5334 lines
468 KiB
Text
5334 lines
468 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
|
|
|
|
- *605802 - ZINC FINGER E BOX-BINDING HOMEOBOX 2; ZEB2
|
|
|
|
|
|
- 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=605802"><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">*605802</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#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/605802">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=ENSG00000169554;t=ENST00000627532" 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=9839" 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=605802" 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=ENSG00000169554;t=ENST00000627532" 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_001171653,NM_014795,NR_033258" 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_014795" 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=605802" 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=05780&isoform_id=05780_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/ZEB2" 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/3970868,6841104,7662184,13124503,13548683,14717819,54114889,54114891,62702346,62702353,117558044,117558786,119631980,119631981,119631982,221040442,284413746,929654048" 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/O60315" 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=9839" 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=ENSG00000169554;t=ENST00000627532" 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=ZEB2" 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=ZEB2" 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+9839" 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/ZEB2" 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:9839" 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/9839" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr2&hgg_gene=ENST00000627532.3&hgg_start=144384081&hgg_end=144520119&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:14881" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:14881" 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/zeb2" 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=605802[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=605802[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/ZEB2/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/ENSG00000169554" 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=ZEB2" 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=ZEB2" 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=ZEB2" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=ZEB2&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/PA162409612" 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:14881" 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/FBgn0004606.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:1344407" 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/ZEB2#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:1344407" 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/9839/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://omia.org/OMIA001736/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=9839" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00006970;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-070912-553" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:9839" 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=ZEB2&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> 703535000<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>
|
|
605802
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
ZINC FINGER E BOX-BINDING HOMEOBOX 2; ZEB2
|
|
|
|
</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">
|
|
ZINC FINGER HOMEOBOX 1B; ZFHX1B<br />
|
|
SMAD-INTERACTING PROTEIN 1; SMADIP1<br />
|
|
SIP1<br />
|
|
KIAA0569
|
|
</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=ZEB2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ZEB2</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/2/673?start=-3&limit=10&highlight=673">2q22.3</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:144384081-144520119&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">2:144,384,081-144,520,119</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
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/2/673?start=-3&limit=10&highlight=673">
|
|
2q22.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Mowat-Wilson syndrome
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/235730"> 235730 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/605802" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/605802" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>The ZEB2 gene is a member of the ZEB1 (<a href="/entry/189909">189909</a>)/Drosophila Zfh1 family of 2-handed zinc finger/homeodomain proteins and functions as a DNA-binding transcriptional repressor that interacts with activated SMADs (see <a href="/entry/601595">601595</a>), the transducers of TGF-beta (<a href="/entry/190180">190180</a>) signaling, and interacts with the nucleosome remodeling and histone deacetylation (NURD) complex (<a href="#25" class="mim-tip-reference" title="Verstappen, G., van Grunsven, L. A., Michiels, C., Van de Putte, T., Souopgui, J., Van Damme, J., Bellefroid, E., Vandekerckhove, J., Huylebroeck, D. <strong>Atypical Mowat-Wilson patient confirms the importance of the novel association between ZFHX1B/SIP1 and NuRD corepressor complex.</strong> Hum. Molec. Genet. 17: 1175-1183, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18182442/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18182442</a>] [<a href="https://doi.org/10.1093/hmg/ddn007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18182442">Verstappen et al., 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18182442" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>By sequencing clones obtained from a size-fractionated human brain cDNA library, <a href="#15" class="mim-tip-reference" title="Nagase, T., Ishikawa, K., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.</strong> DNA Res. 5: 31-39, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9628581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9628581</a>] [<a href="https://doi.org/10.1093/dnares/5.1.31" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9628581">Nagase et al. (1998)</a> cloned ZEB2, which they designated KIAA0569. The deduced 1,214-amino acid protein shares significant similarity with rat Zeb1. RT-PCR analysis of human tissues detected highest ZEB2 expression in heart, brain, lung, placenta, and kidney, with moderate expression in ovary, skeletal muscle, liver, and small intestine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9628581" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 the yeast 2-hybrid analysis of mouse embryos, <a href="#24" class="mim-tip-reference" title="Verschueren, K., Remacle, J. E., Collart, C., Kraft, H., Baker, B. S., Tylzanowski, P., Nelles, L., Wuytens, G., Su, M.-T., Bodmer, R., Smith, J. C., Huylebroeck, D. <strong>SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5-prime-CACCT sequences in candidate target genes.</strong> J. Biol. Chem. 274: 20489-20498, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10400677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10400677</a>] [<a href="https://doi.org/10.1074/jbc.274.29.20489" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10400677">Verschueren et al. (1999)</a> identified Zeb2, which they called Smadip1. The Smadip1 protein contains a SMAD-binding domain, a homeodomain-like sequence, and 2 separate clusters of zinc fingers, one N-terminal and the other C-terminal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10400677" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Comparison of human and mouse homologs of ZEB2 at nucleotide and amino acid levels revealed 93% and 97% similarities, respectively (<a href="#26" class="mim-tip-reference" title="Wakamatsu, N., Yamada, Y., Yamada, K., Ono, T., Nomura, N., Taniguchi, H., Kitoh, H., Mutoh, N., Yamanaka, T., Mushiake, K., Kato, K., Sonta, S., Nagaya, M. <strong>Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease.</strong> Nature Genet. 27: 369-370, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11279515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11279515</a>] [<a href="https://doi.org/10.1038/86860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11279515">Wakamatsu et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11279515" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By immunohistochemical analysis of mouse embryos, <a href="#20" class="mim-tip-reference" title="Seuntjens, E., Nityanandam, A., Miquelajauregui, A., Debruyn, J., Stryjewska, A., Goebbels, S., Nave, K.-A., Huylebroeck, D., Tarabykin, V. <strong>Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors.</strong> Nature Neurosci. 12: 1373-1380, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19838179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19838179</a>] [<a href="https://doi.org/10.1038/nn.2409" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19838179">Seuntjens et al. (2009)</a> found that Sip1 was expressed in the cortical plate, but not in neural progenitor cells. In the medial/cingulate cortex at late gestation (embryonic day 18.5), Sip1 expression was restricted to cells of the deep cortical layers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19838179" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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">
|
|
<div class="mim-changed mim-change"><p>The ZEB2 gene spans approximately 70 kb and has 10 exons (<a href="#26" class="mim-tip-reference" title="Wakamatsu, N., Yamada, Y., Yamada, K., Ono, T., Nomura, N., Taniguchi, H., Kitoh, H., Mutoh, N., Yamanaka, T., Mushiake, K., Kato, K., Sonta, S., Nagaya, M. <strong>Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease.</strong> Nature Genet. 27: 369-370, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11279515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11279515</a>] [<a href="https://doi.org/10.1038/86860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11279515">Wakamatsu et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11279515" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="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 radiation hybrid analysis, <a href="#15" class="mim-tip-reference" title="Nagase, T., Ishikawa, K., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.</strong> DNA Res. 5: 31-39, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9628581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9628581</a>] [<a href="https://doi.org/10.1093/dnares/5.1.31" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9628581">Nagase et al. (1998)</a> mapped the ZEB2 gene to chromosome 2. <a href="#26" class="mim-tip-reference" title="Wakamatsu, N., Yamada, Y., Yamada, K., Ono, T., Nomura, N., Taniguchi, H., Kitoh, H., Mutoh, N., Yamanaka, T., Mushiake, K., Kato, K., Sonta, S., Nagaya, M. <strong>Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease.</strong> Nature Genet. 27: 369-370, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11279515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11279515</a>] [<a href="https://doi.org/10.1038/86860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11279515">Wakamatsu et al. (2001)</a> mapped the ZEB2 gene to chromosome 2q22. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11279515+9628581" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#24" class="mim-tip-reference" title="Verschueren, K., Remacle, J. E., Collart, C., Kraft, H., Baker, B. S., Tylzanowski, P., Nelles, L., Wuytens, G., Su, M.-T., Bodmer, R., Smith, J. C., Huylebroeck, D. <strong>SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5-prime-CACCT sequences in candidate target genes.</strong> J. Biol. Chem. 274: 20489-20498, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10400677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10400677</a>] [<a href="https://doi.org/10.1074/jbc.274.29.20489" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10400677">Verschueren et al. (1999)</a> found that, although SMADIP1 interacted with the MH2 domain of receptor-regulated SMADs in yeast and in vitro, its interaction with full-length SMADs (see <a href="/entry/601595">601595</a>) in mammalian cells required receptor-mediated SMAD activation. Like delta-EF1, SMADIP1 bound to 5-prime-CACCT sequences in different promoters, including the Xenopus 'brachyury' (Xbra) promoter (<a href="#18" class="mim-tip-reference" title="Remacle, J. E., Kraft, H., Lerchner, W., Wuytens, G., Collart, C., Verschueren, K., Smith, J. C., Huylebroeck, D. <strong>New mode of DNA binding of multi-zinc finger transcription factors: deltaEF1 family members bind with two hands to two target sites.</strong> EMBO J. 18: 5073-5084, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10487759/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10487759</a>] [<a href="https://doi.org/10.1093/emboj/18.18.5073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10487759">Remacle et al., 1999</a>). Overexpression of either full-length SMADIP1 or its C-terminal zinc finger cluster, which bound to the Xbra2 promoter in vitro, prevented expression of the endogenous Xbra gene in early Xenopus embryos. Therefore, SMADIP1 is likely to be a transcriptional repressor that may be involved in the regulation of at least 1 immediate response gene for activin-dependent signal transduction pathways. <a href="#24" class="mim-tip-reference" title="Verschueren, K., Remacle, J. E., Collart, C., Kraft, H., Baker, B. S., Tylzanowski, P., Nelles, L., Wuytens, G., Su, M.-T., Bodmer, R., Smith, J. C., Huylebroeck, D. <strong>SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5-prime-CACCT sequences in candidate target genes.</strong> J. Biol. Chem. 274: 20489-20498, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10400677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10400677</a>] [<a href="https://doi.org/10.1074/jbc.274.29.20489" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10400677">Verschueren et al. (1999)</a> concluded that identification of this SMAD-interacting protein opens routes to investigate the mechanisms by which TGF-beta (<a href="/entry/190180">190180</a>) members exert their effects on expression of target genes in responsive cells and in the vertebrate embryo. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10400677+10487759" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Comijn, J., Berx, G., Vermassen, P., Verschueren, K., van Grunsven, L., Bruyneel, E., Mareel, M., Huylebroeck, D., van Roy, F. <strong>The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion.</strong> Molec. Cell 7: 1267-1278, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11430829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11430829</a>] [<a href="https://doi.org/10.1016/s1097-2765(01)00260-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11430829">Comijn et al. (2001)</a> reported that expression of wildtype but not mutated SIP1 downregulated mammalian E-cadherin (<a href="/entry/192090">192090</a>) transcription via binding to both conserved E2 boxes of the minimal E-cadherin promoter. SIP1 and Snail (SNAI1; <a href="/entry/604238">604238</a>) bound to partly overlapping promoter sequences and showed similar silencing effects. SIP1 could be induced by TGFB treatment and showed high expression in several E-cadherin-negative human carcinoma cell lines. Conditional expression of SIP1 in E-cadherin-positive MDCK cells abrogated E-cadherin-mediated intercellular adhesion and simultaneously induced invasion. The authors concluded that SIP1 therefore appears to be a promoter of invasion in malignant epithelial tumors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11430829" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To explore telomerase regulation, <a href="#11" class="mim-tip-reference" title="Lin, S.-Y., Elledge, S. J. <strong>Multiple tumor suppressor pathways negatively regulate telomerase.</strong> Cell 113: 881-889, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12837246/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12837246</a>] [<a href="https://doi.org/10.1016/s0092-8674(03)00430-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12837246">Lin and Elledge (2003)</a> employed a general genetic screen in HeLa cells to identify negative regulators of TERT (<a href="/entry/187270">187270</a>). They discovered 3 tumor suppressor/oncogene pathways involved in TERT repression, including SIP1, which mediates TGF-beta-regulated repression of TERT. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12837246" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Vandewalle, C., Comijn, J., De Craene, B., Vermassen, P., Bruyneel, E., Andersen, H., Tulchinsky, E., Van Roy, F., Berx, G. <strong>SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions.</strong> Nucleic Acids Res. 33: 6566-6578, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16314317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16314317</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16314317[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/nar/gki965" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16314317">Vandewalle et al. (2005)</a> showed that expression of mouse Sip1 in human epithelial cells caused a morphologic change from an epithelial to a mesenchymal phenotype. Dedifferentiation was accompanied by repression of several cell junction proteins and their corresponding mRNAs. In addition to E-cadherin, other genes encoding crucial proteins of tight junctions, desmosomes, and gap junctions were downregulated by Sip1. Reporter gene assays and chromatin immunoprecipitation demonstrated direct repression of promoters of some of these genes by Sip1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16314317" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>TGF-beta is a key regulator of extracellular matrix collagens in mesangial cells (MCs) in diabetic nephropathy. <a href="#10" class="mim-tip-reference" title="Kato, M., Zhang, J., Wang, M., Lanting, L., Yuan, H., Rossi, J. J., Natarajan, R. <strong>MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors.</strong> Proc. Nat. Acad. Sci. 104: 3432-3437, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360662</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360662[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.0611192104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17360662">Kato et al. (2007)</a> found that TGF-beta increased miR192 (MIRN192; <a href="/entry/610939">610939</a>) levels in primary mouse MCs, and they identified Sip1 as a target of miR192 in mouse MCs. TGF-beta treatment or transfection with miR192 decreased expression of endogenous Sip1 and activity of a reporter construct containing the 3-prime UTR of Sip1. Conversely, inhibition of miR192 enhanced reporter activity, confirming Sip1 to be an miR192 target. Glomeruli isolated from streptozotocin-injected diabetic mice and diabetic db/db mice (see <a href="/entry/601007">601007</a>) showed elevated miR192 levels relative to corresponding nondiabetic controls, which paralleled increased Tgf-beta and Col1a2 (<a href="/entry/120160">120160</a>) expression. Transfection of mouse MCs with miR192 and short hairpin RNAs targeting delta-EF1 synergistically enhanced activity of a reporter construct containing upstream E-box elements of the Col1a2 gene. <a href="#10" class="mim-tip-reference" title="Kato, M., Zhang, J., Wang, M., Lanting, L., Yuan, H., Rossi, J. J., Natarajan, R. <strong>MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors.</strong> Proc. Nat. Acad. Sci. 104: 3432-3437, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360662</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360662[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.0611192104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17360662">Kato et al. (2007)</a> concluded that TGF-beta-mediated collagen regulation in MCs involves crosstalk between miR192 and the E-box repressors delta-EF1 and SIP1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17360662" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Expression of SNAI1 in epithelial cells triggers an epithelial-mesenchyme transition. <a href="#2" class="mim-tip-reference" title="Beltran, M., Puig, I., Pena, C., Garcia, J. M., Alvarez, A. B., Pena, R., Bonilla, F., Garcia de Herreros, A. <strong>A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition.</strong> Genes Dev. 22: 756-769, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18347095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18347095</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18347095[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/10.1101/gad.455708" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18347095">Beltran et al. (2008)</a> showed that synthesis of ZEB2 was upregulated following SNAI1 expression in human cell lines. SNAI1 did not alter ZEB2 mRNA levels, but it prevented processing of a large intron in the 5-prime UTR of ZEB2 that contains an internal ribosome entry site (IRES) necessary for ZEB2 expression. Maintenance of the 5-prime ZEB2 intron was dependent on expression of an antisense transcript that overlapped the 5-prime splice site in the intron. Ectopic overexpression of this antisense transcript in epithelial cells prevented splicing of the ZEB2 5-prime UTR, resulting in elevated ZEB2 protein expression and, consequently, downregulation of E-cadherin mRNA and protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18347095" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Park, S.-M., Gaur, A. B., Lengyel, E., Peter, M. E. <strong>The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2.</strong> Genes Dev. 22: 894-907, 2008. Note: Erratum: Genes Dev. 23: 1378 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18381893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18381893</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18381893[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/10.1101/gad.1640608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18381893">Park et al. (2008)</a> found that expression of the miR200 family of microRNAs (e.g., MIRN200A; <a href="/entry/612090">612090</a>) in human cell lines was associated with an epithelial phenotype and with expression of E-cadherin, an epithelial cell marker. They identified multiple miR200 target sequences in the 3-prime UTRs of the E-cadherin transcriptional repressors ZEB1 and ZEB2. Using the 3-prime UTRs of mouse and human ZEB1 and ZEB2, they showed that endogenous miR200s suppressed ZEB1 and ZEB2 expression. Increasing miR200 levels induced mesenchymal-to-epithelial transition (MET) in human cancer cell lines, reducing their aggressiveness. Conversely, reducing miR200 levels induced epithelial-to-mesenchymal transition (EMT). <a href="#16" class="mim-tip-reference" title="Park, S.-M., Gaur, A. B., Lengyel, E., Peter, M. E. <strong>The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2.</strong> Genes Dev. 22: 894-907, 2008. Note: Erratum: Genes Dev. 23: 1378 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18381893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18381893</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18381893[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/10.1101/gad.1640608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18381893">Park et al. (2008)</a> concluded that the miR200 family regulates EMT/MET by targeting ZEB1 and ZEB2, which control expression of E-cadherin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18381893" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 spectrometry, <a href="#25" class="mim-tip-reference" title="Verstappen, G., van Grunsven, L. A., Michiels, C., Van de Putte, T., Souopgui, J., Van Damme, J., Bellefroid, E., Vandekerckhove, J., Huylebroeck, D. <strong>Atypical Mowat-Wilson patient confirms the importance of the novel association between ZFHX1B/SIP1 and NuRD corepressor complex.</strong> Hum. Molec. Genet. 17: 1175-1183, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18182442/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18182442</a>] [<a href="https://doi.org/10.1093/hmg/ddn007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18182442">Verstappen et al. (2008)</a> found that ZEB2 associated with multiple subunits of the NURD complex, which plays a key role in transcriptional repression. Mi2-beta (CHD4; <a href="/entry/603277">603277</a>) was identified as a specific cofactor for ZEB2-mediated repression of E-cadherin (CDH1; <a href="/entry/192090">192090</a>). The N-terminal 289 amino acids of ZEB2 were sufficient for interaction with NURD complex subunits. In vitro studies in Xenopus oocytes showed broad Zeb2 expression at the gastrula stage, with stronger expression in neural tissues and neural crest cells at the neurula stage, suggesting a role in neural development. Endogenous Mi2-beta expression broadly overlapped Zeb2 expression, and antisense morpholino knockdown of Mi2-beta resulted in reduced Zeb2-mediated repression of Bmp4 (<a href="/entry/112262">112262</a>) and decreased induction of neural marker Ncam (<a href="/entry/116930">116930</a>). Further studies showed that a mutant ZEB2 protein (<a href="#0014">605802.0014</a>), differing in the first 24 amino acids from the wildtype protein and causing a mild form of Mowat-Wilson syndrome (<a href="/entry/235730">235730</a>), was unable to interact with the NURD complex and showed decreased transcriptional repression of Bmp4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18182442" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Uterine quiescence during pregnancy is mediated by increased progesterone, which represses factors involved in contraction. <a href="#19" class="mim-tip-reference" title="Renthal, N. E., Chen, C.-C., Williams. K. C., Gerard, R. D., Prange-Kiel, J., Mendelson, C. R. <strong>miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor.</strong> Proc. Nat. Acad. Sci. 107: 20828-20833, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21079000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21079000</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21079000[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.1008301107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21079000">Renthal et al. (2010)</a> identified MIRN200 family members (MIRN200B, <a href="/entry/612091">612091</a>; MIRN429, <a href="/entry/612094">612094</a>) as microRNAs that mediate myometrial transition to a contractile phenotype. In human and mouse uterus during pregnancy, <a href="#19" class="mim-tip-reference" title="Renthal, N. E., Chen, C.-C., Williams. K. C., Gerard, R. D., Prange-Kiel, J., Mendelson, C. R. <strong>miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor.</strong> Proc. Nat. Acad. Sci. 107: 20828-20833, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21079000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21079000</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21079000[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.1008301107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21079000">Renthal et al. (2010)</a> found that ZEB1 and ZEB2 were transcriptional repressors of the contraction-associated genes connexin-43 (GJA1; <a href="/entry/121014">121014</a>) and the oxytocin receptor (OXTR; <a href="/entry/167055">167055</a>) in myometrial cells. ZEB1 was directly upregulated by progesterone at the ZEB1 promoter. During preterm labor in mice, there was an unregulation of Mirn200b/Mirn429, which downregulated Zeb1 and Zeb2, resulting in derepression of transcription of the contractility-associated proteins. In addition, Zeb1 was found to directly bind and repress Mirn200b/Mirn429, indicating a feedback mechanism. The findings implicated MIRN200B/MIRN429 and their targets, ZEB1 and ZEB2, as unique progesterone-mediated regulators of uterine quiescence and contractility during pregnancy and labor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21079000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 GFP-tagged endogenous Nfil3 (<a href="/entry/605327">605327</a>), <a href="#12" class="mim-tip-reference" title="Liu, T.-T., Kim, S., Desai, P., Kim, D.-H., Huang, X., Ferris, S. T., Wu, R., Ou, F., Egawa, T., Van Dyken, S. J., Diamond, M. S., Johnson, P. F., Kubo, M., Murphy, T. L., Murphy, K. M. <strong>Ablation of cDC2 development by triple mutations within the Zeb2 enhancer.</strong> Nature 607: 142-148, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35732734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35732734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35732734[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/s41586-022-04866-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35732734">Liu et al. (2022)</a> showed that Nfil3 was transiently expressed to drive conventional type-1 dendritic cell (cDC1) lineage specification in mice, but that it was not required to maintain cDC1 identity. Chromatin immunoprecipitation-sequencing analysis and EMSA suggested that Nfil3 drove pre-cDC1 specification by repressing Zeb2 expression by binding to at least 1 of 3 Nfil3-binding sites in the -165 kb Zeb2 enhancer. However, mutation analysis suggested that the Nfil3 binding sites were not required for Zeb2 expression for B-cell and plasmacytoid dendritic cell (pDC) development, but that instead, in addition to Nfil3, they were likely required for binding to 1 or more factors that supported Zeb2 expression for cDC2 and monocyte development. Further analysis showed that C/EBP factors (see CEBPA, <a href="/entry/116897">116897</a>) bound to the 3 Nfil3-binding sites in the -165 kb Zeb2 enhancer to support Zeb2 expression for cDC2 and monocyte development. Mice with mutation of all 3 binding sites retained pDC development, because the mutation did not ablate lymphoid progenitors, and pDCs could arise from both myeloid and lymphoid progenitors. However, mutation of all 3 binding sites ablated Zeb2 expression in myeloid progenitors and caused complete loss of pre-cDC2 specification and mature cDC2 development in mice, because Zeb2 expression was required only for pre-cDC2 specification, but not for maintenance of mature cDC2s. Mice with the triple mutation did not generate T-helper-2 (Th2) cell responses against Heligmosomoides polygyrus infection, indicating that cDC2s, but not monocytes, were required for Th2 responses. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35732734" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>In patients with Hirschsprung disease associated with microcephaly, mental retardation, hypertelorism, submucous cleft palate, and short stature, consistent with Mowat-Wilson syndrome (MOWS; <a href="/entry/235730">235730</a>), <a href="#26" class="mim-tip-reference" title="Wakamatsu, N., Yamada, Y., Yamada, K., Ono, T., Nomura, N., Taniguchi, H., Kitoh, H., Mutoh, N., Yamanaka, T., Mushiake, K., Kato, K., Sonta, S., Nagaya, M. <strong>Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease.</strong> Nature Genet. 27: 369-370, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11279515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11279515</a>] [<a href="https://doi.org/10.1038/86860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11279515">Wakamatsu et al. (2001)</a> identified nonsense or frameshift mutations in the SMADIP1 gene. These mutations represented null alleles, suggesting that haploinsufficiency for SMADIP1 is sufficient to cause this phenotype. <a href="#26" class="mim-tip-reference" title="Wakamatsu, N., Yamada, Y., Yamada, K., Ono, T., Nomura, N., Taniguchi, H., Kitoh, H., Mutoh, N., Yamanaka, T., Mushiake, K., Kato, K., Sonta, S., Nagaya, M. <strong>Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease.</strong> Nature Genet. 27: 369-370, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11279515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11279515</a>] [<a href="https://doi.org/10.1038/86860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11279515">Wakamatsu et al. (2001)</a> found that the SMADIP1 gene resides in a segment on 2q22 deleted in 3 patients with the Hirschsprung disease-mental retardation syndrome. They concluded that the SMADIP1 gene appears to be essential to embryonic neural and neural crest development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11279515" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To investigate the breadth of clinical variation associated with mutations in ZFHX1B, <a href="#27" class="mim-tip-reference" title="Yamada, K., Yamada, Y., Nomura, N., Miura, K., Wakako, R., Hayakawa, C., Matsumoto, A., Kumagai, T., Yoshimura, I., Miyazaki, S., Kato, K., Sonta, S., Ono, H., Yamanaka, T., Nagaya, M., Wakamatsu, N. <strong>Nonsense and frameshift mutations in ZFHX1B, encoding Smad-interacting protein 1, cause a complex developmental disorder with a great variety of clinical features.</strong> Am. J. Hum. Genet. 69: 1178-1185, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11592033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11592033</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11592033[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/324343" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11592033">Yamada et al. (2001)</a> studied DNA samples from 6 patients with clinical features similar to those described for ZFHX1B deficiency, except that they did not have Hirschsprung disease. The results showed the R695X mutation (<a href="#0002">605802.0002</a>) to be present in 3 cases, with 3 novel mutations being identified in the other 3 patients. All mutations occurred in 1 allele and were de novo events. The results demonstrated that ZFHX1B deficiency is an autosomal dominant complex developmental disorder and that individuals with functional null mutations present with mental retardation, delayed motor development, epilepsy, and a wide spectrum of clinically heterogeneous features suggestive of neurocristopathies at the cephalic, cardiac, and vagal levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11592033" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Amiel, J., Espinosa-Parrilla, Y., Steffann, J., Gosset, P., Pelet, A., Prieur, M., Boute, O., Choiset, A., Lacombe, D., Philip, N., Le Merrer, M., Tanaka, H., Till, M., Touraine, R., Toutain, A., Vekemans, M., Munnich, A., Lyonnet, S. <strong>Large-scale deletions and SMADIP1 truncating mutations in syndromic Hirschsprung disease with involvement of midline structures.</strong> Am. J. Hum. Genet. 69: 1370-1377, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11595972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11595972</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11595972[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/324342" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11595972">Amiel et al. (2001)</a> found that 8 of 19 patients with Hirschsprung disease and mental retardation had large-scale ZFHX1B deletions or truncating mutations. These results allowed further delineation of the spectrum of malformations ascribed to haploinsufficiency of this gene, which includes frequent features such as hypospadias and agenesis of the corpus callosum. Thus, the ZFHX1B gene, which encodes a transcriptional corepressor of Smad target genes, may play a role not only in the patterning of neural crest-derived cells and of the central nervous system but also in the development of midline structures in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11595972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Zweier, C., Albrecht, B., Mitulla, B., Behrens, R., Beese, M., Gillessen-Kaesbach, G., Rott, H.-D., Rauch, A. <strong>'Mowat-Wilson' syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.</strong> Am. J. Med. Genet. 108: 177-181, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891681</a>]" pmid="11891681">Zweier et al. (2002)</a> analyzed the ZFHX1B gene in 5 patients, 3 of whom had Hirschsprung disease syndrome, 2 with and 1 without the facial phenotype described by <a href="#14" class="mim-tip-reference" title="Mowat, D. R., Croaker, G. D. H., Cass, D. T., Kerr, B. A., Chaitow, J., Ades, L. C., Chia, N. L., Wilson, M. J. <strong>Hirschsprung disease, microcephaly, mental retardation, and characteristic facial features: delineation of a new syndrome and identification of a locus at chromosome 2q22-q23.</strong> J. Med. Genet. 35: 617-623, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9719364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9719364</a>] [<a href="https://doi.org/10.1136/jmg.35.8.617" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9719364">Mowat et al. (1998)</a>, and 2 of whom had the distinct facial gestalt without Hirschsprung disease. <a href="#29" class="mim-tip-reference" title="Zweier, C., Albrecht, B., Mitulla, B., Behrens, R., Beese, M., Gillessen-Kaesbach, G., Rott, H.-D., Rauch, A. <strong>'Mowat-Wilson' syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.</strong> Am. J. Med. Genet. 108: 177-181, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891681</a>]" pmid="11891681">Zweier et al. (2002)</a> excluded large deletions in all 5 patients and found truncating ZFHX1B mutations (<a href="#0007">605802.0007</a>-<a href="#0010">605802.0010</a>) in all 4 patients with the characteristic facial phenotype but not in the patient with syndromic Hirschsprung disease without the distinct facial appearance. <a href="#29" class="mim-tip-reference" title="Zweier, C., Albrecht, B., Mitulla, B., Behrens, R., Beese, M., Gillessen-Kaesbach, G., Rott, H.-D., Rauch, A. <strong>'Mowat-Wilson' syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.</strong> Am. J. Med. Genet. 108: 177-181, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891681</a>]" pmid="11891681">Zweier et al. (2002)</a> suggested the name Mowat-Wilson syndrome (<a href="/entry/235730">235730</a>) for the clinical entity of distinct facial appearance, mental retardation, and variable multiple congenital anomalies (MCA). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9719364+11891681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Ishihara, N., Yamada, K., Yamada, Y., Miura, K., Kato, J., Kuwabara, N., Hara, Y., Kobayashi, Y., Hoshino, K., Nomura, Y., Mimaki, M., Ohya, K., and 16 others. <strong>Clinical and molecular analysis of Mowat-Wilson syndrome associated with ZFHX1B mutations and deletions at 2q22-q24.1. (Letter)</strong> J. Med. Genet. 41: 387-393, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15121779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15121779</a>] [<a href="https://doi.org/10.1136/jmg.2003.016154" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15121779">Ishihara et al. (2004)</a> identified 5 novel nonsense and frameshift mutations in the ZFHX1B gene in patients with Mowat-Wilson syndrome and characterized the clinical features and molecular basis of a total of 27 cases with mutations or deletions in ZFHX1B. All of the deletions were of paternal origin, and clinical features in cases with deletions of up to about 5 Mb overlapped those found in cases with nonsense and frameshift mutations. However, 2 of their patients with large deletions (10.42 Mb and 8.83 Mb) had significantly delayed psychomotor development, and 1 of them also had a cleft palate and complicated heart disease, features not previously reported in patients with Mowat-Wilson syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15121779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#30" class="mim-tip-reference" title="Zweier, C., Horn, D., Kraus, C., Rauch, A. <strong>Atypical ZFHX1B mutation associated with a mild Mowat-Wilson syndrome phenotype.</strong> Am. J. Med. Genet. 140A: 869-872, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16532472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16532472</a>] [<a href="https://doi.org/10.1002/ajmg.a.31196" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16532472">Zweier et al. (2006)</a> reported a 5-year-old boy with a facial gestalt similar to that seen in Mowat-Wilson syndrome but who exhibited an unusually mild phenotype and in whom they identified heterozygosity for a splice site mutation in the ZFHX1B gene (<a href="#0014">605802.0014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16532472" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Heinritz, W., Zweier, C., Froster, U. G., Strenge, S., Kujat, A., Syrbe, S., Rauch, A., Schuster, V. <strong>A missense mutation in the ZFHX1B gene associated with an atypical Mowat-Wilson syndrome phenotype.</strong> Am. J. Med. Genet. 140A: 1223-1227, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16688751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16688751</a>] [<a href="https://doi.org/10.1002/ajmg.a.31267" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16688751">Heinritz et al. (2006)</a> described a 2.5-year-old boy with a heterozygous missense mutation in the ZFHX1B gene (<a href="#0015">605802.0015</a>) who had bilateral cleft lip and palate and brachytelephalangy, features unusual in Mowat-Wilson syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16688751" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Dastot-Le Moal, F., Wilson, M., Mowat, D., Collot, N., Niel, F., Goossens, M. <strong>ZFHX1B mutations in patients with Mowat-Wilson syndrome.</strong> Hum. Mutat. 28: 313-321, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17203459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17203459</a>] [<a href="https://doi.org/10.1002/humu.20452" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17203459">Dastot-Le Moal et al. (2007)</a> stated that more than 110 different mutations in the ZEB2 gene had been described. Nonsense mutations accounted for approximately 41% of the known punctual mutations and were localized mainly in exon 8. No obvious genotype-phenotype correlations had been observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17203459" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="genotypePhenotypeCorrelations" class="mim-anchor"></a>
|
|
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGenotypePhenotypeCorrelationsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The majority of ZEB2 mutations identified in patients with Mowat-Wilson syndrome lead to haploinsufficiency through premature termination or large gene deletions. In 3 unrelated patients with a mild form of MOWS, <a href="#7" class="mim-tip-reference" title="Ghoumid, J., Drevillon, L., Alavi-Naini, S. M., Bondurand, N., Rio, M., Briand-Suleau, A., Nasser, M., Goodwin, L., Raymond, P., Yanicostas, C., Goossens, M., Lyonnet, S., Mowat, D., Amiel, J., Soussi-Yanicostas, N., Giurgea, I. <strong>ZEB2 zinc-finger missense mutations lead to hypomorphic alleles and a mild Mowat-Wilson syndrome.</strong> Hum. Molec. Genet. 22: 2652-2661, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23466526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23466526</a>] [<a href="https://doi.org/10.1093/hmg/ddt114" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23466526">Ghoumid et al. (2013)</a> identified 3 different missense mutations in the ZEB2 gene (see, e.g., S1071P, <a href="#0016">605802.0016</a> and H1045R, <a href="#0017">605802.0017</a>). All 3 mutations occurred in the conserved C-terminal zinc finger cluster domain. In vitro functional expression studies showed that these 3 missense mutations lost the ability to bind to the E-cadherin (CDH1; <a href="/entry/192090">192090</a>) promoter and to repress transcription of this target gene, consistent with a loss of function and without a dominant-negative effect. However, these mutant mRNAs showed significant phenotypic rescue of morpholino knockout zebrafish embryos: complete rescue with S1071P (84%) and partial rescue with H1045R (55%), indicating that they are hypomorphic alleles; wildtype mRNA showed 81% rescue. The patients had mild facial gestalt of MOWS and moderate intellectual disability, but no microcephaly, heart defects, or HSCR. The variable embryonic rescue correlated with the severity of the patients' phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23466526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>To clarify the molecular mechanisms underlying the clinical features of Hirschsprung disease-mental retardation syndrome, <a href="#22" class="mim-tip-reference" title="Van de Putte, T., Maruhashi, M., Francis, A., Nelles, L., Kondoh, H., Huylebroeck, D., Higashi, Y. <strong>Mice lacking Zfhx1b, the gene that codes for Smad-interacting protein-1, reveal a role for multiple neural crest cell defects in the etiology of Hirschsprung disease-mental retardation syndrome.</strong> Am. J. Hum. Genet. 72: 465-470, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12522767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12522767</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12522767[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/346092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12522767">Van de Putte et al. (2003)</a> generated mice that carried a Zfhx1b mutation comparable to those found in several human patients. They showed that Zfhx1b knockout mice did not develop postotic vagal neural crest cells, the precursors of the enteric nervous system that is affected in patients with Hirschsprung disease, and displayed a delamination arrest of cranial neural crest cells, which form the skeletomuscular elements of the vertebral head. This suggests that the gene product is essential for the development of vagal neural crest precursors and the migratory behavior of cranial neural crest in the mouse. Furthermore, they showed that the gene product is involved in the specification of neuroepithelium. Sip1-knockout embryos died around embryonic day 9.5, with failed neural tube closure, lack of a sharp boundary between the neural plate and the rest of the ectoderm, and lack of the first branchial arch. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12522767" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Van de Putte, T., Francis, A., Nelles, L., van Grunsven, L. A., Huylebroeck, D. <strong>Neural crest-specific removal of Zfhx1b in mouse leads to a wide range of neurocristopathies reminiscent of Mowat-Wilson syndrome.</strong> Hum. Molec. Genet. 16: 1423-1436, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17478475/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17478475</a>] [<a href="https://doi.org/10.1093/hmg/ddm093" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17478475">Van de Putte et al. (2007)</a> found that conditional deletion of Zeb2 in mouse neural crest precursors was embryonic lethal. Mutant mice displayed craniofacial and gastrointestinal malformations similar to those of patients with Mowat-Wilson syndrome. In addition, mutant mice had defects in the heart, melanoblasts, and sympathetic and parasympathetic anlagen. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17478475" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 single layer of neuroepithelial cells lining the embryonic neural tube gives rise to the entire repertoire of neurons, astrocytes, and oligodendrocytes in the adult central nervous system. <a href="#20" class="mim-tip-reference" title="Seuntjens, E., Nityanandam, A., Miquelajauregui, A., Debruyn, J., Stryjewska, A., Goebbels, S., Nave, K.-A., Huylebroeck, D., Tarabykin, V. <strong>Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors.</strong> Nature Neurosci. 12: 1373-1380, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19838179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19838179</a>] [<a href="https://doi.org/10.1038/nn.2409" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19838179">Seuntjens et al. (2009)</a> found that conditional Sip1 deletion in young mouse neurons induced premature production of upper layer neurons at the expense of deep layers, precocious and increased generation of glial precursors, and elevated numbers of astrocytes at early postnatal stages. Microarray analysis showed that Ntf3 (<a href="/entry/162660">162660</a>) and Fgf9 (<a href="/entry/600921">600921</a>) were over- and prematurely expressed in mutant brains. In the absence of Sip1, there was also a premature peak of MAPK (see <a href="/entry/176948">176948</a>) signaling in neural progenitor cells. <a href="#20" class="mim-tip-reference" title="Seuntjens, E., Nityanandam, A., Miquelajauregui, A., Debruyn, J., Stryjewska, A., Goebbels, S., Nave, K.-A., Huylebroeck, D., Tarabykin, V. <strong>Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors.</strong> Nature Neurosci. 12: 1373-1380, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19838179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19838179</a>] [<a href="https://doi.org/10.1038/nn.2409" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19838179">Seuntjens et al. (2009)</a> concluded that SIP1 functions in the postmitotic compartment of the neocortex to control the expression of growth factor genes that feed back to progenitors to regulate production of the neurons and glial cells required for corticogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19838179" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Ghoumid, J., Drevillon, L., Alavi-Naini, S. M., Bondurand, N., Rio, M., Briand-Suleau, A., Nasser, M., Goodwin, L., Raymond, P., Yanicostas, C., Goossens, M., Lyonnet, S., Mowat, D., Amiel, J., Soussi-Yanicostas, N., Giurgea, I. <strong>ZEB2 zinc-finger missense mutations lead to hypomorphic alleles and a mild Mowat-Wilson syndrome.</strong> Hum. Molec. Genet. 22: 2652-2661, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23466526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23466526</a>] [<a href="https://doi.org/10.1093/hmg/ddt114" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23466526">Ghoumid et al. (2013)</a> found that morpholino knockout of the zebrafish Zeb2 ortholog sip1b in zebrafish embryos resulted in severe neurodevelopmental abnormalities, including small brains and defects of tectum development, as well as impaired neuronal crest cell migration with a lack of development of pharyngeal arches and jaw cartilages. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23466526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 insertional mutagenesis, <a href="#6" class="mim-tip-reference" title="El-Kasti, M. M., Wells, T., Carter, D. A. <strong>A novel long-range enhancer regulates postnatal expression of Zeb2: implications for Mowat-Wilson syndrome phenotypes.</strong> Hum. Molec. Genet. 21: 5429-5442, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001561</a>] [<a href="https://doi.org/10.1093/hmg/dds389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23001561">El-Kasti et al. (2012)</a> developed a line of transgenic rats that exhibited autosomal dominant postnatal lethality in males only. Female transgenic rats exhibited delayed development, but thrived and had normal life spans. Death in male transgenic rats was due to delayed renal development, leading to severe renal insufficiency. Southern blot and sequencing suggested that a head-to-tail concatamer of 2 copies of the transgene caused a 12-kb genomic deletion 1.2 Mb upstream of the Zeb2 gene. This region is syntenic to a 3.5-Mb region upstream of the human ZEB2 gene on chromosome 2q22.3. The Zeb2 coding region and transcript size were unaffected by the deletion, but Zeb2 expression in kidney was significantly reduced. Immunohistochemical analysis revealed reduced Zeb2 protein expression in neonatal transgenic rat kidney, but normal Zeb2 expression in brain. Microarray analysis revealed downregulation of androgen-related genes in both male and female transgenic mice, and male transgenic kidneys showed aberrant expression of genes involved in renal development and function. Using an in vitro transcription assay, <a href="#6" class="mim-tip-reference" title="El-Kasti, M. M., Wells, T., Carter, D. A. <strong>A novel long-range enhancer regulates postnatal expression of Zeb2: implications for Mowat-Wilson syndrome phenotypes.</strong> Hum. Molec. Genet. 21: 5429-5442, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001561</a>] [<a href="https://doi.org/10.1093/hmg/dds389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23001561">El-Kasti et al. (2012)</a> found that the deleted region in transgenic rats functioned as an enhancer for Zeb2 in both sequence orientations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23001561" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>17 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/605802" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=605802[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 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, ARG549TER
|
|
</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> rs137852980 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852980;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/rs137852980?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=rs137852980" 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=rs137852980" 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=RCV000005020" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005020" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005020</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Hirschsprung disease associated with microcephaly, mental retardation, hypertelorism, submucous cleft palate, and short stature (<a href="/entry/235730">235730</a>), <a href="#26" class="mim-tip-reference" title="Wakamatsu, N., Yamada, Y., Yamada, K., Ono, T., Nomura, N., Taniguchi, H., Kitoh, H., Mutoh, N., Yamanaka, T., Mushiake, K., Kato, K., Sonta, S., Nagaya, M. <strong>Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease.</strong> Nature Genet. 27: 369-370, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11279515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11279515</a>] [<a href="https://doi.org/10.1038/86860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11279515">Wakamatsu et al. (2001)</a> identified an A-to-T transversion at nucleotide 1645 of the SMADIP1 gene, resulting in an arg-to-ter substitution at codon 549 (R549X). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11279515" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, ARG695TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852981 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852981;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=rs137852981" 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=rs137852981" 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=RCV000005021 OR RCV000213082" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005021, RCV000213082" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005021...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Hirschsprung disease associated with microcephaly, mental retardation, hypertelorism, submucous cleft palate, and short stature (<a href="/entry/235730">235730</a>), <a href="#26" class="mim-tip-reference" title="Wakamatsu, N., Yamada, Y., Yamada, K., Ono, T., Nomura, N., Taniguchi, H., Kitoh, H., Mutoh, N., Yamanaka, T., Mushiake, K., Kato, K., Sonta, S., Nagaya, M. <strong>Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease.</strong> Nature Genet. 27: 369-370, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11279515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11279515</a>] [<a href="https://doi.org/10.1038/86860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11279515">Wakamatsu et al. (2001)</a> identified a C-to-T transition at nucleotide 2083 of the SMADIP1 gene, resulting in an arg-to-ter substitution at codon 695 (R695X). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11279515" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 6 patients with clinical features similar to those reported in patients with ZFHX1B mutations but without Hirschsprung disease, <a href="#27" class="mim-tip-reference" title="Yamada, K., Yamada, Y., Nomura, N., Miura, K., Wakako, R., Hayakawa, C., Matsumoto, A., Kumagai, T., Yoshimura, I., Miyazaki, S., Kato, K., Sonta, S., Ono, H., Yamanaka, T., Nagaya, M., Wakamatsu, N. <strong>Nonsense and frameshift mutations in ZFHX1B, encoding Smad-interacting protein 1, cause a complex developmental disorder with a great variety of clinical features.</strong> Am. J. Hum. Genet. 69: 1178-1185, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11592033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11592033</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11592033[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/324343" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11592033">Yamada et al. (2001)</a> found that 3 had the R695X mutation. Thus, Hirschsprung disease is not a consistent feature. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11592033" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, 4-BP DEL, NT1173
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776603 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776603;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=rs587776603" 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=rs587776603" 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=RCV000005022" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005022" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005022</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Hirschsprung disease associated with microcephaly and mental retardation, hypertelorism, submucous cleft palate, and short stature (<a href="/entry/235730">235730</a>), <a href="#26" class="mim-tip-reference" title="Wakamatsu, N., Yamada, Y., Yamada, K., Ono, T., Nomura, N., Taniguchi, H., Kitoh, H., Mutoh, N., Yamanaka, T., Mushiake, K., Kato, K., Sonta, S., Nagaya, M. <strong>Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease.</strong> Nature Genet. 27: 369-370, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11279515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11279515</a>] [<a href="https://doi.org/10.1038/86860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11279515">Wakamatsu et al. (2001)</a> identified a 4-bp deletion (AACA) at nucleotide 1173 of the SMADIP1 gene, resulting in a frameshift at codon 392 leading to a termination codon at amino acid residue 394 in exon 8. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11279515" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, 1-BP INS, 1421A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776604 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776604;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=rs587776604" 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=rs587776604" 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=RCV000005023 OR RCV000498048 OR RCV002390091" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005023, RCV000498048, RCV002390091" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005023...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Hirschsprung disease associated with microcephaly and mental retardation, hypertelorism, submucous cleft palate, and short stature (<a href="/entry/235730">235730</a>) originally reported by <a href="#14" class="mim-tip-reference" title="Mowat, D. R., Croaker, G. D. H., Cass, D. T., Kerr, B. A., Chaitow, J., Ades, L. C., Chia, N. L., Wilson, M. J. <strong>Hirschsprung disease, microcephaly, mental retardation, and characteristic facial features: delineation of a new syndrome and identification of a locus at chromosome 2q22-q23.</strong> J. Med. Genet. 35: 617-623, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9719364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9719364</a>] [<a href="https://doi.org/10.1136/jmg.35.8.617" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9719364">Mowat et al. (1998)</a>, <a href="#3" class="mim-tip-reference" title="Cacheux, V., Dastot-Le Moal, F., Kaariainen, H., Bondurand, N., Rintala, R., Boissier, B., Wilson, M., Mowat, D., Goossens, M. <strong>Loss-of-function mutations in SIP1 Smad interacting protein 1 result in a syndromic Hirschsprung disease.</strong> Hum. Molec. Genet. 10: 1503-1510, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11448942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11448942</a>] [<a href="https://doi.org/10.1093/hmg/10.14.1503" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11448942">Cacheux et al. (2001)</a> identified insertion of an adenine residue following nucleotide 1421 of the SMADIP1 gene, resulting in a frameshift and leading to a termination codon at amino acid residue 481 in exon 8. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11448942+9719364" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, 2-BP INS, 760CA
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776605 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776605;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=rs587776605" 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=rs587776605" 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=RCV000005024" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005024" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005024</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 25-year-old male patient with many features of the Hirschsprung disease-mental retardation syndrome but without Hirschsprung disease (<a href="/entry/235730">235730</a>), <a href="#27" class="mim-tip-reference" title="Yamada, K., Yamada, Y., Nomura, N., Miura, K., Wakako, R., Hayakawa, C., Matsumoto, A., Kumagai, T., Yoshimura, I., Miyazaki, S., Kato, K., Sonta, S., Ono, H., Yamanaka, T., Nagaya, M., Wakamatsu, N. <strong>Nonsense and frameshift mutations in ZFHX1B, encoding Smad-interacting protein 1, cause a complex developmental disorder with a great variety of clinical features.</strong> Am. J. Hum. Genet. 69: 1178-1185, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11592033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11592033</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11592033[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/324343" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11592033">Yamada et al. (2001)</a> found a 2-bp insertion (760insCA) in the ZFHX1B gene. The patient showed hypertelorism and microcephaly (head circumference 2 standard deviations below the mean) at birth. He developed epilepsy at age 1 year. He showed delayed motor development, with neck control developing at age 8 months and walking without support at age 2 years. He was severely mentally retarded, with only a few words of speech. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11592033" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, 1-BP INS, 2453T
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776606 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776606;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=rs587776606" 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=rs587776606" 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=RCV000005025" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005025" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005025</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Hirschsprung disease-mental retardation syndrome (<a href="/entry/235730">235730</a>), <a href="#1" class="mim-tip-reference" title="Amiel, J., Espinosa-Parrilla, Y., Steffann, J., Gosset, P., Pelet, A., Prieur, M., Boute, O., Choiset, A., Lacombe, D., Philip, N., Le Merrer, M., Tanaka, H., Till, M., Touraine, R., Toutain, A., Vekemans, M., Munnich, A., Lyonnet, S. <strong>Large-scale deletions and SMADIP1 truncating mutations in syndromic Hirschsprung disease with involvement of midline structures.</strong> Am. J. Hum. Genet. 69: 1370-1377, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11595972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11595972</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11595972[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/324342" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11595972">Amiel et al. (2001)</a> found a 1-bp insertion (2453insT) in the ZFHX1B gene. The patient had the characteristic facies, with sunken eyes, downslanting palpebral fissures, strabismus, thick eyebrows with lateral flaring, saddle nose, pointed chin, thick antehelix, and rotated ears with uplifted, fleshy earlobes. The patient did not have agenesis of the corpus callosum but did have hydronephrosis as well as heart defects: atrial septal defects, ventricular septal defects, and pulmonic stenosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11595972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, 1-BP DEL, 1892A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776607 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776607;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=rs587776607" 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=rs587776607" 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=RCV000005026" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005026" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005026</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Hirschsprung disease-mental retardation syndrome (<a href="/entry/235730">235730</a>), <a href="#29" class="mim-tip-reference" title="Zweier, C., Albrecht, B., Mitulla, B., Behrens, R., Beese, M., Gillessen-Kaesbach, G., Rott, H.-D., Rauch, A. <strong>'Mowat-Wilson' syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.</strong> Am. J. Med. Genet. 108: 177-181, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891681</a>]" pmid="11891681">Zweier et al. (2002)</a> found a heterozygous 1-bp deletion (1892delA) in exon 8 of the ZFHX1B gene, resulting in a premature stop codon after 14 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11891681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, 2-BP INS, 553TG
|
|
</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> rs587776608 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776608;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/rs587776608?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=rs587776608" 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=rs587776608" 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=RCV000005027" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005027" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005027</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with many features of the Hirschsprung disease-mental retardation syndrome (<a href="/entry/235730">235730</a>) but without Hirschsprung disease, <a href="#29" class="mim-tip-reference" title="Zweier, C., Albrecht, B., Mitulla, B., Behrens, R., Beese, M., Gillessen-Kaesbach, G., Rott, H.-D., Rauch, A. <strong>'Mowat-Wilson' syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.</strong> Am. J. Med. Genet. 108: 177-181, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891681</a>]" pmid="11891681">Zweier et al. (2002)</a> found a heterozygous 2-bp insertion in exon 5 in the ZFHX1B gene, leading to a stop codon after 27 amino acids. To investigate if this truncating mutation led to mRNA decay, <a href="#29" class="mim-tip-reference" title="Zweier, C., Albrecht, B., Mitulla, B., Behrens, R., Beese, M., Gillessen-Kaesbach, G., Rott, H.-D., Rauch, A. <strong>'Mowat-Wilson' syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.</strong> Am. J. Med. Genet. 108: 177-181, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891681</a>]" pmid="11891681">Zweier et al. (2002)</a> performed RT-PCR of mRNA from the patient's peripheral blood and found the mutated transcript. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11891681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, SER852TER
|
|
</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> rs137852982 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852982;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/rs137852982?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=rs137852982" 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=rs137852982" 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=RCV000005028" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005028" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005028</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with many features of the Hirschsprung disease-mental retardation syndrome (<a href="/entry/235730">235730</a>) but without Hirschsprung disease, <a href="#29" class="mim-tip-reference" title="Zweier, C., Albrecht, B., Mitulla, B., Behrens, R., Beese, M., Gillessen-Kaesbach, G., Rott, H.-D., Rauch, A. <strong>'Mowat-Wilson' syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.</strong> Am. J. Med. Genet. 108: 177-181, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891681</a>]" pmid="11891681">Zweier et al. (2002)</a> found a heterozygous C-to-G substitution in exon 8 of the ZFHX1B gene, resulting in a ser852-to-ter substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11891681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, 2-BP INS, 3567CC
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776609 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776609;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=rs587776609" 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=rs587776609" 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=RCV000005029" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005029" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005029</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Hirschsprung disease-mental retardation syndrome (<a href="/entry/235730">235730</a>), <a href="#29" class="mim-tip-reference" title="Zweier, C., Albrecht, B., Mitulla, B., Behrens, R., Beese, M., Gillessen-Kaesbach, G., Rott, H.-D., Rauch, A. <strong>'Mowat-Wilson' syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.</strong> Am. J. Med. Genet. 108: 177-181, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891681</a>]" pmid="11891681">Zweier et al. (2002)</a> found a heterozygous 2-bp insertion (3567insCC) in exon 10, resulting in a frameshift and an enlarged protein of 1,241 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11891681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 HIRSCHSPRUNG DISEASE-MENTAL RETARDATION SYNDROME, LATE INFANTILE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, 3-BP DEL, 295AAC
|
|
</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> rs587776610 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776610;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/rs587776610?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=rs587776610" 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=rs587776610" 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=RCV000005030 OR RCV000490485" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005030, RCV000490485" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005030...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#28" class="mim-tip-reference" title="Yoneda, M., Fujita, T., Yamada, Y., Yamada, K., Fujii, A., Inagaki, T., Nakagawa, H., Shimada, A., Kishikawa, M., Nagaya, M., Azuma, T., Kuriyama, M., Wakamatsu, N. <strong>Late infantile Hirschsprung disease-mental retardation syndrome with a 3-bp deletion in ZFHX1B.</strong> Neurology 59: 1637-1640, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12451214/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12451214</a>] [<a href="https://doi.org/10.1212/01.wnl.0000034842.78350.4e" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12451214">Yoneda et al. (2002)</a> reported a 48-year-old woman with late infantile-onset mental retardation who developed megacolon. Although the patient had no typical clinical features of Hirschsprung disease-mental retardation syndrome (<a href="/entry/235730">235730</a>), a 3-bp deletion eliminating asn99 was identified in exon 3 of the ZFHX1B gene. The woman was born of nonconsanguineous parents. She was noted to have mental retardation but received a full education in elementary school. She sometimes had constipation but did not require medication until age 48 years, when she presented with severe constipation and was found to have megacolon. This patient would appear to represent an intermediate stage between the full-blown Hirschsprung disease-mental retardation syndrome and Hirschsprung disease-mental retardation syndrome without Hirschsprung disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12451214" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, 300-KB DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000005031" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005031" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005031</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with typical features of Mowat-Wilson syndrome (<a href="/entry/235730">235730</a>), <a href="#31" class="mim-tip-reference" title="Zweier, C., Temple, I. K., Beemer, F., Zackai, E., Lerman-Sagie, T., Weschke, B., Anderson, C. E., Rauch, A. <strong>Characterisation of deletions of the ZFHX1B region and genotype-phenotype analysis in Mowat-Wilson syndrome.</strong> J. Med. Genet. 40: 601-605, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12920073/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12920073</a>] [<a href="https://doi.org/10.1136/jmg.40.8.601" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12920073">Zweier et al. (2003)</a> described a deletion of approximately 300 kb on chromosome 2q22, encompassing the ZFHX1B gene, as defined by FISH and marker analysis. The patient was pictured at age 10 years with a facial gestalt typical of Mowat-Wilson syndrome. Birth weight and length were at the 90th centile. He had ventricular septal defect and pulmonary stenosis. He was described as being affectionate and happy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12920073" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, 1-BP DEL, 1862T
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776611 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776611;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=rs587776611" 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=rs587776611" 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=RCV000005032" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005032" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005032</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a sister and brother with Mowat-Wilson syndrome (<a href="/entry/235730">235730</a>), <a href="#13" class="mim-tip-reference" title="McGaughran, J., Sinnott, S., Dastot-Le Moal, F., Wilson, M., Mowat, D., Sutton, B., Goossens, M. <strong>Recurrence of Mowat-Wilson syndrome in siblings with the same proven mutation.</strong> Am. J. Med. Genet. 137A: 302-304, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16088920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16088920</a>] [<a href="https://doi.org/10.1002/ajmg.a.30896" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16088920">McGaughran et al. (2005)</a> identified heterozygosity for a 1-bp deletion (1862delT) in exon 8 of the ZFHX1B gene, resulting in a stop codon at position 645 and predicting a truncated protein missing the homeodomain and the C-terminal zinc finger domain. The mutation was not found in the unaffected parents' lymphocyte-derived DNA, suggesting germline mosaicism in the sibs. <a href="#13" class="mim-tip-reference" title="McGaughran, J., Sinnott, S., Dastot-Le Moal, F., Wilson, M., Mowat, D., Sutton, B., Goossens, M. <strong>Recurrence of Mowat-Wilson syndrome in siblings with the same proven mutation.</strong> Am. J. Med. Genet. 137A: 302-304, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16088920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16088920</a>] [<a href="https://doi.org/10.1002/ajmg.a.30896" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16088920">McGaughran et al. (2005)</a> stated that this was the first report of a sib recurrence of Mowat-Wilson syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16088920" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, IVS1AS, 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">rs587776612 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776612;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=rs587776612" 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=rs587776612" 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=RCV000005033" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005033" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005033</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 5-year-old boy with a facial gestalt of Mowat-Wilson syndrome (<a href="/entry/235730">235730</a>) and an unusually mild phenotype, <a href="#30" class="mim-tip-reference" title="Zweier, C., Horn, D., Kraus, C., Rauch, A. <strong>Atypical ZFHX1B mutation associated with a mild Mowat-Wilson syndrome phenotype.</strong> Am. J. Med. Genet. 140A: 869-872, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16532472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16532472</a>] [<a href="https://doi.org/10.1002/ajmg.a.31196" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16532472">Zweier et al. (2006)</a> identified heterozygosity for a G-to-A transition at the -1 position in the splice acceptor site of exon 2 of the ZFHX1B gene (alternatively, -70G-A), predicted to result in skipping of exon 2 including the start codon. The aberrant transcript contains an alternative upstream start codon, resulting in a mutant protein differing only for the first 24 amino acids from the wildtype protein. The mutation was excluded in both parents, revealing its de novo origin. The patient's facial gestalt was less striking than the majority of MWS patients, and his psychomotor development was much better than expected in classic MWS. Except for increased disposition for seizures on EEG and body measurements at the 3rd centile, he showed no other anomalies frequently observed in MWS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16532472" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Verstappen, G., van Grunsven, L. A., Michiels, C., Van de Putte, T., Souopgui, J., Van Damme, J., Bellefroid, E., Vandekerckhove, J., Huylebroeck, D. <strong>Atypical Mowat-Wilson patient confirms the importance of the novel association between ZFHX1B/SIP1 and NuRD corepressor complex.</strong> Hum. Molec. Genet. 17: 1175-1183, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18182442/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18182442</a>] [<a href="https://doi.org/10.1093/hmg/ddn007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18182442">Verstappen et al. (2008)</a> showed the protein resulting from the -70G-A mutation was unable to interact with the NURD complex, which plays a key role in transcriptional repression, as well as decreased transcriptional repression of Bmp4 (<a href="/entry/112262">112262</a>). The findings were important because they demonstrated the effect of aberrant function of a single domain of the ZEB2 protein, which resulted in a relatively milder phenotype compared to complete haploinsufficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18182442" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, GLN1119ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852983 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852983;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=rs137852983" 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=rs137852983" 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=RCV000005034" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005034" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005034</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2.5-year-old boy with the overall facial phenotype of Mowat-Wilson syndrome (<a href="/entry/235730">235730</a>) but with cleft lip and palate and lacking the characteristic eyebrows, <a href="#8" class="mim-tip-reference" title="Heinritz, W., Zweier, C., Froster, U. G., Strenge, S., Kujat, A., Syrbe, S., Rauch, A., Schuster, V. <strong>A missense mutation in the ZFHX1B gene associated with an atypical Mowat-Wilson syndrome phenotype.</strong> Am. J. Med. Genet. 140A: 1223-1227, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16688751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16688751</a>] [<a href="https://doi.org/10.1002/ajmg.a.31267" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16688751">Heinritz et al. (2006)</a> identified heterozygosity for a de novo 3356A-G transition in exon 10 of the ZFHX1B gene, resulting in a gln1119-to-arg (Q1119R) substitution. The patient also had brachytelephalangy, which the authors stated had never been described before in Mowat-Wilson syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16688751" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, SER1071PRO
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397515448 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515448;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=rs397515448" 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=rs397515448" 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=RCV000050218 OR RCV002513706" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000050218, RCV002513706" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000050218...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with a relatively mild form of Mowat-Wilson syndrome (<a href="/entry/235730">235730</a>), <a href="#7" class="mim-tip-reference" title="Ghoumid, J., Drevillon, L., Alavi-Naini, S. M., Bondurand, N., Rio, M., Briand-Suleau, A., Nasser, M., Goodwin, L., Raymond, P., Yanicostas, C., Goossens, M., Lyonnet, S., Mowat, D., Amiel, J., Soussi-Yanicostas, N., Giurgea, I. <strong>ZEB2 zinc-finger missense mutations lead to hypomorphic alleles and a mild Mowat-Wilson syndrome.</strong> Hum. Molec. Genet. 22: 2652-2661, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23466526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23466526</a>] [<a href="https://doi.org/10.1093/hmg/ddt114" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23466526">Ghoumid et al. (2013)</a> identified a heterozygous c.3211T-C transition in the ZEB2 gene, resulting in a ser1071-to-pro (S1071P) substitution at a highly conserved residue in the C-terminal zinc finger domain. The mutation was not present in the mother, in 200 control chromosomes, or in SNP databases; DNA from the father was not available. In vitro functional expression studies showed that the mutant protein lost the ability to bind to the E-cadherin (CDH1; <a href="/entry/192090">192090</a>) promoter and to repress transcription of this target gene, consistent with a loss of function and without a dominant-negative effect. However, this mutant mRNA showed complete phenotypic rescue of morpholino knockout zebrafish embryos, indicating that it is a hypomorphic allele. The patient had the typical facial gestalt of the disorder, moderate intellectual disability, delayed walking, and seizures, but no microcephaly and no cardiac or gastrointestinal abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23466526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
ZEB2, HIS1045ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397515449 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397515449;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=rs397515449" 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=rs397515449" 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=RCV000050219" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000050219" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000050219</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with a relatively mild form of Mowat-Wilson syndrome (<a href="/entry/235730">235730</a>), <a href="#7" class="mim-tip-reference" title="Ghoumid, J., Drevillon, L., Alavi-Naini, S. M., Bondurand, N., Rio, M., Briand-Suleau, A., Nasser, M., Goodwin, L., Raymond, P., Yanicostas, C., Goossens, M., Lyonnet, S., Mowat, D., Amiel, J., Soussi-Yanicostas, N., Giurgea, I. <strong>ZEB2 zinc-finger missense mutations lead to hypomorphic alleles and a mild Mowat-Wilson syndrome.</strong> Hum. Molec. Genet. 22: 2652-2661, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23466526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23466526</a>] [<a href="https://doi.org/10.1093/hmg/ddt114" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23466526">Ghoumid et al. (2013)</a> identified a heterozygous de novo c.3134A-G transition in the ZEB2 gene, resulting in a his1045-to-arg (H1045R) substitution at a highly conserved residue in the C-terminal zinc finger domain. The mutation was not present in 200 control chromosomes or in SNP databases. In vitro functional expression studies showed that the mutant protein lost the ability to bind to the E-cadherin (CDH1; <a href="/entry/192090">192090</a>) promoter and to repress transcription of this target gene, consistent with a loss of function and without a dominant-negative effect. However, this mutant mRNA showed 53% phenotypic rescue of morpholino knockout zebrafish embryos, indicating that it is a hypomorphic allele. The patient had a mild facial gestalt of the disorder, moderate intellectual disability, delayed walking, hippocampal abnormalities, frontal cortical atrophy, and hypospadias, but no microcephaly and no cardiac or gastrointestinal abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23466526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#Postigo2000" class="mim-tip-reference" title="Postigo, A. A., Dean, D. C. <strong>Differential expression and function of members of the zfh-1 family of zinc finger/homeodomain repressors.</strong> Proc. Nat. Acad. Sci. 97: 6391-6396, 2000.">Postigo and Dean (2000)</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="Amiel2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Amiel, J., Espinosa-Parrilla, Y., Steffann, J., Gosset, P., Pelet, A., Prieur, M., Boute, O., Choiset, A., Lacombe, D., Philip, N., Le Merrer, M., Tanaka, H., Till, M., Touraine, R., Toutain, A., Vekemans, M., Munnich, A., Lyonnet, S.
|
|
<strong>Large-scale deletions and SMADIP1 truncating mutations in syndromic Hirschsprung disease with involvement of midline structures.</strong>
|
|
Am. J. Hum. Genet. 69: 1370-1377, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11595972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11595972</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11595972[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=11595972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/324342" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Beltran2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Beltran, M., Puig, I., Pena, C., Garcia, J. M., Alvarez, A. B., Pena, R., Bonilla, F., Garcia de Herreros, A.
|
|
<strong>A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition.</strong>
|
|
Genes Dev. 22: 756-769, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18347095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18347095</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18347095[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=18347095" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1101/gad.455708" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Cacheux2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cacheux, V., Dastot-Le Moal, F., Kaariainen, H., Bondurand, N., Rintala, R., Boissier, B., Wilson, M., Mowat, D., Goossens, M.
|
|
<strong>Loss-of-function mutations in SIP1 Smad interacting protein 1 result in a syndromic Hirschsprung disease.</strong>
|
|
Hum. Molec. Genet. 10: 1503-1510, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11448942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11448942</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11448942" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/10.14.1503" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Comijn2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Comijn, J., Berx, G., Vermassen, P., Verschueren, K., van Grunsven, L., Bruyneel, E., Mareel, M., Huylebroeck, D., van Roy, F.
|
|
<strong>The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion.</strong>
|
|
Molec. Cell 7: 1267-1278, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11430829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11430829</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11430829" target="_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(01)00260-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Dastot-Le Moal2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dastot-Le Moal, F., Wilson, M., Mowat, D., Collot, N., Niel, F., Goossens, M.
|
|
<strong>ZFHX1B mutations in patients with Mowat-Wilson syndrome.</strong>
|
|
Hum. Mutat. 28: 313-321, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17203459/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17203459</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17203459" target="_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.20452" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="El-Kasti2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
El-Kasti, M. M., Wells, T., Carter, D. A.
|
|
<strong>A novel long-range enhancer regulates postnatal expression of Zeb2: implications for Mowat-Wilson syndrome phenotypes.</strong>
|
|
Hum. Molec. Genet. 21: 5429-5442, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23001561/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23001561</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23001561" target="_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/dds389" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Ghoumid2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ghoumid, J., Drevillon, L., Alavi-Naini, S. M., Bondurand, N., Rio, M., Briand-Suleau, A., Nasser, M., Goodwin, L., Raymond, P., Yanicostas, C., Goossens, M., Lyonnet, S., Mowat, D., Amiel, J., Soussi-Yanicostas, N., Giurgea, I.
|
|
<strong>ZEB2 zinc-finger missense mutations lead to hypomorphic alleles and a mild Mowat-Wilson syndrome.</strong>
|
|
Hum. Molec. Genet. 22: 2652-2661, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23466526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23466526</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23466526" target="_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/ddt114" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Heinritz2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Heinritz, W., Zweier, C., Froster, U. G., Strenge, S., Kujat, A., Syrbe, S., Rauch, A., Schuster, V.
|
|
<strong>A missense mutation in the ZFHX1B gene associated with an atypical Mowat-Wilson syndrome phenotype.</strong>
|
|
Am. J. Med. Genet. 140A: 1223-1227, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16688751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16688751</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16688751" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.31267" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Ishihara2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ishihara, N., Yamada, K., Yamada, Y., Miura, K., Kato, J., Kuwabara, N., Hara, Y., Kobayashi, Y., Hoshino, K., Nomura, Y., Mimaki, M., Ohya, K., and 16 others.
|
|
<strong>Clinical and molecular analysis of Mowat-Wilson syndrome associated with ZFHX1B mutations and deletions at 2q22-q24.1. (Letter)</strong>
|
|
J. Med. Genet. 41: 387-393, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15121779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15121779</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15121779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2003.016154" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Kato2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kato, M., Zhang, J., Wang, M., Lanting, L., Yuan, H., Rossi, J. J., Natarajan, R.
|
|
<strong>MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 3432-3437, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360662</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360662[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=17360662" target="_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.0611192104" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Lin2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lin, S.-Y., Elledge, S. J.
|
|
<strong>Multiple tumor suppressor pathways negatively regulate telomerase.</strong>
|
|
Cell 113: 881-889, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12837246/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12837246</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12837246" target="_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(03)00430-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Liu2022" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Liu, T.-T., Kim, S., Desai, P., Kim, D.-H., Huang, X., Ferris, S. T., Wu, R., Ou, F., Egawa, T., Van Dyken, S. J., Diamond, M. S., Johnson, P. F., Kubo, M., Murphy, T. L., Murphy, K. M.
|
|
<strong>Ablation of cDC2 development by triple mutations within the Zeb2 enhancer.</strong>
|
|
Nature 607: 142-148, 2022.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35732734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35732734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35732734[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=35732734" target="_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/s41586-022-04866-z" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="McGaughran2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McGaughran, J., Sinnott, S., Dastot-Le Moal, F., Wilson, M., Mowat, D., Sutton, B., Goossens, M.
|
|
<strong>Recurrence of Mowat-Wilson syndrome in siblings with the same proven mutation.</strong>
|
|
Am. J. Med. Genet. 137A: 302-304, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16088920/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16088920</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16088920" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.30896" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Mowat1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mowat, D. R., Croaker, G. D. H., Cass, D. T., Kerr, B. A., Chaitow, J., Ades, L. C., Chia, N. L., Wilson, M. J.
|
|
<strong>Hirschsprung disease, microcephaly, mental retardation, and characteristic facial features: delineation of a new syndrome and identification of a locus at chromosome 2q22-q23.</strong>
|
|
J. Med. Genet. 35: 617-623, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9719364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9719364</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9719364" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.35.8.617" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Nagase1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nagase, T., Ishikawa, K., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O.
|
|
<strong>Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.</strong>
|
|
DNA Res. 5: 31-39, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9628581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9628581</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9628581" target="_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/dnares/5.1.31" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Park2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Park, S.-M., Gaur, A. B., Lengyel, E., Peter, M. E.
|
|
<strong>The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2.</strong>
|
|
Genes Dev. 22: 894-907, 2008. Note: Erratum: Genes Dev. 23: 1378 only, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18381893/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18381893</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18381893[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=18381893" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1101/gad.1640608" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Postigo2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Postigo, A. A., Dean, D. C.
|
|
<strong>Differential expression and function of members of the zfh-1 family of zinc finger/homeodomain repressors.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 6391-6396, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10841546/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10841546</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10841546[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=10841546" target="_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.97.12.6391" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Remacle1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Remacle, J. E., Kraft, H., Lerchner, W., Wuytens, G., Collart, C., Verschueren, K., Smith, J. C., Huylebroeck, D.
|
|
<strong>New mode of DNA binding of multi-zinc finger transcription factors: deltaEF1 family members bind with two hands to two target sites.</strong>
|
|
EMBO J. 18: 5073-5084, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10487759/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10487759</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10487759" target="_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/emboj/18.18.5073" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Renthal2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Renthal, N. E., Chen, C.-C., Williams. K. C., Gerard, R. D., Prange-Kiel, J., Mendelson, C. R.
|
|
<strong>miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor.</strong>
|
|
Proc. Nat. Acad. Sci. 107: 20828-20833, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21079000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21079000</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21079000[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=21079000" target="_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.1008301107" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Seuntjens2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Seuntjens, E., Nityanandam, A., Miquelajauregui, A., Debruyn, J., Stryjewska, A., Goebbels, S., Nave, K.-A., Huylebroeck, D., Tarabykin, V.
|
|
<strong>Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors.</strong>
|
|
Nature Neurosci. 12: 1373-1380, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19838179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19838179</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19838179" target="_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/nn.2409" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Van de Putte2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Van de Putte, T., Francis, A., Nelles, L., van Grunsven, L. A., Huylebroeck, D.
|
|
<strong>Neural crest-specific removal of Zfhx1b in mouse leads to a wide range of neurocristopathies reminiscent of Mowat-Wilson syndrome.</strong>
|
|
Hum. Molec. Genet. 16: 1423-1436, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17478475/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17478475</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17478475" target="_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/ddm093" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Van de Putte2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Van de Putte, T., Maruhashi, M., Francis, A., Nelles, L., Kondoh, H., Huylebroeck, D., Higashi, Y.
|
|
<strong>Mice lacking Zfhx1b, the gene that codes for Smad-interacting protein-1, reveal a role for multiple neural crest cell defects in the etiology of Hirschsprung disease-mental retardation syndrome.</strong>
|
|
Am. J. Hum. Genet. 72: 465-470, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12522767/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12522767</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12522767[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=12522767" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/346092" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Vandewalle2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vandewalle, C., Comijn, J., De Craene, B., Vermassen, P., Bruyneel, E., Andersen, H., Tulchinsky, E., Van Roy, F., Berx, G.
|
|
<strong>SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions.</strong>
|
|
Nucleic Acids Res. 33: 6566-6578, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16314317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16314317</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16314317[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=16314317" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/nar/gki965" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Verschueren1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Verschueren, K., Remacle, J. E., Collart, C., Kraft, H., Baker, B. S., Tylzanowski, P., Nelles, L., Wuytens, G., Su, M.-T., Bodmer, R., Smith, J. C., Huylebroeck, D.
|
|
<strong>SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5-prime-CACCT sequences in candidate target genes.</strong>
|
|
J. Biol. Chem. 274: 20489-20498, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10400677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10400677</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10400677" target="_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.274.29.20489" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Verstappen2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Verstappen, G., van Grunsven, L. A., Michiels, C., Van de Putte, T., Souopgui, J., Van Damme, J., Bellefroid, E., Vandekerckhove, J., Huylebroeck, D.
|
|
<strong>Atypical Mowat-Wilson patient confirms the importance of the novel association between ZFHX1B/SIP1 and NuRD corepressor complex.</strong>
|
|
Hum. Molec. Genet. 17: 1175-1183, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18182442/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18182442</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18182442" target="_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/ddn007" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Wakamatsu2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wakamatsu, N., Yamada, Y., Yamada, K., Ono, T., Nomura, N., Taniguchi, H., Kitoh, H., Mutoh, N., Yamanaka, T., Mushiake, K., Kato, K., Sonta, S., Nagaya, M.
|
|
<strong>Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease.</strong>
|
|
Nature Genet. 27: 369-370, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11279515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11279515</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11279515" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/86860" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Yamada2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yamada, K., Yamada, Y., Nomura, N., Miura, K., Wakako, R., Hayakawa, C., Matsumoto, A., Kumagai, T., Yoshimura, I., Miyazaki, S., Kato, K., Sonta, S., Ono, H., Yamanaka, T., Nagaya, M., Wakamatsu, N.
|
|
<strong>Nonsense and frameshift mutations in ZFHX1B, encoding Smad-interacting protein 1, cause a complex developmental disorder with a great variety of clinical features.</strong>
|
|
Am. J. Hum. Genet. 69: 1178-1185, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11592033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11592033</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11592033[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=11592033" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/324343" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Yoneda2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yoneda, M., Fujita, T., Yamada, Y., Yamada, K., Fujii, A., Inagaki, T., Nakagawa, H., Shimada, A., Kishikawa, M., Nagaya, M., Azuma, T., Kuriyama, M., Wakamatsu, N.
|
|
<strong>Late infantile Hirschsprung disease-mental retardation syndrome with a 3-bp deletion in ZFHX1B.</strong>
|
|
Neurology 59: 1637-1640, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12451214/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12451214</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12451214" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/01.wnl.0000034842.78350.4e" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Zweier2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zweier, C., Albrecht, B., Mitulla, B., Behrens, R., Beese, M., Gillessen-Kaesbach, G., Rott, H.-D., Rauch, A.
|
|
<strong>'Mowat-Wilson' syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.</strong>
|
|
Am. J. Med. Genet. 108: 177-181, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11891681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11891681</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11891681" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Zweier2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zweier, C., Horn, D., Kraus, C., Rauch, A.
|
|
<strong>Atypical ZFHX1B mutation associated with a mild Mowat-Wilson syndrome phenotype.</strong>
|
|
Am. J. Med. Genet. 140A: 869-872, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16532472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16532472</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16532472" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.31196" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Zweier2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zweier, C., Temple, I. K., Beemer, F., Zackai, E., Lerman-Sagie, T., Weschke, B., Anderson, C. E., Rauch, A.
|
|
<strong>Characterisation of deletions of the ZFHX1B region and genotype-phenotype analysis in Mowat-Wilson syndrome.</strong>
|
|
J. Med. Genet. 40: 601-605, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12920073/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12920073</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12920073" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.40.8.601" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Bao Lige - updated : 01/05/2024
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Patricia A. Hartz - updated : 12/13/2013<br>Cassandra L. Kniffin - updated : 7/24/2013<br>Cassandra L. Kniffin - updated : 3/21/2011<br>Patricia A. Hartz - updated : 3/18/2010<br>Patricia A. Hartz - updated : 12/8/2009<br>Cassandra L. Kniffin - updated : 10/29/2009<br>Patricia A. Hartz - updated : 5/30/2008<br>Patricia A. Hartz - updated : 4/29/2008<br>Cassandra L. Kniffin - updated : 5/29/2007<br>Patricia A. Hartz - updated : 4/18/2007<br>Marla J. F. O'Neill - updated : 10/11/2006<br>Marla J. F. O'Neill - updated : 8/11/2006<br>Marla J. F. O'Neill - updated : 10/3/2005<br>Stylianos E. Antonarakis - updated : 11/24/2004<br>Marla J. F. O'Neill - updated : 6/11/2004<br>Victor A. McKusick - updated : 10/1/2003<br>Victor A. McKusick - updated : 2/27/2003<br>Victor A. McKusick - updated : 1/22/2003<br>Deborah L. Stone - updated : 4/25/2002<br>George E. Tiller - updated : 12/12/2001
|
|
</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">
|
|
Ada Hamosh : 3/29/2001
|
|
</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 : 02/17/2025
|
|
</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">
|
|
mgross : 01/05/2024<br>alopez : 07/02/2018<br>mgross : 12/17/2013<br>mcolton : 12/13/2013<br>carol : 9/13/2013<br>carol : 7/24/2013<br>ckniffin : 7/24/2013<br>mgross : 5/22/2013<br>alopez : 11/26/2012<br>terry : 4/26/2011<br>wwang : 3/25/2011<br>ckniffin : 3/21/2011<br>mgross : 3/22/2010<br>terry : 3/18/2010<br>mgross : 1/25/2010<br>terry : 12/8/2009<br>wwang : 12/2/2009<br>ckniffin : 10/29/2009<br>wwang : 11/24/2008<br>joanna : 8/27/2008<br>mgross : 5/30/2008<br>mgross : 4/29/2008<br>wwang : 6/11/2007<br>ckniffin : 5/29/2007<br>mgross : 4/18/2007<br>mgross : 4/18/2007<br>mgross : 4/18/2007<br>wwang : 10/13/2006<br>terry : 10/11/2006<br>wwang : 8/29/2006<br>wwang : 8/17/2006<br>terry : 8/11/2006<br>wwang : 10/10/2005<br>terry : 10/3/2005<br>mgross : 3/9/2005<br>mgross : 11/24/2004<br>tkritzer : 6/25/2004<br>carol : 6/14/2004<br>terry : 6/11/2004<br>terry : 3/18/2004<br>tkritzer : 10/21/2003<br>tkritzer : 10/6/2003<br>tkritzer : 10/1/2003<br>tkritzer : 5/19/2003<br>tkritzer : 2/28/2003<br>terry : 2/27/2003<br>cwells : 1/29/2003<br>tkritzer : 1/22/2003<br>carol : 4/25/2002<br>terry : 4/25/2002<br>alopez : 1/11/2002<br>cwells : 1/10/2002<br>terry : 12/20/2001<br>cwells : 12/18/2001<br>cwells : 12/14/2001<br>cwells : 12/14/2001<br>cwells : 12/12/2001<br>mgross : 10/31/2001<br>alopez : 4/13/2001<br>alopez : 4/2/2001<br>alopez : 3/29/2001
|
|
</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> 605802
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
ZINC FINGER E BOX-BINDING HOMEOBOX 2; ZEB2
|
|
|
|
</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">
|
|
ZINC FINGER HOMEOBOX 1B; ZFHX1B<br />
|
|
SMAD-INTERACTING PROTEIN 1; SMADIP1<br />
|
|
SIP1<br />
|
|
KIAA0569
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: ZEB2</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 703535000;
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 2q22.3
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 2:144,384,081-144,520,119 </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="1">
|
|
<span class="mim-font">
|
|
2q22.3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Mowat-Wilson syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
235730
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The ZEB2 gene is a member of the ZEB1 (189909)/Drosophila Zfh1 family of 2-handed zinc finger/homeodomain proteins and functions as a DNA-binding transcriptional repressor that interacts with activated SMADs (see 601595), the transducers of TGF-beta (190180) signaling, and interacts with the nucleosome remodeling and histone deacetylation (NURD) complex (Verstappen et al., 2008). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By sequencing clones obtained from a size-fractionated human brain cDNA library, Nagase et al. (1998) cloned ZEB2, which they designated KIAA0569. The deduced 1,214-amino acid protein shares significant similarity with rat Zeb1. RT-PCR analysis of human tissues detected highest ZEB2 expression in heart, brain, lung, placenta, and kidney, with moderate expression in ovary, skeletal muscle, liver, and small intestine. </p><p>Using the yeast 2-hybrid analysis of mouse embryos, Verschueren et al. (1999) identified Zeb2, which they called Smadip1. The Smadip1 protein contains a SMAD-binding domain, a homeodomain-like sequence, and 2 separate clusters of zinc fingers, one N-terminal and the other C-terminal. </p><p>Comparison of human and mouse homologs of ZEB2 at nucleotide and amino acid levels revealed 93% and 97% similarities, respectively (Wakamatsu et al., 2001). </p><p>By immunohistochemical analysis of mouse embryos, Seuntjens et al. (2009) found that Sip1 was expressed in the cortical plate, but not in neural progenitor cells. In the medial/cingulate cortex at late gestation (embryonic day 18.5), Sip1 expression was restricted to cells of the deep cortical layers. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The ZEB2 gene spans approximately 70 kb and has 10 exons (Wakamatsu et al., 2001). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By radiation hybrid analysis, Nagase et al. (1998) mapped the ZEB2 gene to chromosome 2. Wakamatsu et al. (2001) mapped the ZEB2 gene to chromosome 2q22. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Verschueren et al. (1999) found that, although SMADIP1 interacted with the MH2 domain of receptor-regulated SMADs in yeast and in vitro, its interaction with full-length SMADs (see 601595) in mammalian cells required receptor-mediated SMAD activation. Like delta-EF1, SMADIP1 bound to 5-prime-CACCT sequences in different promoters, including the Xenopus 'brachyury' (Xbra) promoter (Remacle et al., 1999). Overexpression of either full-length SMADIP1 or its C-terminal zinc finger cluster, which bound to the Xbra2 promoter in vitro, prevented expression of the endogenous Xbra gene in early Xenopus embryos. Therefore, SMADIP1 is likely to be a transcriptional repressor that may be involved in the regulation of at least 1 immediate response gene for activin-dependent signal transduction pathways. Verschueren et al. (1999) concluded that identification of this SMAD-interacting protein opens routes to investigate the mechanisms by which TGF-beta (190180) members exert their effects on expression of target genes in responsive cells and in the vertebrate embryo. </p><p>Comijn et al. (2001) reported that expression of wildtype but not mutated SIP1 downregulated mammalian E-cadherin (192090) transcription via binding to both conserved E2 boxes of the minimal E-cadherin promoter. SIP1 and Snail (SNAI1; 604238) bound to partly overlapping promoter sequences and showed similar silencing effects. SIP1 could be induced by TGFB treatment and showed high expression in several E-cadherin-negative human carcinoma cell lines. Conditional expression of SIP1 in E-cadherin-positive MDCK cells abrogated E-cadherin-mediated intercellular adhesion and simultaneously induced invasion. The authors concluded that SIP1 therefore appears to be a promoter of invasion in malignant epithelial tumors. </p><p>To explore telomerase regulation, Lin and Elledge (2003) employed a general genetic screen in HeLa cells to identify negative regulators of TERT (187270). They discovered 3 tumor suppressor/oncogene pathways involved in TERT repression, including SIP1, which mediates TGF-beta-regulated repression of TERT. </p><p>Vandewalle et al. (2005) showed that expression of mouse Sip1 in human epithelial cells caused a morphologic change from an epithelial to a mesenchymal phenotype. Dedifferentiation was accompanied by repression of several cell junction proteins and their corresponding mRNAs. In addition to E-cadherin, other genes encoding crucial proteins of tight junctions, desmosomes, and gap junctions were downregulated by Sip1. Reporter gene assays and chromatin immunoprecipitation demonstrated direct repression of promoters of some of these genes by Sip1. </p><p>TGF-beta is a key regulator of extracellular matrix collagens in mesangial cells (MCs) in diabetic nephropathy. Kato et al. (2007) found that TGF-beta increased miR192 (MIRN192; 610939) levels in primary mouse MCs, and they identified Sip1 as a target of miR192 in mouse MCs. TGF-beta treatment or transfection with miR192 decreased expression of endogenous Sip1 and activity of a reporter construct containing the 3-prime UTR of Sip1. Conversely, inhibition of miR192 enhanced reporter activity, confirming Sip1 to be an miR192 target. Glomeruli isolated from streptozotocin-injected diabetic mice and diabetic db/db mice (see 601007) showed elevated miR192 levels relative to corresponding nondiabetic controls, which paralleled increased Tgf-beta and Col1a2 (120160) expression. Transfection of mouse MCs with miR192 and short hairpin RNAs targeting delta-EF1 synergistically enhanced activity of a reporter construct containing upstream E-box elements of the Col1a2 gene. Kato et al. (2007) concluded that TGF-beta-mediated collagen regulation in MCs involves crosstalk between miR192 and the E-box repressors delta-EF1 and SIP1. </p><p>Expression of SNAI1 in epithelial cells triggers an epithelial-mesenchyme transition. Beltran et al. (2008) showed that synthesis of ZEB2 was upregulated following SNAI1 expression in human cell lines. SNAI1 did not alter ZEB2 mRNA levels, but it prevented processing of a large intron in the 5-prime UTR of ZEB2 that contains an internal ribosome entry site (IRES) necessary for ZEB2 expression. Maintenance of the 5-prime ZEB2 intron was dependent on expression of an antisense transcript that overlapped the 5-prime splice site in the intron. Ectopic overexpression of this antisense transcript in epithelial cells prevented splicing of the ZEB2 5-prime UTR, resulting in elevated ZEB2 protein expression and, consequently, downregulation of E-cadherin mRNA and protein. </p><p>Park et al. (2008) found that expression of the miR200 family of microRNAs (e.g., MIRN200A; 612090) in human cell lines was associated with an epithelial phenotype and with expression of E-cadherin, an epithelial cell marker. They identified multiple miR200 target sequences in the 3-prime UTRs of the E-cadherin transcriptional repressors ZEB1 and ZEB2. Using the 3-prime UTRs of mouse and human ZEB1 and ZEB2, they showed that endogenous miR200s suppressed ZEB1 and ZEB2 expression. Increasing miR200 levels induced mesenchymal-to-epithelial transition (MET) in human cancer cell lines, reducing their aggressiveness. Conversely, reducing miR200 levels induced epithelial-to-mesenchymal transition (EMT). Park et al. (2008) concluded that the miR200 family regulates EMT/MET by targeting ZEB1 and ZEB2, which control expression of E-cadherin. </p><p>Using mass spectrometry, Verstappen et al. (2008) found that ZEB2 associated with multiple subunits of the NURD complex, which plays a key role in transcriptional repression. Mi2-beta (CHD4; 603277) was identified as a specific cofactor for ZEB2-mediated repression of E-cadherin (CDH1; 192090). The N-terminal 289 amino acids of ZEB2 were sufficient for interaction with NURD complex subunits. In vitro studies in Xenopus oocytes showed broad Zeb2 expression at the gastrula stage, with stronger expression in neural tissues and neural crest cells at the neurula stage, suggesting a role in neural development. Endogenous Mi2-beta expression broadly overlapped Zeb2 expression, and antisense morpholino knockdown of Mi2-beta resulted in reduced Zeb2-mediated repression of Bmp4 (112262) and decreased induction of neural marker Ncam (116930). Further studies showed that a mutant ZEB2 protein (605802.0014), differing in the first 24 amino acids from the wildtype protein and causing a mild form of Mowat-Wilson syndrome (235730), was unable to interact with the NURD complex and showed decreased transcriptional repression of Bmp4. </p><p>Uterine quiescence during pregnancy is mediated by increased progesterone, which represses factors involved in contraction. Renthal et al. (2010) identified MIRN200 family members (MIRN200B, 612091; MIRN429, 612094) as microRNAs that mediate myometrial transition to a contractile phenotype. In human and mouse uterus during pregnancy, Renthal et al. (2010) found that ZEB1 and ZEB2 were transcriptional repressors of the contraction-associated genes connexin-43 (GJA1; 121014) and the oxytocin receptor (OXTR; 167055) in myometrial cells. ZEB1 was directly upregulated by progesterone at the ZEB1 promoter. During preterm labor in mice, there was an unregulation of Mirn200b/Mirn429, which downregulated Zeb1 and Zeb2, resulting in derepression of transcription of the contractility-associated proteins. In addition, Zeb1 was found to directly bind and repress Mirn200b/Mirn429, indicating a feedback mechanism. The findings implicated MIRN200B/MIRN429 and their targets, ZEB1 and ZEB2, as unique progesterone-mediated regulators of uterine quiescence and contractility during pregnancy and labor. </p><p>Using GFP-tagged endogenous Nfil3 (605327), Liu et al. (2022) showed that Nfil3 was transiently expressed to drive conventional type-1 dendritic cell (cDC1) lineage specification in mice, but that it was not required to maintain cDC1 identity. Chromatin immunoprecipitation-sequencing analysis and EMSA suggested that Nfil3 drove pre-cDC1 specification by repressing Zeb2 expression by binding to at least 1 of 3 Nfil3-binding sites in the -165 kb Zeb2 enhancer. However, mutation analysis suggested that the Nfil3 binding sites were not required for Zeb2 expression for B-cell and plasmacytoid dendritic cell (pDC) development, but that instead, in addition to Nfil3, they were likely required for binding to 1 or more factors that supported Zeb2 expression for cDC2 and monocyte development. Further analysis showed that C/EBP factors (see CEBPA, 116897) bound to the 3 Nfil3-binding sites in the -165 kb Zeb2 enhancer to support Zeb2 expression for cDC2 and monocyte development. Mice with mutation of all 3 binding sites retained pDC development, because the mutation did not ablate lymphoid progenitors, and pDCs could arise from both myeloid and lymphoid progenitors. However, mutation of all 3 binding sites ablated Zeb2 expression in myeloid progenitors and caused complete loss of pre-cDC2 specification and mature cDC2 development in mice, because Zeb2 expression was required only for pre-cDC2 specification, but not for maintenance of mature cDC2s. Mice with the triple mutation did not generate T-helper-2 (Th2) cell responses against Heligmosomoides polygyrus infection, indicating that cDC2s, but not monocytes, were required for Th2 responses. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In patients with Hirschsprung disease associated with microcephaly, mental retardation, hypertelorism, submucous cleft palate, and short stature, consistent with Mowat-Wilson syndrome (MOWS; 235730), Wakamatsu et al. (2001) identified nonsense or frameshift mutations in the SMADIP1 gene. These mutations represented null alleles, suggesting that haploinsufficiency for SMADIP1 is sufficient to cause this phenotype. Wakamatsu et al. (2001) found that the SMADIP1 gene resides in a segment on 2q22 deleted in 3 patients with the Hirschsprung disease-mental retardation syndrome. They concluded that the SMADIP1 gene appears to be essential to embryonic neural and neural crest development. </p><p>To investigate the breadth of clinical variation associated with mutations in ZFHX1B, Yamada et al. (2001) studied DNA samples from 6 patients with clinical features similar to those described for ZFHX1B deficiency, except that they did not have Hirschsprung disease. The results showed the R695X mutation (605802.0002) to be present in 3 cases, with 3 novel mutations being identified in the other 3 patients. All mutations occurred in 1 allele and were de novo events. The results demonstrated that ZFHX1B deficiency is an autosomal dominant complex developmental disorder and that individuals with functional null mutations present with mental retardation, delayed motor development, epilepsy, and a wide spectrum of clinically heterogeneous features suggestive of neurocristopathies at the cephalic, cardiac, and vagal levels. </p><p>Amiel et al. (2001) found that 8 of 19 patients with Hirschsprung disease and mental retardation had large-scale ZFHX1B deletions or truncating mutations. These results allowed further delineation of the spectrum of malformations ascribed to haploinsufficiency of this gene, which includes frequent features such as hypospadias and agenesis of the corpus callosum. Thus, the ZFHX1B gene, which encodes a transcriptional corepressor of Smad target genes, may play a role not only in the patterning of neural crest-derived cells and of the central nervous system but also in the development of midline structures in humans. </p><p>Zweier et al. (2002) analyzed the ZFHX1B gene in 5 patients, 3 of whom had Hirschsprung disease syndrome, 2 with and 1 without the facial phenotype described by Mowat et al. (1998), and 2 of whom had the distinct facial gestalt without Hirschsprung disease. Zweier et al. (2002) excluded large deletions in all 5 patients and found truncating ZFHX1B mutations (605802.0007-605802.0010) in all 4 patients with the characteristic facial phenotype but not in the patient with syndromic Hirschsprung disease without the distinct facial appearance. Zweier et al. (2002) suggested the name Mowat-Wilson syndrome (235730) for the clinical entity of distinct facial appearance, mental retardation, and variable multiple congenital anomalies (MCA). </p><p>Ishihara et al. (2004) identified 5 novel nonsense and frameshift mutations in the ZFHX1B gene in patients with Mowat-Wilson syndrome and characterized the clinical features and molecular basis of a total of 27 cases with mutations or deletions in ZFHX1B. All of the deletions were of paternal origin, and clinical features in cases with deletions of up to about 5 Mb overlapped those found in cases with nonsense and frameshift mutations. However, 2 of their patients with large deletions (10.42 Mb and 8.83 Mb) had significantly delayed psychomotor development, and 1 of them also had a cleft palate and complicated heart disease, features not previously reported in patients with Mowat-Wilson syndrome. </p><p>Zweier et al. (2006) reported a 5-year-old boy with a facial gestalt similar to that seen in Mowat-Wilson syndrome but who exhibited an unusually mild phenotype and in whom they identified heterozygosity for a splice site mutation in the ZFHX1B gene (605802.0014). </p><p>Heinritz et al. (2006) described a 2.5-year-old boy with a heterozygous missense mutation in the ZFHX1B gene (605802.0015) who had bilateral cleft lip and palate and brachytelephalangy, features unusual in Mowat-Wilson syndrome. </p><p>Dastot-Le Moal et al. (2007) stated that more than 110 different mutations in the ZEB2 gene had been described. Nonsense mutations accounted for approximately 41% of the known punctual mutations and were localized mainly in exon 8. No obvious genotype-phenotype correlations had been observed. </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>The majority of ZEB2 mutations identified in patients with Mowat-Wilson syndrome lead to haploinsufficiency through premature termination or large gene deletions. In 3 unrelated patients with a mild form of MOWS, Ghoumid et al. (2013) identified 3 different missense mutations in the ZEB2 gene (see, e.g., S1071P, 605802.0016 and H1045R, 605802.0017). All 3 mutations occurred in the conserved C-terminal zinc finger cluster domain. In vitro functional expression studies showed that these 3 missense mutations lost the ability to bind to the E-cadherin (CDH1; 192090) promoter and to repress transcription of this target gene, consistent with a loss of function and without a dominant-negative effect. However, these mutant mRNAs showed significant phenotypic rescue of morpholino knockout zebrafish embryos: complete rescue with S1071P (84%) and partial rescue with H1045R (55%), indicating that they are hypomorphic alleles; wildtype mRNA showed 81% rescue. The patients had mild facial gestalt of MOWS and moderate intellectual disability, but no microcephaly, heart defects, or HSCR. The variable embryonic rescue correlated with the severity of the patients' phenotype. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>To clarify the molecular mechanisms underlying the clinical features of Hirschsprung disease-mental retardation syndrome, Van de Putte et al. (2003) generated mice that carried a Zfhx1b mutation comparable to those found in several human patients. They showed that Zfhx1b knockout mice did not develop postotic vagal neural crest cells, the precursors of the enteric nervous system that is affected in patients with Hirschsprung disease, and displayed a delamination arrest of cranial neural crest cells, which form the skeletomuscular elements of the vertebral head. This suggests that the gene product is essential for the development of vagal neural crest precursors and the migratory behavior of cranial neural crest in the mouse. Furthermore, they showed that the gene product is involved in the specification of neuroepithelium. Sip1-knockout embryos died around embryonic day 9.5, with failed neural tube closure, lack of a sharp boundary between the neural plate and the rest of the ectoderm, and lack of the first branchial arch. </p><p>Van de Putte et al. (2007) found that conditional deletion of Zeb2 in mouse neural crest precursors was embryonic lethal. Mutant mice displayed craniofacial and gastrointestinal malformations similar to those of patients with Mowat-Wilson syndrome. In addition, mutant mice had defects in the heart, melanoblasts, and sympathetic and parasympathetic anlagen. </p><p>A single layer of neuroepithelial cells lining the embryonic neural tube gives rise to the entire repertoire of neurons, astrocytes, and oligodendrocytes in the adult central nervous system. Seuntjens et al. (2009) found that conditional Sip1 deletion in young mouse neurons induced premature production of upper layer neurons at the expense of deep layers, precocious and increased generation of glial precursors, and elevated numbers of astrocytes at early postnatal stages. Microarray analysis showed that Ntf3 (162660) and Fgf9 (600921) were over- and prematurely expressed in mutant brains. In the absence of Sip1, there was also a premature peak of MAPK (see 176948) signaling in neural progenitor cells. Seuntjens et al. (2009) concluded that SIP1 functions in the postmitotic compartment of the neocortex to control the expression of growth factor genes that feed back to progenitors to regulate production of the neurons and glial cells required for corticogenesis. </p><p>Ghoumid et al. (2013) found that morpholino knockout of the zebrafish Zeb2 ortholog sip1b in zebrafish embryos resulted in severe neurodevelopmental abnormalities, including small brains and defects of tectum development, as well as impaired neuronal crest cell migration with a lack of development of pharyngeal arches and jaw cartilages. </p><p>Using insertional mutagenesis, El-Kasti et al. (2012) developed a line of transgenic rats that exhibited autosomal dominant postnatal lethality in males only. Female transgenic rats exhibited delayed development, but thrived and had normal life spans. Death in male transgenic rats was due to delayed renal development, leading to severe renal insufficiency. Southern blot and sequencing suggested that a head-to-tail concatamer of 2 copies of the transgene caused a 12-kb genomic deletion 1.2 Mb upstream of the Zeb2 gene. This region is syntenic to a 3.5-Mb region upstream of the human ZEB2 gene on chromosome 2q22.3. The Zeb2 coding region and transcript size were unaffected by the deletion, but Zeb2 expression in kidney was significantly reduced. Immunohistochemical analysis revealed reduced Zeb2 protein expression in neonatal transgenic rat kidney, but normal Zeb2 expression in brain. Microarray analysis revealed downregulation of androgen-related genes in both male and female transgenic mice, and male transgenic kidneys showed aberrant expression of genes involved in renal development and function. Using an in vitro transcription assay, El-Kasti et al. (2012) found that the deleted region in transgenic rats functioned as an enhancer for Zeb2 in both sequence orientations. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>17 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, ARG549TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852980,
|
|
|
|
|
|
gnomAD: rs137852980,
|
|
|
|
|
|
ClinVar: RCV000005020
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Hirschsprung disease associated with microcephaly, mental retardation, hypertelorism, submucous cleft palate, and short stature (235730), Wakamatsu et al. (2001) identified an A-to-T transversion at nucleotide 1645 of the SMADIP1 gene, resulting in an arg-to-ter substitution at codon 549 (R549X). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, ARG695TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852981,
|
|
|
|
|
|
|
|
ClinVar: RCV000005021, RCV000213082
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Hirschsprung disease associated with microcephaly, mental retardation, hypertelorism, submucous cleft palate, and short stature (235730), Wakamatsu et al. (2001) identified a C-to-T transition at nucleotide 2083 of the SMADIP1 gene, resulting in an arg-to-ter substitution at codon 695 (R695X). </p><p>In a study of 6 patients with clinical features similar to those reported in patients with ZFHX1B mutations but without Hirschsprung disease, Yamada et al. (2001) found that 3 had the R695X mutation. Thus, Hirschsprung disease is not a consistent feature. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, 4-BP DEL, NT1173
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776603,
|
|
|
|
|
|
|
|
ClinVar: RCV000005022
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Hirschsprung disease associated with microcephaly and mental retardation, hypertelorism, submucous cleft palate, and short stature (235730), Wakamatsu et al. (2001) identified a 4-bp deletion (AACA) at nucleotide 1173 of the SMADIP1 gene, resulting in a frameshift at codon 392 leading to a termination codon at amino acid residue 394 in exon 8. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, 1-BP INS, 1421A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776604,
|
|
|
|
|
|
|
|
ClinVar: RCV000005023, RCV000498048, RCV002390091
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Hirschsprung disease associated with microcephaly and mental retardation, hypertelorism, submucous cleft palate, and short stature (235730) originally reported by Mowat et al. (1998), Cacheux et al. (2001) identified insertion of an adenine residue following nucleotide 1421 of the SMADIP1 gene, resulting in a frameshift and leading to a termination codon at amino acid residue 481 in exon 8. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, 2-BP INS, 760CA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776605,
|
|
|
|
|
|
|
|
ClinVar: RCV000005024
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 25-year-old male patient with many features of the Hirschsprung disease-mental retardation syndrome but without Hirschsprung disease (235730), Yamada et al. (2001) found a 2-bp insertion (760insCA) in the ZFHX1B gene. The patient showed hypertelorism and microcephaly (head circumference 2 standard deviations below the mean) at birth. He developed epilepsy at age 1 year. He showed delayed motor development, with neck control developing at age 8 months and walking without support at age 2 years. He was severely mentally retarded, with only a few words of speech. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, 1-BP INS, 2453T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776606,
|
|
|
|
|
|
|
|
ClinVar: RCV000005025
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Hirschsprung disease-mental retardation syndrome (235730), Amiel et al. (2001) found a 1-bp insertion (2453insT) in the ZFHX1B gene. The patient had the characteristic facies, with sunken eyes, downslanting palpebral fissures, strabismus, thick eyebrows with lateral flaring, saddle nose, pointed chin, thick antehelix, and rotated ears with uplifted, fleshy earlobes. The patient did not have agenesis of the corpus callosum but did have hydronephrosis as well as heart defects: atrial septal defects, ventricular septal defects, and pulmonic stenosis. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, 1-BP DEL, 1892A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776607,
|
|
|
|
|
|
|
|
ClinVar: RCV000005026
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Hirschsprung disease-mental retardation syndrome (235730), Zweier et al. (2002) found a heterozygous 1-bp deletion (1892delA) in exon 8 of the ZFHX1B gene, resulting in a premature stop codon after 14 amino acids. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, 2-BP INS, 553TG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776608,
|
|
|
|
|
|
gnomAD: rs587776608,
|
|
|
|
|
|
ClinVar: RCV000005027
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with many features of the Hirschsprung disease-mental retardation syndrome (235730) but without Hirschsprung disease, Zweier et al. (2002) found a heterozygous 2-bp insertion in exon 5 in the ZFHX1B gene, leading to a stop codon after 27 amino acids. To investigate if this truncating mutation led to mRNA decay, Zweier et al. (2002) performed RT-PCR of mRNA from the patient's peripheral blood and found the mutated transcript. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, SER852TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852982,
|
|
|
|
|
|
gnomAD: rs137852982,
|
|
|
|
|
|
ClinVar: RCV000005028
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with many features of the Hirschsprung disease-mental retardation syndrome (235730) but without Hirschsprung disease, Zweier et al. (2002) found a heterozygous C-to-G substitution in exon 8 of the ZFHX1B gene, resulting in a ser852-to-ter substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, 2-BP INS, 3567CC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776609,
|
|
|
|
|
|
|
|
ClinVar: RCV000005029
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Hirschsprung disease-mental retardation syndrome (235730), Zweier et al. (2002) found a heterozygous 2-bp insertion (3567insCC) in exon 10, resulting in a frameshift and an enlarged protein of 1,241 amino acids. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 HIRSCHSPRUNG DISEASE-MENTAL RETARDATION SYNDROME, LATE INFANTILE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, 3-BP DEL, 295AAC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776610,
|
|
|
|
|
|
gnomAD: rs587776610,
|
|
|
|
|
|
ClinVar: RCV000005030, RCV000490485
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Yoneda et al. (2002) reported a 48-year-old woman with late infantile-onset mental retardation who developed megacolon. Although the patient had no typical clinical features of Hirschsprung disease-mental retardation syndrome (235730), a 3-bp deletion eliminating asn99 was identified in exon 3 of the ZFHX1B gene. The woman was born of nonconsanguineous parents. She was noted to have mental retardation but received a full education in elementary school. She sometimes had constipation but did not require medication until age 48 years, when she presented with severe constipation and was found to have megacolon. This patient would appear to represent an intermediate stage between the full-blown Hirschsprung disease-mental retardation syndrome and Hirschsprung disease-mental retardation syndrome without Hirschsprung disease. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, 300-KB DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000005031
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with typical features of Mowat-Wilson syndrome (235730), Zweier et al. (2003) described a deletion of approximately 300 kb on chromosome 2q22, encompassing the ZFHX1B gene, as defined by FISH and marker analysis. The patient was pictured at age 10 years with a facial gestalt typical of Mowat-Wilson syndrome. Birth weight and length were at the 90th centile. He had ventricular septal defect and pulmonary stenosis. He was described as being affectionate and happy. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, 1-BP DEL, 1862T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776611,
|
|
|
|
|
|
|
|
ClinVar: RCV000005032
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a sister and brother with Mowat-Wilson syndrome (235730), McGaughran et al. (2005) identified heterozygosity for a 1-bp deletion (1862delT) in exon 8 of the ZFHX1B gene, resulting in a stop codon at position 645 and predicting a truncated protein missing the homeodomain and the C-terminal zinc finger domain. The mutation was not found in the unaffected parents' lymphocyte-derived DNA, suggesting germline mosaicism in the sibs. McGaughran et al. (2005) stated that this was the first report of a sib recurrence of Mowat-Wilson syndrome. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, IVS1AS, G-A, -1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776612,
|
|
|
|
|
|
|
|
ClinVar: RCV000005033
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 5-year-old boy with a facial gestalt of Mowat-Wilson syndrome (235730) and an unusually mild phenotype, Zweier et al. (2006) identified heterozygosity for a G-to-A transition at the -1 position in the splice acceptor site of exon 2 of the ZFHX1B gene (alternatively, -70G-A), predicted to result in skipping of exon 2 including the start codon. The aberrant transcript contains an alternative upstream start codon, resulting in a mutant protein differing only for the first 24 amino acids from the wildtype protein. The mutation was excluded in both parents, revealing its de novo origin. The patient's facial gestalt was less striking than the majority of MWS patients, and his psychomotor development was much better than expected in classic MWS. Except for increased disposition for seizures on EEG and body measurements at the 3rd centile, he showed no other anomalies frequently observed in MWS. </p><p>Verstappen et al. (2008) showed the protein resulting from the -70G-A mutation was unable to interact with the NURD complex, which plays a key role in transcriptional repression, as well as decreased transcriptional repression of Bmp4 (112262). The findings were important because they demonstrated the effect of aberrant function of a single domain of the ZEB2 protein, which resulted in a relatively milder phenotype compared to complete haploinsufficiency. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, GLN1119ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852983,
|
|
|
|
|
|
|
|
ClinVar: RCV000005034
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2.5-year-old boy with the overall facial phenotype of Mowat-Wilson syndrome (235730) but with cleft lip and palate and lacking the characteristic eyebrows, Heinritz et al. (2006) identified heterozygosity for a de novo 3356A-G transition in exon 10 of the ZFHX1B gene, resulting in a gln1119-to-arg (Q1119R) substitution. The patient also had brachytelephalangy, which the authors stated had never been described before in Mowat-Wilson syndrome. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, SER1071PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397515448,
|
|
|
|
|
|
|
|
ClinVar: RCV000050218, RCV002513706
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with a relatively mild form of Mowat-Wilson syndrome (235730), Ghoumid et al. (2013) identified a heterozygous c.3211T-C transition in the ZEB2 gene, resulting in a ser1071-to-pro (S1071P) substitution at a highly conserved residue in the C-terminal zinc finger domain. The mutation was not present in the mother, in 200 control chromosomes, or in SNP databases; DNA from the father was not available. In vitro functional expression studies showed that the mutant protein lost the ability to bind to the E-cadherin (CDH1; 192090) promoter and to repress transcription of this target gene, consistent with a loss of function and without a dominant-negative effect. However, this mutant mRNA showed complete phenotypic rescue of morpholino knockout zebrafish embryos, indicating that it is a hypomorphic allele. The patient had the typical facial gestalt of the disorder, moderate intellectual disability, delayed walking, and seizures, but no microcephaly and no cardiac or gastrointestinal abnormalities. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 MOWAT-WILSON SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
ZEB2, HIS1045ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397515449,
|
|
|
|
|
|
|
|
ClinVar: RCV000050219
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with a relatively mild form of Mowat-Wilson syndrome (235730), Ghoumid et al. (2013) identified a heterozygous de novo c.3134A-G transition in the ZEB2 gene, resulting in a his1045-to-arg (H1045R) substitution at a highly conserved residue in the C-terminal zinc finger domain. The mutation was not present in 200 control chromosomes or in SNP databases. In vitro functional expression studies showed that the mutant protein lost the ability to bind to the E-cadherin (CDH1; 192090) promoter and to repress transcription of this target gene, consistent with a loss of function and without a dominant-negative effect. However, this mutant mRNA showed 53% phenotypic rescue of morpholino knockout zebrafish embryos, indicating that it is a hypomorphic allele. The patient had a mild facial gestalt of the disorder, moderate intellectual disability, delayed walking, hippocampal abnormalities, frontal cortical atrophy, and hypospadias, but no microcephaly and no cardiac or gastrointestinal abnormalities. </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">
|
|
Postigo and Dean (2000)
|
|
</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">
|
|
Amiel, J., Espinosa-Parrilla, Y., Steffann, J., Gosset, P., Pelet, A., Prieur, M., Boute, O., Choiset, A., Lacombe, D., Philip, N., Le Merrer, M., Tanaka, H., Till, M., Touraine, R., Toutain, A., Vekemans, M., Munnich, A., Lyonnet, S.
|
|
<strong>Large-scale deletions and SMADIP1 truncating mutations in syndromic Hirschsprung disease with involvement of midline structures.</strong>
|
|
Am. J. Hum. Genet. 69: 1370-1377, 2001.
|
|
|
|
|
|
[PubMed: 11595972]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/324342]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Beltran, M., Puig, I., Pena, C., Garcia, J. M., Alvarez, A. B., Pena, R., Bonilla, F., Garcia de Herreros, A.
|
|
<strong>A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition.</strong>
|
|
Genes Dev. 22: 756-769, 2008.
|
|
|
|
|
|
[PubMed: 18347095]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gad.455708]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cacheux, V., Dastot-Le Moal, F., Kaariainen, H., Bondurand, N., Rintala, R., Boissier, B., Wilson, M., Mowat, D., Goossens, M.
|
|
<strong>Loss-of-function mutations in SIP1 Smad interacting protein 1 result in a syndromic Hirschsprung disease.</strong>
|
|
Hum. Molec. Genet. 10: 1503-1510, 2001.
|
|
|
|
|
|
[PubMed: 11448942]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.14.1503]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Comijn, J., Berx, G., Vermassen, P., Verschueren, K., van Grunsven, L., Bruyneel, E., Mareel, M., Huylebroeck, D., van Roy, F.
|
|
<strong>The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion.</strong>
|
|
Molec. Cell 7: 1267-1278, 2001.
|
|
|
|
|
|
[PubMed: 11430829]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s1097-2765(01)00260-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dastot-Le Moal, F., Wilson, M., Mowat, D., Collot, N., Niel, F., Goossens, M.
|
|
<strong>ZFHX1B mutations in patients with Mowat-Wilson syndrome.</strong>
|
|
Hum. Mutat. 28: 313-321, 2007.
|
|
|
|
|
|
[PubMed: 17203459]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20452]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
El-Kasti, M. M., Wells, T., Carter, D. A.
|
|
<strong>A novel long-range enhancer regulates postnatal expression of Zeb2: implications for Mowat-Wilson syndrome phenotypes.</strong>
|
|
Hum. Molec. Genet. 21: 5429-5442, 2012.
|
|
|
|
|
|
[PubMed: 23001561]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/dds389]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ghoumid, J., Drevillon, L., Alavi-Naini, S. M., Bondurand, N., Rio, M., Briand-Suleau, A., Nasser, M., Goodwin, L., Raymond, P., Yanicostas, C., Goossens, M., Lyonnet, S., Mowat, D., Amiel, J., Soussi-Yanicostas, N., Giurgea, I.
|
|
<strong>ZEB2 zinc-finger missense mutations lead to hypomorphic alleles and a mild Mowat-Wilson syndrome.</strong>
|
|
Hum. Molec. Genet. 22: 2652-2661, 2013.
|
|
|
|
|
|
[PubMed: 23466526]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddt114]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Heinritz, W., Zweier, C., Froster, U. G., Strenge, S., Kujat, A., Syrbe, S., Rauch, A., Schuster, V.
|
|
<strong>A missense mutation in the ZFHX1B gene associated with an atypical Mowat-Wilson syndrome phenotype.</strong>
|
|
Am. J. Med. Genet. 140A: 1223-1227, 2006.
|
|
|
|
|
|
[PubMed: 16688751]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31267]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ishihara, N., Yamada, K., Yamada, Y., Miura, K., Kato, J., Kuwabara, N., Hara, Y., Kobayashi, Y., Hoshino, K., Nomura, Y., Mimaki, M., Ohya, K., and 16 others.
|
|
<strong>Clinical and molecular analysis of Mowat-Wilson syndrome associated with ZFHX1B mutations and deletions at 2q22-q24.1. (Letter)</strong>
|
|
J. Med. Genet. 41: 387-393, 2004.
|
|
|
|
|
|
[PubMed: 15121779]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2003.016154]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kato, M., Zhang, J., Wang, M., Lanting, L., Yuan, H., Rossi, J. J., Natarajan, R.
|
|
<strong>MicroRNA-192 in diabetic kidney glomeruli and its function in TGF-beta-induced collagen expression via inhibition of E-box repressors.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 3432-3437, 2007.
|
|
|
|
|
|
[PubMed: 17360662]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0611192104]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lin, S.-Y., Elledge, S. J.
|
|
<strong>Multiple tumor suppressor pathways negatively regulate telomerase.</strong>
|
|
Cell 113: 881-889, 2003.
|
|
|
|
|
|
[PubMed: 12837246]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(03)00430-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Liu, T.-T., Kim, S., Desai, P., Kim, D.-H., Huang, X., Ferris, S. T., Wu, R., Ou, F., Egawa, T., Van Dyken, S. J., Diamond, M. S., Johnson, P. F., Kubo, M., Murphy, T. L., Murphy, K. M.
|
|
<strong>Ablation of cDC2 development by triple mutations within the Zeb2 enhancer.</strong>
|
|
Nature 607: 142-148, 2022.
|
|
|
|
|
|
[PubMed: 35732734]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41586-022-04866-z]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McGaughran, J., Sinnott, S., Dastot-Le Moal, F., Wilson, M., Mowat, D., Sutton, B., Goossens, M.
|
|
<strong>Recurrence of Mowat-Wilson syndrome in siblings with the same proven mutation.</strong>
|
|
Am. J. Med. Genet. 137A: 302-304, 2005.
|
|
|
|
|
|
[PubMed: 16088920]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.30896]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mowat, D. R., Croaker, G. D. H., Cass, D. T., Kerr, B. A., Chaitow, J., Ades, L. C., Chia, N. L., Wilson, M. J.
|
|
<strong>Hirschsprung disease, microcephaly, mental retardation, and characteristic facial features: delineation of a new syndrome and identification of a locus at chromosome 2q22-q23.</strong>
|
|
J. Med. Genet. 35: 617-623, 1998.
|
|
|
|
|
|
[PubMed: 9719364]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.35.8.617]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nagase, T., Ishikawa, K., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O.
|
|
<strong>Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.</strong>
|
|
DNA Res. 5: 31-39, 1998.
|
|
|
|
|
|
[PubMed: 9628581]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/dnares/5.1.31]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Park, S.-M., Gaur, A. B., Lengyel, E., Peter, M. E.
|
|
<strong>The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2.</strong>
|
|
Genes Dev. 22: 894-907, 2008. Note: Erratum: Genes Dev. 23: 1378 only, 2009.
|
|
|
|
|
|
[PubMed: 18381893]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gad.1640608]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Postigo, A. A., Dean, D. C.
|
|
<strong>Differential expression and function of members of the zfh-1 family of zinc finger/homeodomain repressors.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 6391-6396, 2000.
|
|
|
|
|
|
[PubMed: 10841546]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.97.12.6391]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Remacle, J. E., Kraft, H., Lerchner, W., Wuytens, G., Collart, C., Verschueren, K., Smith, J. C., Huylebroeck, D.
|
|
<strong>New mode of DNA binding of multi-zinc finger transcription factors: deltaEF1 family members bind with two hands to two target sites.</strong>
|
|
EMBO J. 18: 5073-5084, 1999.
|
|
|
|
|
|
[PubMed: 10487759]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/emboj/18.18.5073]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Renthal, N. E., Chen, C.-C., Williams. K. C., Gerard, R. D., Prange-Kiel, J., Mendelson, C. R.
|
|
<strong>miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor.</strong>
|
|
Proc. Nat. Acad. Sci. 107: 20828-20833, 2010.
|
|
|
|
|
|
[PubMed: 21079000]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.1008301107]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Seuntjens, E., Nityanandam, A., Miquelajauregui, A., Debruyn, J., Stryjewska, A., Goebbels, S., Nave, K.-A., Huylebroeck, D., Tarabykin, V.
|
|
<strong>Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors.</strong>
|
|
Nature Neurosci. 12: 1373-1380, 2009.
|
|
|
|
|
|
[PubMed: 19838179]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nn.2409]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van de Putte, T., Francis, A., Nelles, L., van Grunsven, L. A., Huylebroeck, D.
|
|
<strong>Neural crest-specific removal of Zfhx1b in mouse leads to a wide range of neurocristopathies reminiscent of Mowat-Wilson syndrome.</strong>
|
|
Hum. Molec. Genet. 16: 1423-1436, 2007.
|
|
|
|
|
|
[PubMed: 17478475]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddm093]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van de Putte, T., Maruhashi, M., Francis, A., Nelles, L., Kondoh, H., Huylebroeck, D., Higashi, Y.
|
|
<strong>Mice lacking Zfhx1b, the gene that codes for Smad-interacting protein-1, reveal a role for multiple neural crest cell defects in the etiology of Hirschsprung disease-mental retardation syndrome.</strong>
|
|
Am. J. Hum. Genet. 72: 465-470, 2003.
|
|
|
|
|
|
[PubMed: 12522767]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/346092]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vandewalle, C., Comijn, J., De Craene, B., Vermassen, P., Bruyneel, E., Andersen, H., Tulchinsky, E., Van Roy, F., Berx, G.
|
|
<strong>SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions.</strong>
|
|
Nucleic Acids Res. 33: 6566-6578, 2005.
|
|
|
|
|
|
[PubMed: 16314317]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/nar/gki965]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Verschueren, K., Remacle, J. E., Collart, C., Kraft, H., Baker, B. S., Tylzanowski, P., Nelles, L., Wuytens, G., Su, M.-T., Bodmer, R., Smith, J. C., Huylebroeck, D.
|
|
<strong>SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5-prime-CACCT sequences in candidate target genes.</strong>
|
|
J. Biol. Chem. 274: 20489-20498, 1999.
|
|
|
|
|
|
[PubMed: 10400677]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.274.29.20489]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Verstappen, G., van Grunsven, L. A., Michiels, C., Van de Putte, T., Souopgui, J., Van Damme, J., Bellefroid, E., Vandekerckhove, J., Huylebroeck, D.
|
|
<strong>Atypical Mowat-Wilson patient confirms the importance of the novel association between ZFHX1B/SIP1 and NuRD corepressor complex.</strong>
|
|
Hum. Molec. Genet. 17: 1175-1183, 2008.
|
|
|
|
|
|
[PubMed: 18182442]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddn007]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wakamatsu, N., Yamada, Y., Yamada, K., Ono, T., Nomura, N., Taniguchi, H., Kitoh, H., Mutoh, N., Yamanaka, T., Mushiake, K., Kato, K., Sonta, S., Nagaya, M.
|
|
<strong>Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease.</strong>
|
|
Nature Genet. 27: 369-370, 2001.
|
|
|
|
|
|
[PubMed: 11279515]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/86860]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yamada, K., Yamada, Y., Nomura, N., Miura, K., Wakako, R., Hayakawa, C., Matsumoto, A., Kumagai, T., Yoshimura, I., Miyazaki, S., Kato, K., Sonta, S., Ono, H., Yamanaka, T., Nagaya, M., Wakamatsu, N.
|
|
<strong>Nonsense and frameshift mutations in ZFHX1B, encoding Smad-interacting protein 1, cause a complex developmental disorder with a great variety of clinical features.</strong>
|
|
Am. J. Hum. Genet. 69: 1178-1185, 2001.
|
|
|
|
|
|
[PubMed: 11592033]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/324343]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yoneda, M., Fujita, T., Yamada, Y., Yamada, K., Fujii, A., Inagaki, T., Nakagawa, H., Shimada, A., Kishikawa, M., Nagaya, M., Azuma, T., Kuriyama, M., Wakamatsu, N.
|
|
<strong>Late infantile Hirschsprung disease-mental retardation syndrome with a 3-bp deletion in ZFHX1B.</strong>
|
|
Neurology 59: 1637-1640, 2002.
|
|
|
|
|
|
[PubMed: 12451214]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/01.wnl.0000034842.78350.4e]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zweier, C., Albrecht, B., Mitulla, B., Behrens, R., Beese, M., Gillessen-Kaesbach, G., Rott, H.-D., Rauch, A.
|
|
<strong>'Mowat-Wilson' syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.</strong>
|
|
Am. J. Med. Genet. 108: 177-181, 2002.
|
|
|
|
|
|
[PubMed: 11891681]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zweier, C., Horn, D., Kraus, C., Rauch, A.
|
|
<strong>Atypical ZFHX1B mutation associated with a mild Mowat-Wilson syndrome phenotype.</strong>
|
|
Am. J. Med. Genet. 140A: 869-872, 2006.
|
|
|
|
|
|
[PubMed: 16532472]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31196]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zweier, C., Temple, I. K., Beemer, F., Zackai, E., Lerman-Sagie, T., Weschke, B., Anderson, C. E., Rauch, A.
|
|
<strong>Characterisation of deletions of the ZFHX1B region and genotype-phenotype analysis in Mowat-Wilson syndrome.</strong>
|
|
J. Med. Genet. 40: 601-605, 2003.
|
|
|
|
|
|
[PubMed: 12920073]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.40.8.601]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Bao Lige - updated : 01/05/2024<br>Patricia A. Hartz - updated : 12/13/2013<br>Cassandra L. Kniffin - updated : 7/24/2013<br>Cassandra L. Kniffin - updated : 3/21/2011<br>Patricia A. Hartz - updated : 3/18/2010<br>Patricia A. Hartz - updated : 12/8/2009<br>Cassandra L. Kniffin - updated : 10/29/2009<br>Patricia A. Hartz - updated : 5/30/2008<br>Patricia A. Hartz - updated : 4/29/2008<br>Cassandra L. Kniffin - updated : 5/29/2007<br>Patricia A. Hartz - updated : 4/18/2007<br>Marla J. F. O'Neill - updated : 10/11/2006<br>Marla J. F. O'Neill - updated : 8/11/2006<br>Marla J. F. O'Neill - updated : 10/3/2005<br>Stylianos E. Antonarakis - updated : 11/24/2004<br>Marla J. F. O'Neill - updated : 6/11/2004<br>Victor A. McKusick - updated : 10/1/2003<br>Victor A. McKusick - updated : 2/27/2003<br>Victor A. McKusick - updated : 1/22/2003<br>Deborah L. Stone - updated : 4/25/2002<br>George E. Tiller - updated : 12/12/2001
|
|
</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">
|
|
Ada Hamosh : 3/29/2001
|
|
</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 : 02/17/2025<br>mgross : 01/05/2024<br>alopez : 07/02/2018<br>mgross : 12/17/2013<br>mcolton : 12/13/2013<br>carol : 9/13/2013<br>carol : 7/24/2013<br>ckniffin : 7/24/2013<br>mgross : 5/22/2013<br>alopez : 11/26/2012<br>terry : 4/26/2011<br>wwang : 3/25/2011<br>ckniffin : 3/21/2011<br>mgross : 3/22/2010<br>terry : 3/18/2010<br>mgross : 1/25/2010<br>terry : 12/8/2009<br>wwang : 12/2/2009<br>ckniffin : 10/29/2009<br>wwang : 11/24/2008<br>joanna : 8/27/2008<br>mgross : 5/30/2008<br>mgross : 4/29/2008<br>wwang : 6/11/2007<br>ckniffin : 5/29/2007<br>mgross : 4/18/2007<br>mgross : 4/18/2007<br>mgross : 4/18/2007<br>wwang : 10/13/2006<br>terry : 10/11/2006<br>wwang : 8/29/2006<br>wwang : 8/17/2006<br>terry : 8/11/2006<br>wwang : 10/10/2005<br>terry : 10/3/2005<br>mgross : 3/9/2005<br>mgross : 11/24/2004<br>tkritzer : 6/25/2004<br>carol : 6/14/2004<br>terry : 6/11/2004<br>terry : 3/18/2004<br>tkritzer : 10/21/2003<br>tkritzer : 10/6/2003<br>tkritzer : 10/1/2003<br>tkritzer : 5/19/2003<br>tkritzer : 2/28/2003<br>terry : 2/27/2003<br>cwells : 1/29/2003<br>tkritzer : 1/22/2003<br>carol : 4/25/2002<br>terry : 4/25/2002<br>alopez : 1/11/2002<br>cwells : 1/10/2002<br>terry : 12/20/2001<br>cwells : 12/18/2001<br>cwells : 12/14/2001<br>cwells : 12/14/2001<br>cwells : 12/12/2001<br>mgross : 10/31/2001<br>alopez : 4/13/2001<br>alopez : 4/2/2001<br>alopez : 3/29/2001
|
|
</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>
|
|
|
|
|