Wiskott-Aldrich syndrome.</strong>
|
|
Hum. Genet. 98: 685-690, 1996.
|
|
|
|
|
|
[PubMed: 8931701]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050285]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Greer, W. L., Somani, A.-K., Kwong, P. C., Peacocke, M., Rubin, L. A., Siminovitch, K. A.
|
|
<strong>Linkage relationships of the Wiskott-Aldrich syndrome to 10 loci in the pericentromeric region of the human X chromosome.</strong>
|
|
Genomics 6: 568-571, 1990.
|
|
|
|
|
|
[PubMed: 2328995]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(90)90489-h]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hirschhorn, R., Yang, D. R., Puck, J. M., Huie, M. L., Jiang, C.-K., Kurlandsky, L. E.
|
|
<strong>Spontaneous in vivo reversion to normal of an inherited mutation in a patient with adenosine deaminase deficiency.</strong>
|
|
Nature Genet. 13: 290-295, 1996.
|
|
|
|
|
|
[PubMed: 8673127]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0796-290]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ho, L. L., Ayling, J., Prosser, I., Kronenberg, H., Iland, H., Joshua, D.
|
|
<strong>Missense C168T in the Wiskott-Aldrich syndrome protein gene is a common mutation in X-linked thrombocytopenia.</strong>
|
|
Brit. J. Haemat. 112: 76-80, 2001.
|
|
|
|
|
|
[PubMed: 11167787]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.2001.02465.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Humblet-Baron, S., Sather, B., Anover, S., Becker-Herman, S., Kasprowicz, D. J., Khim, S., Nguyen, T., Hudkins-Loya, K., Alpers, C. E., Ziegler, S. F., Ochs, H., Torgerson, T., Campbell, D. J., Rawlings, D. J.
|
|
<strong>Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis.</strong>
|
|
J. Clin. Invest. 117: 407-418, 2007.
|
|
|
|
|
|
[PubMed: 17218989]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI29539]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Imai, K., Morio, T., Zhu, Y., Jin, Y., Itoh, S., Kajiwara, M., Yata, J., Mizutani, S., Ochs, H. D., Nonoyama, S.
|
|
<strong>Clinical course of patients with WASP gene mutations.</strong>
|
|
Blood 103: 456-464, 2004.
|
|
|
|
|
|
[PubMed: 12969986]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2003-05-1480]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Inoue, H., Kurosawa, H., Nonoyama, S., Imai, K., Kumazaki, H., Matsunaga, T., Sato, Y., Sugita, K., Eguchi, M.
|
|
<strong>X-linked thrombocytopenia in a girl.</strong>
|
|
Brit. J. Haemat. 118: 1163-1165, 2002.
|
|
|
|
|
|
[PubMed: 12199801]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.2002.03740.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jin, Y., Mazza, C., Christie, J. R., Giliani, S., Fiorini, M., Mella, P., Gandellini, F., Stewart, D. M., Zhu, Q., Nelson, D. L., Notarangelo, L. D., Ochs, H. D.
|
|
<strong>Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation.</strong>
|
|
Blood 104: 4010-4019, 2004.
|
|
|
|
|
|
[PubMed: 15284122]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2003-05-1592]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kim, A. S., Kakalis, L. T., Abdul-Manan, N., Liu, G. A., Rosen, M. K.
|
|
<strong>Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein.</strong>
|
|
Nature 404: 151-158, 2000.
|
|
|
|
|
|
[PubMed: 10724160]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/35004513]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kolluri, R., Shehabeldin, A., Peacocke, M., Lamhonwah, A.-M., Teichert-Kuliszewska, K., Weissman, S. M., Siminovitch, K. A.
|
|
<strong>Identification of WASP mutations in patients with Wiskott-Aldrich syndrome and isolated thrombocytopenia reveals allelic heterogeneity at the WAS locus.</strong>
|
|
Hum. Molec. Genet. 4: 1119-1126, 1995.
|
|
|
|
|
|
[PubMed: 8528198]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.7.1119]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kolluri, R., Tolias, K. F., Carpenter, C. L., Rosen, F. S., Kirchhausen, T.
|
|
<strong>Direct interaction of the Wiskott-Aldrich syndrome protein with the GTPase Cdc42.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 5615-5618, 1996.
|
|
|
|
|
|
[PubMed: 8643625]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.93.11.5615]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kwan, S. P., Hagemann, T. L., Blaese, R. M., Knutsen, A., Rosen, F. S.
|
|
<strong>Scanning of the Wiskott-Aldrich syndrome (WAS) gene: identification of 18 novel alterations including a possible mutation hotspot at Arg86 resulting in thrombocytopenia, a mild WAS phenotype.</strong>
|
|
Hum. Molec. Genet. 4: 1995-1998, 1995.
|
|
|
|
|
|
[PubMed: 8595430]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.10.1995]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kwan, S.-P., Hagemann, T. L., Radtke, B. E., Blaese, R. M., Rosen, F. S.
|
|
<strong>Identification of mutations in the Wiskott-Aldrich syndrome gene and characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent to the disease gene.</strong>
|
|
Proc. Nat. Acad. Sci. 92: 4706-4710, 1995.
|
|
|
|
|
|
[PubMed: 7753869]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.92.10.4706]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kwan, S.-P., Lehner, T., Lu, B., Raghu, G., Blaese, M., Sandkuyl, L. A., Ott, J., Fraser, N., Boyd, Y., Craig, I. W., Fischer, S., Rosen, F.
|
|
<strong>Linkage of DXS255 to the Wiskott Aldrich syndrome gene. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 51: 1027 only, 1989.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kwan, S.-P., Sandkuyl, L. A., Blaese, M., Kunkel, L. M., Bruns, G., Parmley, R., Skarshaug, S., Page, D. C., Ott, J., Rosen, F. S.
|
|
<strong>Genetic mapping of the Wiskott-Aldrich syndrome with two highly-linked polymorphic DNA markers.</strong>
|
|
Genomics 3: 39-43, 1988.
|
|
|
|
|
|
[PubMed: 2906042]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(88)90156-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lemahieu, V., Gastier, J. M., Francke, U.
|
|
<strong>Novel mutations in the Wiskott-Aldrich syndrome protein gene and their effects on transcriptional, translational, and clinical phenotypes.</strong>
|
|
Hum. Mutat. 14: 54-66, 1999.
|
|
|
|
|
|
[PubMed: 10447259]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1999)14:1<54::AID-HUMU7>3.0.CO;2-E]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lutskiy, M. I., Jones, L. N., Rosen, F. S., Remold-O'Donnell, E.
|
|
<strong>An Alu-mediated deletion at Xp11.23 leading to Wiskott-Aldrich syndrome.</strong>
|
|
Hum. Genet. 110: 515-519, 2002.
|
|
|
|
|
|
[PubMed: 12073025]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-002-0716-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lutskiy, M. I., Sasahara, Y., Kenney, D. M., Rosen, F. S., Remold-O'Donnell, E.
|
|
<strong>Wiskott-Aldrich syndrome in a female.</strong>
|
|
Blood 100: 2763-2768, 2002.
|
|
|
|
|
|
[PubMed: 12351383]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2002-02-0388]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lyon, M. F., Peters, J., Glenister, P. H., Ball, S., Wright, E.
|
|
<strong>The scurfy mouse mutant has previously unrecognized hematological abnormalities and resembles Wiskott-Aldrich syndrome.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 2433-2437, 1990.
|
|
|
|
|
|
[PubMed: 2320565]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.87.7.2433]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maillard, M. H., Cotta-de-Almeida, V., Takeshima, F., Nguyen, D. D., Michetti, P., Nagler, C., Bhan, A. K., Snapper, S. B.
|
|
<strong>The Wiskott-Aldrich syndrome protein is required for the function of CD4+CD25+Foxp3+ regulatory T cells.</strong>
|
|
J. Exp. Med. 204: 381-391, 2007.
|
|
|
|
|
|
[PubMed: 17296786]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1084/jem.20061338]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Marangoni, F., Trifari, S., Scaramuzza, S., Panaroni, C., Martino, S., Notarangelo, L. D., Baz, Z., Metin, A., Cattaneo, F., Villa, A., Aiuti, A., Battaglia, M., Roncarolo, M.-G., Dupre, L.
|
|
<strong>WASP regulates suppressor activity of human and murine CD4+CD25+FOXP3+ natural regulatory T cells.</strong>
|
|
J. Exp. Med. 204: 369-380, 2007.
|
|
|
|
|
|
[PubMed: 17296785]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1084/jem.20061334]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Marchand, J.-B., Kaiser, D. A., Pollard, T. D., Higgs, H. N.
|
|
<strong>Interaction of WASP/Scar proteins with actin and vertebrate Arp2/3 complex.</strong>
|
|
Nature Cell Biol. 3: 76-82, 2001.
|
|
|
|
|
|
[PubMed: 11146629]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/35050590]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Notarangelo, L. D., Mazza, C., Giliani, S., D'Aria, C., Gandellini, F., Ravelli, C., Locatelli, M. G., Nelson, D. L., Ochs, H. D., Notarangelo, L. D.
|
|
<strong>Missense mutations of the WASP gene cause intermittent X-linked thrombocytopenia.</strong>
|
|
Blood 99: 2268-2269, 2002.
|
|
|
|
|
|
[PubMed: 11877312]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood.v99.6.2268]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Orange, J. S., Ramesh, N., Remold-O'Donnell, E., Sasahara, Y., Koopman, L., Byrne, M., Bonilla, F. A., Rosen, F. S., Geha, R. S., Strominger, J. L.
|
|
<strong>Wiskott-Aldrich syndrome protein is required for NK cell cytotoxicity and colocalizes with actin to NK cell-activating immunologic synapses.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 11351-11356, 2002.
|
|
|
|
|
|
[PubMed: 12177428]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.162376099]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Parolini, O., Ressmann, G., Haas, O. A., Pawlowsky, J., Gadner, H., Knapp, W., Holter, W.
|
|
<strong>X-linked Wiskott-Aldrich syndrome in a girl.</strong>
|
|
New Eng. J. Med. 338: 291-295, 1998.
|
|
|
|
|
|
[PubMed: 9445409]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199801293380504]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Puck, J. M., Willard, H. F.
|
|
<strong>X inactivation in females with X-linked disease.</strong>
|
|
New Eng. J. Med. 338: 325-327, 1998.
|
|
|
|
|
|
[PubMed: 9445416]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199801293380611]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sasahara, Y., Kawai, S., Kumaki, S., Ohashi, Y., Minegishi, M., Tsuchiya, S.
|
|
<strong>Novel mutations, no detectable mRNA and familial genetic analysis of the Wiskott-Aldrich syndrome protein gene in six Japanese patients with Wiskott-Aldrich syndrome.</strong>
|
|
Europ. J. Pediat. 159: 23-30, 2000.
|
|
|
|
|
|
[PubMed: 10653325]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004310050005]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sasahara, Y., Rachid, R., Byrne, M. J., de la Fuente, M. A., Abraham, R. T., Ramesh, N., Geha, R. S.
|
|
<strong>Mechanism of recruitment of WASP to the immunological synapse and of its activation following TCR ligation.</strong>
|
|
Molec. Cell 10: 1269-1281, 2002.
|
|
|
|
|
|
[PubMed: 12504004]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s1097-2765(02)00728-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schindelhauer, D., Weiss, M., Hellebrand, H., Golla, A., Hergersberg, M., Seger, R., Belohradsky, B. H., Meindl, A.
|
|
<strong>Wiskott-Aldrich syndrome: no strict genotype-phenotype correlations but clustering of missense mutations in the amino-terminal part of the WASP gene product.</strong>
|
|
Hum. Genet. 98: 68-76, 1996.
|
|
|
|
|
|
[PubMed: 8682510]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050162]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scott, M. P., Zappacosta, F., Kim, E. Y., Annan, R. S., Miller, W. T.
|
|
<strong>Identification of novel SH3 domain ligands for the Src family kinase Hck: Wiskott-Aldrich syndrome protein (WASP), WASP-interacting protein (WIP), and ELMO1.</strong>
|
|
J. Biol. Chem. 277: 28238-28246, 2002.
|
|
|
|
|
|
[PubMed: 12029088]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M202783200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Siminovitch, K. A., Greer, W. L., Novogrodsky, A., Axelsson, B., Somani, A.-K., Peacocke, M.
|
|
<strong>A diagnostic assay for the Wiskott-Aldrich syndrome and its variant forms.</strong>
|
|
J. Investig. Med. 43: 159-169, 1995.
|
|
|
|
|
|
[PubMed: 7735919]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Snapper, S. B., Rosen, F. S., Mizoguchi, E., Cohen, P., Khan, W., Liu, C. H., Hagemann, T. L., Kwan, S. P., Ferrini, R., Davidson, L., Bhan, A. K., Alt, F. W.
|
|
<strong>Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation.</strong>
|
|
Immunity 9: 81-91, 1998.
|
|
|
|
|
|
[PubMed: 9697838]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s1074-7613(00)80590-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Snapper, S. B., Rosen, F. S.
|
|
<strong>The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization.</strong>
|
|
Annu. Rev. Immun. 17: 905-929, 1999.
|
|
|
|
|
|
[PubMed: 10358777]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1146/annurev.immunol.17.1.905]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stewart, D. M., Treiber-Held, S., Kurman, C. C., Facchetti, F., Notarangelo, L. D., Nelson, D. L.
|
|
<strong>Studies of the expression of the Wiskott-Aldrich syndrome protein.</strong>
|
|
J. Clin. Invest. 97: 2627-2634, 1996.
|
|
|
|
|
|
[PubMed: 8647957]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI118712]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Symons, M., Derry, J. M. J., Karlak, B., Jiang, S., Lemahieu, V., McCormick, F., Francke, U., Abo, A.
|
|
<strong>Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization.</strong>
|
|
Cell 84: 723-734, 1996.
|
|
|
|
|
|
[PubMed: 8625410]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)81050-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thompson, L. J., Lalloz, M. R. A., Layton, D. M.
|
|
<strong>Unique and recurrent WAS gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia.</strong>
|
|
Blood Cells Molec. Dis. 25: 218-226, 1999.
|
|
|
|
|
|
[PubMed: 10575547]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bcmd.1999.0247]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vallee, T. C., Glasmacher, J. S., Buchner, H., Arkwright, P. D., Behrends, U., Bondarenko, A., Browning, M. J., Buchbinder, D., Cattoni, A., Chernyshova, L., Ciznar, P., Cole, T., and 43 others.
|
|
<strong>Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival.</strong>
|
|
Blood 143: 2504-2516, 2024.
|
|
|
|
|
|
[PubMed: 38579284]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood.2023021411]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Villa, A., Notarangelo, L., Macchi, P., Mantuano, E., Cavagni, G., Brugnoni, D., Strina, D., Patrosso, M. C., Ramenghi, U., Sacco, M. G., Ugazio, A., Vezzoni, P.
|
|
<strong>X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene.</strong>
|
|
Nature Genet. 9: 414-417, 1995.
|
|
|
|
|
|
[PubMed: 7795648]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0495-414]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Volkman, B. F., Prehoda, K. E., Scott, J. A., Peterson, F. C., Lim, W. A.
|
|
<strong>Structure of the N-WASP EVH1 domain-WIP complex: insight into the molecular basis of Wiskott-Aldrich syndrome.</strong>
|
|
Cell 111: 565-576, 2002.
|
|
|
|
|
|
[PubMed: 12437929]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(02)01076-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wada, T., Konno, A., Schurman, S. H., Garabedian, E. K., Anderson, S. M., Kirby, M., Nelson, D. L., Candotti, F.
|
|
<strong>Second-site mutation in the Wiskott-Aldrich syndrome (WAS) protein gene causes somatic mosaicism in two WAS siblings.</strong>
|
|
J. Clin. Invest. 111: 1389-1397, 2003.
|
|
|
|
|
|
[PubMed: 12727931]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI15485]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wada, T., Schurman, S. H., Jagadeesh, G. J., Garabedian, E. K., Nelson, D. L., Candotti, F.
|
|
<strong>Multiple patients with revertant mosaicism in a single Wiskott-Aldrich syndrome family.</strong>
|
|
Blood 104: 1270-1272, 2004.
|
|
|
|
|
|
[PubMed: 15142877]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1182/blood-2004-03-0846]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wada, T., Schurman, S. H., Otsu, M., Garabedian, E. K., Ochs, H. D., Nelson, D. L., Candotti, F.
|
|
<strong>Somatic mosaicism in Wiskott-Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism.</strong>
|
|
Proc. Nat. Acad. Sci. 98: 8697-8702, 2001.
|
|
|
|
|
|
[PubMed: 11447283]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.151260498]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Waisfisz, Q., Morgan, N. V., Savino, M., de Winter, J. P., van Berkel, C. G. M., Hoatlin, M. E., Ianzano, L., Gibson, R. A., Arwert, F., Savoia, A., Mathew, C. G., Pronk, J. C., Joenje, H.
|
|
<strong>Spontaneous functional correction of homozygous Fanconi anaemia alleles reveals novel mechanistic basis for reverse mosaicism.</strong>
|
|
Nature Genet. 22: 379-383, 1999.
|
|
|
|
|
|
[PubMed: 10431244]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/11956]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wengler, G., Gorlin, J. B., Williamson, J. M., Rosen, F. S., Bing, D. H.
|
|
<strong>Nonrandom inactivation of the X chromosome in early lineage hematopoietic cells in carriers of Wiskott-Aldrich syndrome.</strong>
|
|
Blood 85: 2471-2477, 1995.
|
|
|
|
|
|
[PubMed: 7537115]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wengler, G. S., Notarangelo, L. D., Berardelli, S., Pollonni, G., Mella, P., Fasth, A., Ugazio, A. G., Parolini, O.
|
|
<strong>High prevalence of nonsense, frame shift, and splice-site mutations in 16 patients with full-blown Wiskott-Aldrich syndrome.</strong>
|
|
Blood 86: 3648-3654, 1995.
|
|
|
|
|
|
[PubMed: 7579329]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Westerberg, L. S., Meelu, P., Baptista, M., Eston, M. A., Adamovich, D. A., Cotta-de-Almeida, V., Seed, B., Rosen, M. K., Vandenberghe, P., Thrasher, A. J., Klein, C., Alt, F. W., Snapper, S. B.
|
|
<strong>Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes.</strong>
|
|
J. Exp. Med. 207: 1145-1152, 2010.
|
|
|
|
|
|
[PubMed: 20513746]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1084/jem.20091245]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wiskott, A.
|
|
<strong>Familiarer, angeborener Morbus Werlhofii?</strong>
|
|
Mschr. Kinderheilk. 68: 212-216, 1937.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhu, Q., Watanabe, C., Liu, T., Hollenbaugh, D., Blaese, R. M., Kanner, S. B., Aruffo, A., Ochs, H. D.
|
|
<strong>Wiskott-Aldrich syndrome/X-linked thrombocytopenia: WASP gene mutations, protein expression, and phenotype.</strong>
|
|
Blood 90: 2680-2689, 1997.
|
|
|
|
|
|
[PubMed: 9326235]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhu, Q., Zhang, M., Blaese, R. M., Derry, J. M. J., Junker, A., Francke, U., Chen, S.-H., Ochs, H. D.
|
|
<strong>The Wiskott-Aldrich syndrome and X-linked congenital thrombocytopenia are caused by mutations of the same gene.</strong>
|
|
Blood 86: 3797-3804, 1995.
|
|
|
|
|
|
[PubMed: 7579347]
|
|
|
|
|
|
|
|
</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">
|
|
Ada Hamosh - updated : 01/07/2025<br>Paul J. Converse - updated : 11/9/2012<br>Paul J. Converse - updated : 1/12/2012<br>Marla J. F. O'Neill - updated : 5/20/2011<br>Cassandra L. Kniffin - updated : 5/13/2009<br>Ada Hamosh - updated : 9/2/2008<br>Marla J. F. O'Neill - updated : 11/21/2007<br>Paul J. Converse - updated : 11/14/2007<br>Paul J. Converse - updated : 8/7/2007<br>Paul J. Converse - updated : 3/19/2007<br>Victor A. McKusick - updated : 11/30/2006<br>Anne M. Stumpf - updated : 6/13/2006<br>Victor A. McKusick - updated : 6/6/2006<br>Victor A. McKusick - updated : 12/10/2004<br>Victor A. McKusick - updated : 4/16/2004<br>Victor A. McKusick - updated : 12/23/2003<br>Stylianos E. Antonarakis - updated : 4/28/2003<br>Victor A. McKusick - updated : 1/10/2003<br>Stylianos E. Antonarakis - updated : 11/25/2002<br>Victor A. McKusick - updated : 10/21/2002<br>Victor A. McKusick - updated : 10/9/2002<br>Victor A. McKusick - updated : 6/7/2002<br>Victor A. McKusick - updated : 5/13/2002
|
|
</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 : 5/8/2002
|
|
</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 : 01/08/2025<br>alopez : 01/08/2025<br>alopez : 01/07/2025<br>carol : 03/11/2021<br>carol : 01/16/2018<br>alopez : 09/22/2016<br>terry : 03/28/2013<br>mgross : 11/19/2012<br>mgross : 11/19/2012<br>terry : 11/9/2012<br>carol : 3/26/2012<br>mgross : 2/23/2012<br>terry : 1/27/2012<br>mgross : 1/18/2012<br>terry : 1/12/2012<br>terry : 1/12/2012<br>wwang : 6/8/2011<br>wwang : 6/7/2011<br>carol : 6/7/2011<br>wwang : 5/25/2011<br>terry : 5/20/2011<br>wwang : 5/13/2009<br>alopez : 9/15/2008<br>terry : 9/2/2008<br>alopez : 4/23/2008<br>carol : 11/26/2007<br>terry : 11/21/2007<br>mgross : 11/15/2007<br>mgross : 11/15/2007<br>terry : 11/14/2007<br>mgross : 8/23/2007<br>terry : 8/7/2007<br>mgross : 3/22/2007<br>terry : 3/19/2007<br>alopez : 12/8/2006<br>terry : 11/30/2006<br>terry : 11/3/2006<br>joanna : 11/2/2006<br>alopez : 6/13/2006<br>terry : 6/6/2006<br>terry : 8/3/2005<br>tkritzer : 12/27/2004<br>terry : 12/10/2004<br>mgross : 12/6/2004<br>alopez : 4/20/2004<br>terry : 4/16/2004<br>tkritzer : 2/18/2004<br>carol : 12/24/2003<br>terry : 12/23/2003<br>mgross : 4/28/2003<br>tkritzer : 1/23/2003<br>tkritzer : 1/13/2003<br>terry : 1/10/2003<br>mgross : 11/25/2002<br>carol : 10/22/2002<br>tkritzer : 10/21/2002<br>tkritzer : 10/21/2002<br>tkritzer : 10/21/2002<br>tkritzer : 10/17/2002<br>tkritzer : 10/9/2002<br>tkritzer : 10/9/2002<br>alopez : 6/13/2002<br>terry : 6/7/2002<br>alopez : 5/21/2002<br>alopez : 5/21/2002<br>terry : 5/13/2002<br>carol : 5/13/2002<br>carol : 5/13/2002<br>ckniffin : 5/10/2002<br>ckniffin : 5/9/2002
|
|
</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>
|
|
|
|
|