5587 lines
536 KiB
Text
5587 lines
536 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
|
|
|
|
- *120470 - DCC NETRIN 1 RECEPTOR; DCC
|
|
|
|
|
|
- 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=120470"><span class="mim-navbar-menu-font"> Contact Us </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li>
|
|
|
|
<a href="/mimmatch/">
|
|
|
|
<span class="mim-navbar-menu-font">
|
|
<span class="mim-tip-bottom" qtip_title="<strong>MIMmatch</strong>" qtip_text="MIMmatch is a way to follow OMIM entries that interest you and to find other researchers who may share interest in the same entries. <br /><br />A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.">
|
|
MIMmatch
|
|
</span>
|
|
</span>
|
|
</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDonateDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Donate <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="donateDropdown">
|
|
<li>
|
|
<a href="https://secure.jhu.edu/form/OMIM" target="_blank" onclick="gtag('event', 'mim_donation', {'destination': 'secure.jhu.edu'})"> Donate! </a>
|
|
</li>
|
|
<li>
|
|
<a href="/donors"> Donors </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimHelpDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Help <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="helpDropdown">
|
|
<li>
|
|
<a href="/help/faq"> Frequently Asked Questions (FAQs) </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/search"> Search Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/linking"> Linking Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/api"> API Help </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/external"> External Links </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/agreement"> Use Agreement </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/copyright"> Copyright </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="#" id="mimShowTips" class="mim-tip-hint" title="Click to reveal all tips on the page. You can also hover over individual elements to reveal the tip."><span class="mim-navbar-menu-font"><span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span></span></a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimSearch" class="hidden-print">
|
|
|
|
<div class="container">
|
|
|
|
<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
|
|
|
|
<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
|
|
<input type="hidden" id="mimSearchStart" name="start" value="1" />
|
|
<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
|
|
<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
|
|
<div class="form-group">
|
|
<div class="input-group">
|
|
<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
|
|
<div class="input-group-btn">
|
|
<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
|
|
<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
|
|
<ul class="dropdown-menu dropdown-menu-right">
|
|
<li class="dropdown-header">
|
|
Advanced Search
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/entry"> OMIM </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/geneMap"> Gene Map </a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/history"> Search History </a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
</div>
|
|
</div>
|
|
<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
|
|
<span class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</form>
|
|
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
<!-- <div id="mimSearch"> -->
|
|
|
|
|
|
|
|
|
|
<div id="mimContent">
|
|
|
|
|
|
|
|
<div class="container hidden-print">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
|
|
<div id="mimAlertBanner">
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
|
|
|
|
<div id="mimFloatingTocMenu" class="small" role="navigation">
|
|
|
|
<p>
|
|
<span class="h4">*120470</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="#biochemicalFeatures">Biochemical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#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="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#history">History</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/120470">Table View</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000187323;t=ENST00000442544" 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=1630" 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=120470" 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=ENSG00000187323;t=ENST00000442544" 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_005215,XM_011525844,XM_017025568,XM_017025569,XM_047437311" 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_005215" 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=120470" 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=00391&isoform_id=00391_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/DCC" 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/181493,181498,181506,441146,441147,453210,553248,553249,553250,553251,1326437,13366256,71297068,110431348,119583395,119583396,119583397,119583398,194380234,296434474,767998294,1034603483,1034603485,2217316196,2462559655,2462559657,2462559659,2462559661" 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/P43146" 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=1630" 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=ENSG00000187323;t=ENST00000442544" 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=DCC" 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=DCC" 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+1630" 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/DCC" 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:1630" 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/1630" 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=chr18&hgg_gene=ENST00000442544.7&hgg_start=52340197&hgg_end=53535899&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:2701" 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/dcc" 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=120470[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=120470[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/DCC/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/ENSG00000187323" 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=DCC" 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=DCC" 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=DCC" 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=DCC&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/PA27170" 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:2701" 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/FBgn0011592.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:94869" 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/DCC#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:94869" 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/1630/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=1630" 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=WBGene00006776;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-011101-2" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="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:1630" 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=DCC&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">
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
120470
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
DCC NETRIN 1 RECEPTOR; DCC
|
|
|
|
</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">
|
|
NETRIN RECEPTOR DCC<br />
|
|
DELETED IN COLORECTAL CARCINOMA<br />
|
|
COLORECTAL CANCER-RELATED CHROMOSOME SEQUENCE 18; CRC18<br />
|
|
CRCR1
|
|
</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=DCC" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">DCC</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/18/191?start=-3&limit=10&highlight=191">18q21.2</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr18:52340197-53535899&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'})">18:52,340,197-53,535,899</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=114500,133239,617542,157600" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="4">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/18/191?start=-3&limit=10&highlight=191">
|
|
18q21.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Colorectal cancer, somatic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/114500"> 114500 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Esophageal carcinoma, somatic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/133239"> 133239 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Gaze palsy, familial horizontal, with progressive scoliosis, 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/617542"> 617542 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Mirror movements 1 and/or agenesis of the corpus callosum
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/157600"> 157600 </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/120470" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/120470" 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 DCC gene encodes a functional receptor for netrin (NTN1; <a href="/entry/601614">601614</a>) and mediates axon outgrowth and the steering response (summary by <a href="#21" class="mim-tip-reference" title="Li, W., Lee, J., Vikis, H. G., Lee, S.-H., Liu, G., Aurandt, J., Shen, T.-L., Fearon, E. R., Guan, J.-L., Han, M., Rao, Y., Hong, K., Guan, K.-L. <strong>Activation of FAK and Src are receptor-proximal events required for netrin signaling.</strong> Nature Neurosci. 7: 1213-1221, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15494734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15494734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15494734[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/nn1329" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15494734">Li et al., 2004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15494734" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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><a href="#44" class="mim-tip-reference" title="Vogelstein, B., Fearon, E. R., Hamilton, S. R., Kern, S. E., Preisinger, A. C., Leppert, M., Nakamura, Y., White, R., Smits, A. M. M., Bos, J. L. <strong>Genetic alterations during colorectal-tumor development.</strong> New Eng. J. Med. 319: 525-532, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2841597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2841597</a>] [<a href="https://doi.org/10.1056/NEJM198809013190901" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2841597">Vogelstein et al. (1988)</a> found that chromosome 18 sequences were lost frequently in colorectal carcinomas (73%) and in advanced adenomas (47%), but only occasionally in earlier-stage adenomas (11 to 13%). Taken in connection with other findings of changes in chromosome 17, as well as chromosome 5, these findings suggested a model wherein the steps required for malignancy often involve the activation of a dominantly acting oncogene coupled with the loss of several genes that normally suppress tumorigenesis. The critical area in chromosome 18 appeared to reside between 18q21.3 and the telomere. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2841597" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Fearon, E. R., Cho, K. R., Nigro, J. M., Kern, S. E., Simons, J. W., Ruppert, J. M., Hamilton, S. R., Preisinger, A. C., Thomas, G., Kinzler, K. W., Vogelstein, B. <strong>Identification of a chromosome 18q gene that is altered in colorectal cancers.</strong> Science 247: 49-56, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2294591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2294591</a>] [<a href="https://doi.org/10.1126/science.2294591" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2294591">Fearon et al. (1990)</a> cloned a contiguous stretch of DNA, comprising 370 kb, from the region of 18q suspected to contain the tumor suppressor gene. Potential exons in the 370-kb region were defined by human-rodent sequence identities, and the expression of potential exons was assessed by an 'exon-connection' strategy based on the polymerase chain reaction. Expressed exons were used as probes for screening of cDNA to obtain clones that encoded a gene the authors termed DCC ('deleted in colorectal carcinomas'). This cDNA was encoded by at least 8 exons. The predicted amino acid sequence specified a protein with sequence similarity to neural cell adhesion molecules (<a href="/entry/116930">116930</a>) and related cell surface glycoproteins. While the DCC gene was expressed in most normal tissues, including colonic mucosa, its expression was greatly reduced or absent in most colorectal carcinomas tested. Somatic mutations within the DCC gene observed in colorectal cancers included a homozygous deletion of the 5-prime end, a point mutation within one of the introns, and 10 examples of DNA insertions within a 0.17-kb fragment immediately downstream of 1 of the exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2294591" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In the embryonic mouse brain, <a href="#14" class="mim-tip-reference" title="Jamuar, S. S., Schmitz-Abe, K., D'Gama, A. M., Drottar, M., Chan, W.-M., Peeva, M., Servattalab, S., Lam, A.-T. N., Delgado, M. R., Clegg, N. J., Al Zayed, Z., Dogar, M. A., and 14 others. <strong>Biallelic mutations in human DCC cause developmental split-brain syndrome.</strong> Nature Genet. 49: 606-612, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28250456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28250456</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28250456[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/ng.3804" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28250456">Jamuar et al. (2017)</a> found expression of the Dcc gene in the telencephalic cortical plate as well as in the developing brainstem nuclei. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28250456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneStructure" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneStructureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneStructureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#4" class="mim-tip-reference" title="Cho, K. R., Oliner, J. D., Simons, J. W., Hedrick, L., Fearon, E. R., Preisinger, A. C., Hedge, P., Silverman, G. A., Vogelstein, B. <strong>The DCC gene: structural analysis and mutations in colorectal carcinomas.</strong> Genomics 19: 525-531, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8188295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8188295</a>] [<a href="https://doi.org/10.1006/geno.1994.1102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8188295">Cho et al. (1994)</a> commented that the DCC gene encodes a protein with sequence similarity to cell adhesion molecules such as N-CAM (<a href="/entry/116930">116930</a>). Studying a YAC contig containing the entire DCC coding region, they showed that the DCC gene spans approximately 1.4 Mb. They used lambda phage clones to demonstrate the existence of 29 DCC exons, and the sequences of the exon-intron boundaries were determined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8188295" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="biochemicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimBiochemicalFeaturesFold" id="mimBiochemicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimBiochemicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimBiochemicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
<a href="#47" class="mim-tip-reference" title="Xu, K., Wu, Z., Renier, N., Antipenko, A., Tzvetkova-Robev, D., Xu, Y., Minchenko, M., Nardi-Dei, V., Rajashankar, K. R., Himanen, J., Tessier-Lavigne, M., Nikolov, D. B. <strong>Structures of netrin-1 bound to two receptors provide insight into its axon guidance mechanism.</strong> Science 344: 1275-1279, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24876346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24876346</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24876346[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/10.1126/science.1255149" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24876346">Xu et al. (2014)</a> determined the structures of a functional NTN1 (<a href="/entry/601614">601614</a>) region, alone and in complexes with NEO1 (<a href="/entry/601907">601907</a>) and DCC. NTN1 has a rigid elongated structure containing 2 receptor-binding sites at opposite ends through which it brings together receptor molecules. The ligand/receptor complexes reveal 2 distinct architectures: a 2:2 heterotetramer and a continuous ligand/receptor assembly. The differences result from different lengths of the linker connecting receptor domains fibronectin type III domain 4 (FN4) and FN5, which differs among DCC and NEO1 splice variants, providing a basis for diverse signaling outcomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24876346" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Using molecular markers in an interspecific backcross between C57BL/6J and Mus spretus, <a href="#16" class="mim-tip-reference" title="Justice, M. J., Gilbert, D. J., Kinzler, K. W., Vogelstein, B., Buchberg, A. M., Ceci, J. D., Matsuda, Y., Chapman, V. M., Patriotis, C., Makris, A., Tsichlis, P. N., Jenkins, N. A., Copeland, N. G. <strong>A molecular genetic linkage map of mouse chromosome 18 reveals extensive linkage conservation with human chromosomes 5 and 18.</strong> Genomics 13: 1281-1288, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1354644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1354644</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90047-v" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1354644">Justice et al. (1992)</a> mapped the corresponding gene to mouse chromosome 18. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1354644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#45" class="mim-tip-reference" title="Vogelstein, B. <strong>Personal Communication.</strong> Baltimore, Md. 11/30/1995."None>Vogelstein (1995)</a> stated that the precise location of the DCC gene was thought to be 18q21.3.</p><p><a href="#42" class="mim-tip-reference" title="Thiagalingam, S., Lengauer, C., Leach, F. S., Schutte, M., Hahn, S. A., Overhauser, J., Willson, J. K. V., Markowitz, S., Hamilton, S. R., Kern, S. E., Kinzler, K. W., Vogelstein, B. <strong>Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers.</strong> Nature Genet. 13: 343-346, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673134</a>] [<a href="https://doi.org/10.1038/ng0796-343" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8673134">Thiagalingam et al. (1996)</a> evaluated sporadic colon cancer tumors for allelic deletions. They defined a minimally lost region (MLR) on chromosome 18q21 which extended between markers D18S535 and D18S858. It encompassed 16 cM between D18S535 and 20CO3 and included 2 candidate tumor suppressor genes: DPC4 (<a href="/entry/600993">600993</a>) and DCC. DPC4 was deleted in up to one-third of cases and DCC or a neighboring gene was deleted in the remaining tumors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8673134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#17" class="mim-tip-reference" title="Keino-Masu, K., Masu, M., Hinck, L., Leonardo, E. D., Chan, S. S.-Y., Culotti, J. G., Tessier-Lavigne, M. <strong>Deleted in colorectal cancer (DCC) encodes a netrin receptor.</strong> Cell 87: 175-185, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8861902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8861902</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81336-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8861902">Keino-Masu et al. (1996)</a> noted that the establishment of neuronal connections involves the accurate guidance of developing axons to their targets through the combined actions of attractive and repulsive guidance cues in the extracellular environment. Diffusible chemoattractants secreted by target cells are involved, as well as diffusible chemorepellents secreted by nontarget cells which generate exclusion zones that axons avoid (<a href="#18" class="mim-tip-reference" title="Keynes, R., Cook, G. M. W. <strong>Axon guidance molecules.</strong> Cell 83: 161-169, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585933/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585933</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90157-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7585933">Keynes and Cook, 1995</a>). Two families of guidance molecules, the netrins (see netrin-1, <a href="/entry/601614">601614</a>) and semaphorins (see <a href="/entry/601281">601281</a> and <a href="/entry/601124">601124</a>), are proteins that can function as diffusible attractants or repellents for developing neurons, but the receptors and signal transduction mechanisms through which they produce their effects are poorly understood. Netrins are chemoattractants for commissural axons in the vertebral spinal cord. <a href="#17" class="mim-tip-reference" title="Keino-Masu, K., Masu, M., Hinck, L., Leonardo, E. D., Chan, S. S.-Y., Culotti, J. G., Tessier-Lavigne, M. <strong>Deleted in colorectal cancer (DCC) encodes a netrin receptor.</strong> Cell 87: 175-185, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8861902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8861902</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81336-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8861902">Keino-Masu et al. (1996)</a> showed that DCC, a transmembrane protein of the immunoglobulin superfamily, is expressed on spinal commissural axons and possesses netrin-1-binding activity. Moreover, an antibody to DCC selectively blocked the netrin-1-dependent outgrowth of commissural axons in vitro. These results indicated that DCC is a receptor or a component of a receptor that mediates the effects of netrin-1 on commissural axons, and they complement genetic evidence for interactions between DCC and netrin homologs in C. elegans (UNC40; see <a href="#3" class="mim-tip-reference" title="Chan, S. S.-Y., Zheng, H., Su, M.-W., Wilk, R., Killeen, M. T., Hedgecock, E. M., Culotti, J. G. <strong>UNC-40, a C. elegans homolog of the DCC (deleted in colorectal cancer), is required in motile cells responding to UNC-6 netrin cues.</strong> Cell 87: 187-195, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8861903/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8861903</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81337-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8861903">Chan et al., 1996</a>) and Drosophila (frazzled; see <a href="#19" class="mim-tip-reference" title="Kolodziej, P. A., Timpe, L. C., Mitchell, K. J., Fried, S. R., Goodman, C. S., Jan, L. Y., Jan, Y. N. <strong>Frazzled encodes a Drosophila member of the DCC immunoglobulin subfamily and is required for CNS and motor axon guidance.</strong> Cell 87: 197-204, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8861904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8861904</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81338-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8861904">Kolodziej et al., 1996</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8861904+8861902+7585933+8861903" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 RT-PCR, <a href="#12" class="mim-tip-reference" title="Gotley, D. C., Reeder, J. A., Fawcett, J., Walsh, M. D., Bates, P., Simmons, D. L., Antalis, T. M. <strong>The deleted in colon cancer (DCC) gene is consistently expressed in colorectal cancers and metastases.</strong> Oncogene 13: 787-795, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8761300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8761300</a>]" pmid="8761300">Gotley et al. (1996)</a> detected DCC mRNA in all colonic tissue specimens through all stages of tumor development. Using monoclonal antibodies against DCC, they found DCC protein is abundant in normal human bladder and is detectable in colon, pancreas and kidney, but not in liver. DCC protein could be detected in varying abundance in all specimens of normal colonic mucosa analyzed as well as in all specimens of adenomatous polyps, colorectal carcinoma and colorectal liver metastases. In some patients, tumor tissue contained less DCC protein than the adjacent normal mucosa. <a href="#12" class="mim-tip-reference" title="Gotley, D. C., Reeder, J. A., Fawcett, J., Walsh, M. D., Bates, P., Simmons, D. L., Antalis, T. M. <strong>The deleted in colon cancer (DCC) gene is consistently expressed in colorectal cancers and metastases.</strong> Oncogene 13: 787-795, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8761300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8761300</a>]" pmid="8761300">Gotley et al. (1996)</a> found no cases of complete loss of DCC mRNA or protein in colon cancers or metastases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8761300" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#27" class="mim-tip-reference" title="Mehlen, P., Rabizadeh, S., Snipas, S. J., Assa-Munt, N., Salvesen, G. S., Bredesen, D. E. <strong>The DCC gene produce induces apoptosis by a mechanism requiring receptor proteolysis.</strong> Nature 395: 801-804, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9796814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9796814</a>] [<a href="https://doi.org/10.1038/27441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9796814">Mehlen et al. (1998)</a> showed that DCC induces apoptosis in the absence of ligand binding, but blocks apoptosis when engaged by netrin-1. Furthermore, DCC is a caspase substrate, and mutation of the site at which caspase-3 (CASP3; <a href="/entry/600636">600636</a>) cleaves DCC suppresses the proapoptotic effect of DCC completely. These results indicated the DCC may function as a tumor-suppressor protein by inducing apoptosis in settings in which ligand is unavailable (for example, during metastasis or tumor growth beyond local blood supply) through functional caspase cascades by a mechanism that requires cleavage of DCC at asp1290. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9796814" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The axonal chemoattractant netrin-1 guides spinal commissural axons by activating its receptor DCC. <a href="#11" class="mim-tip-reference" title="Galko, M. J., Tessier-Lavigne, M. <strong>Function of an axonal chemoattractant modulated by metalloprotease activity.</strong> Science 289: 1365-1367, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10958786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10958786</a>] [<a href="https://doi.org/10.1126/science.289.5483.1365" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10958786">Galko and Tessier-Lavigne (2000)</a> found that chemical inhibitors of metalloproteases potentiate netrin-mediated axon outgrowth in vitro. <a href="#11" class="mim-tip-reference" title="Galko, M. J., Tessier-Lavigne, M. <strong>Function of an axonal chemoattractant modulated by metalloprotease activity.</strong> Science 289: 1365-1367, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10958786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10958786</a>] [<a href="https://doi.org/10.1126/science.289.5483.1365" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10958786">Galko and Tessier-Lavigne (2000)</a> also found that DCC is a substrate for metalloprotease-dependent ectodomain shedding, and that the inhibitors block proteolytic processing of DCC and cause an increase in DCC protein levels on axons within spinal cord explants. Thus, <a href="#11" class="mim-tip-reference" title="Galko, M. J., Tessier-Lavigne, M. <strong>Function of an axonal chemoattractant modulated by metalloprotease activity.</strong> Science 289: 1365-1367, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10958786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10958786</a>] [<a href="https://doi.org/10.1126/science.289.5483.1365" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10958786">Galko and Tessier-Lavigne (2000)</a> suggested that potentiation of netrin activity by inhibitors may result from stabilization of DCC on the axons, and proteolytic activity may regulate axon migration by controlling the number of functional extracellular axon guidance receptors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10958786" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#39" class="mim-tip-reference" title="Stein, E., Zou, Y., Poo, M., Tessier-Lavigne, M. <strong>Binding of DCC by netrin-1 to mediate axon guidance independent of adenosine A2B receptor activation.</strong> Science 291: 1976-1982, 2001. Note: Expression of Concern: Science 378: 1284 only, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11239160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11239160</a>] [<a href="https://doi.org/10.1126/science.1059391" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11239160">Stein et al. (2001)</a> demonstrated that netrin-1 binds DCC and that the DCC cytoplasmic domain fused to a heterologous receptor ectodomain can mediate guidance through a mechanism involving derepression of cytoplasmic domain multimerization. Activation of the adenosine A2B receptor (<a href="/entry/600446">600446</a>), proposed to contribute to netrin effects on axons, is not required for rat commissural axon outgrowth or Xenopus spinal axon attraction to netrin-1. Thus, <a href="#39" class="mim-tip-reference" title="Stein, E., Zou, Y., Poo, M., Tessier-Lavigne, M. <strong>Binding of DCC by netrin-1 to mediate axon guidance independent of adenosine A2B receptor activation.</strong> Science 291: 1976-1982, 2001. Note: Expression of Concern: Science 378: 1284 only, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11239160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11239160</a>] [<a href="https://doi.org/10.1126/science.1059391" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11239160">Stein et al. (2001)</a> concluded that DCC plays a central role in netrin signaling of axon growth and guidance independent of A2B receptor activation. Note that an expression of concern has been published for the article by <a href="#39" class="mim-tip-reference" title="Stein, E., Zou, Y., Poo, M., Tessier-Lavigne, M. <strong>Binding of DCC by netrin-1 to mediate axon guidance independent of adenosine A2B receptor activation.</strong> Science 291: 1976-1982, 2001. Note: Expression of Concern: Science 378: 1284 only, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11239160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11239160</a>] [<a href="https://doi.org/10.1126/science.1059391" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11239160">Stein et al. (2001)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11239160" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Axonal growth cones that cross the nervous system midline change their responsiveness to midline guidance cues: they become repelled by the repellent Slit (<a href="/entry/603746">603746</a>) and simultaneously lose responsiveness to the attractant netrin. These mutually reinforcing changes help to expel growth cones from the midline by making a once-attractive environment appear repulsive. <a href="#38" class="mim-tip-reference" title="Stein, E., Tessier-Lavigne, M. <strong>Hierarchical organization of guidance receptors: silencing of netrin attraction by Slit through a Robo/DCC receptor complex.</strong> Science 291: 1928-1938, 2001. Note: Expression of Concern: Science 378: 1284 only, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11239147/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11239147</a>] [<a href="https://doi.org/10.1126/science.1058445" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11239147">Stein and Tessier-Lavigne (2001)</a> provided evidence that these 2 changes are causally linked: in the growth cones of embryonic Xenopus spinal axons, activation of the Slit receptor Roundabout (Robo; <a href="/entry/602430">602430</a>) silences the attractive effect of netrin-1, but not its growth-stimulatory effect, through direct binding of the cytoplasmic domain of Robo to that of the netrin receptor DCC. Biologically, this hierarchical silencing mechanism helps to prevent a tug-of-war between attractive and repulsive signals in the growth cone that might cause confusion. Molecularly, silencing is enabled by a modular and interlocking design of the cytoplasmic domains of these potentially antagonistic receptors that predetermines the outcome of their simultaneous activation. Note that an expression of concern was published for the article by <a href="#38" class="mim-tip-reference" title="Stein, E., Tessier-Lavigne, M. <strong>Hierarchical organization of guidance receptors: silencing of netrin attraction by Slit through a Robo/DCC receptor complex.</strong> Science 291: 1928-1938, 2001. Note: Expression of Concern: Science 378: 1284 only, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11239147/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11239147</a>] [<a href="https://doi.org/10.1126/science.1058445" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11239147">Stein and Tessier-Lavigne (2001)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11239147" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Forcet, C., Stein, E., Pays, L., Corset, V., Llambi, F., Tessier-Lavigne, M., Mehlen, P. <strong>Netrin-1-mediated axon outgrowth requires deleted in colorectal cancer-dependent MAPK activation.</strong> Nature 417: 443-447, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11986622/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11986622</a>] [<a href="https://doi.org/10.1038/nature748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11986622">Forcet et al. (2002)</a> showed that in embryonic kidney cells expressing full-length, but not cytoplasmic domain-truncated, DCC, NTN1 causes increased transient phosphorylation and activity of ERK1 (<a href="/entry/601795">601795</a>) and ERK2 (<a href="/entry/176948">176948</a>), but not of JNK1 (<a href="/entry/601158">601158</a>), JNK2 (<a href="/entry/602896">602896</a>), or p38 (MAPK14; <a href="/entry/600289">600289</a>). This phosphorylation was mediated by MEK1 (MAP2K1; <a href="/entry/176872">176872</a>) and/or MEK2 (MAP2K2; <a href="/entry/601263">601263</a>). NTN1 also activated the transcription factor ELK1 (<a href="/entry/311040">311040</a>) and serum response element-regulated gene expression. Immunoprecipitation analysis showed interaction of full-length DCC with MEK1/2 in the presence or absence of NTN1. <a href="#10" class="mim-tip-reference" title="Forcet, C., Stein, E., Pays, L., Corset, V., Llambi, F., Tessier-Lavigne, M., Mehlen, P. <strong>Netrin-1-mediated axon outgrowth requires deleted in colorectal cancer-dependent MAPK activation.</strong> Nature 417: 443-447, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11986622/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11986622</a>] [<a href="https://doi.org/10.1038/nature748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11986622">Forcet et al. (2002)</a> showed that activation of Dcc by Ntn1 in rat embryonic day-13 dorsal spinal cord stimulates and is required for the outgrowth of commissural axons and Erk1/2 activation. Immunohistochemical analysis demonstrated expression of activated Erk1/2 in embryonic commissural axons, and this expression was diminished in Dcc or Ntn1 knockout animals. <a href="#10" class="mim-tip-reference" title="Forcet, C., Stein, E., Pays, L., Corset, V., Llambi, F., Tessier-Lavigne, M., Mehlen, P. <strong>Netrin-1-mediated axon outgrowth requires deleted in colorectal cancer-dependent MAPK activation.</strong> Nature 417: 443-447, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11986622/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11986622</a>] [<a href="https://doi.org/10.1038/nature748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11986622">Forcet et al. (2002)</a> concluded that the MAPK pathway is involved in responses to NTN1 and proposed that ERK activation affects axonal growth by phosphorylation of microtubule-associated proteins and neurofilaments. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11986622" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#31" class="mim-tip-reference" title="Nishiyama, M., Hoshino, A., Tsai, L., Henley, J. R., Goshima, Y., Tessier-Lavigne, M., Poo, M., Hong, K. <strong>Cyclic AMP/GMP-dependent modulation of Ca(2+) channels sets the polarity of nerve growth-cone turning.</strong> Nature 423: 990-995, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12827203/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12827203</a>] [<a href="https://doi.org/10.1038/nature01751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12827203">Nishiyama et al. (2003)</a> reported that the ratio of cyclic AMP to cyclic GMP activities sets the polarity of netrin-1-induced axon guidance: high ratios favor attraction, whereas low ratios favor repulsion. Whole-cell recordings of calcium currents in Xenopus spinal neuron growth cones indicated that cyclic nucleotide signaling directly modulates the activity of L-type calcium channels in axonal growth cones. Furthermore, cyclic GMP signaling activated by an arachidonate 12-lipoxygenase metabolite suppressed L-type calcium channel activity triggered by netrin-1 and was required for growth cone repulsion mediated by the DCC-UNC5 (see <a href="/entry/603610">603610</a>) receptor complex. By linking cyclic AMP and cyclic GMP signaling and modulation of calcium channel activity in growth cones, these findings delineated an early membrane-associated event responsible for signal transduction during bidirectional axon guidance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12827203" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#27" class="mim-tip-reference" title="Mehlen, P., Rabizadeh, S., Snipas, S. J., Assa-Munt, N., Salvesen, G. S., Bredesen, D. E. <strong>The DCC gene produce induces apoptosis by a mechanism requiring receptor proteolysis.</strong> Nature 395: 801-804, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9796814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9796814</a>] [<a href="https://doi.org/10.1038/27441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9796814">Mehlen et al. (1998)</a> showed that DCC induces apoptosis conditionally: by functioning as a dependence receptor, DCC induces apoptosis unless it is engaged by its ligand netrin-1. <a href="#26" class="mim-tip-reference" title="Mazelin, L., Bernet, A., Bonod-Bidaud, C., Pays, L., Arnaud, S., Gespach, C., Bredesen, D. E., Scoazec, J.-Y., Mehlen, P. <strong>Netrin-1 controls colorectal tumorigenesis by regulating apoptosis.</strong> Nature 431: 80-84, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15343335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15343335</a>] [<a href="https://doi.org/10.1038/nature02788" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15343335">Mazelin et al. (2004)</a> demonstrated that inhibition of cell death by enforced expression of netrin-1 in mouse gastrointestinal tract led to the spontaneous formation of hyperplastic and neoplastic lesions. Moreover, in the adenomatous polyposis coli mutant background associated with adenoma formation, enforced expression of netrin-1 engendered aggressive adenocarcinomatous malignancies. <a href="#26" class="mim-tip-reference" title="Mazelin, L., Bernet, A., Bonod-Bidaud, C., Pays, L., Arnaud, S., Gespach, C., Bredesen, D. E., Scoazec, J.-Y., Mehlen, P. <strong>Netrin-1 controls colorectal tumorigenesis by regulating apoptosis.</strong> Nature 431: 80-84, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15343335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15343335</a>] [<a href="https://doi.org/10.1038/nature02788" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15343335">Mazelin et al. (2004)</a> concluded that netrin-1 can promote intestinal tumor development, probably by regulating cell survival. Thus, a netrin-1 receptor or receptors function as conditional tumor suppressors. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9796814+15343335" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Netrin proteins play a role in the developing nervous system by promoting both axonal outgrowth and axonal guidance in pathfinding. <a href="#22" class="mim-tip-reference" title="Liu, G., Beggs, H., Jurgensen, C., Park, H.-T., Tang, H., Gorski, J., Jones, K. R., Reichardt, L. F., Wu, J., Rao, Y. <strong>Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth and attraction.</strong> Nature Neurosci. 7: 1222-1232, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15494732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15494732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15494732[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/nn1331" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15494732">Liu et al. (2004)</a>, <a href="#21" class="mim-tip-reference" title="Li, W., Lee, J., Vikis, H. G., Lee, S.-H., Liu, G., Aurandt, J., Shen, T.-L., Fearon, E. R., Guan, J.-L., Han, M., Rao, Y., Hong, K., Guan, K.-L. <strong>Activation of FAK and Src are receptor-proximal events required for netrin signaling.</strong> Nature Neurosci. 7: 1213-1221, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15494734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15494734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15494734[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/nn1329" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15494734">Li et al. (2004)</a>, and <a href="#32" class="mim-tip-reference" title="Ren, X., Ming, G., Xie, Y., Hong, Y., Sun, D., Zhao, Z., Feng, Z., Wang, Q., Shim, S., Chen, Z., Song, H., Mei, L., Xiong, W. <strong>Focal adhesion kinase in netrin-1 signaling.</strong> Nature Neurosci. 7: 1204-1212, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15494733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15494733</a>] [<a href="https://doi.org/10.1038/nn1330" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15494733">Ren et al. (2004)</a> simultaneously reported a complex network of intracellular signaling downstream from netrin-1 (<a href="/entry/601614">601614</a>) involving DCC, focal adhesion kinase (FAK; <a href="/entry/600758">600758</a>), and FYN (<a href="/entry/137025">137025</a>), a member of the SRC family kinases (see <a href="/entry/190090">190090</a>). In neurons cultured from rat cerebral cortex, <a href="#22" class="mim-tip-reference" title="Liu, G., Beggs, H., Jurgensen, C., Park, H.-T., Tang, H., Gorski, J., Jones, K. R., Reichardt, L. F., Wu, J., Rao, Y. <strong>Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth and attraction.</strong> Nature Neurosci. 7: 1222-1232, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15494732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15494732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15494732[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/nn1331" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15494732">Liu et al. (2004)</a> found that netrin-1 induced tyrosine phosphorylation of FAK and FYN, and coimmunoprecipitation studies showed direct interaction of FAK and FYN with DCC. Inhibition of FYN inhibited FAK phosphorylation, and FYN mutants inhibited the attractive turning responses to netrin. Neurons lacking the FAK gene showed reduced axonal outgrowth and attractive turning responses to netrin. In cultured neurons from chick and mouse, <a href="#21" class="mim-tip-reference" title="Li, W., Lee, J., Vikis, H. G., Lee, S.-H., Liu, G., Aurandt, J., Shen, T.-L., Fearon, E. R., Guan, J.-L., Han, M., Rao, Y., Hong, K., Guan, K.-L. <strong>Activation of FAK and Src are receptor-proximal events required for netrin signaling.</strong> Nature Neurosci. 7: 1213-1221, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15494734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15494734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15494734[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/nn1329" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15494734">Li et al. (2004)</a> found that netrin increased tyrosine phosphorylation of DCC and FAK. Coimmunoprecipitation studies showed that DCC interacted directly with FAK and SRC to form a complex and that FAK and SRC cooperated to stimulate DCC phosphorylation by SRC. <a href="#21" class="mim-tip-reference" title="Li, W., Lee, J., Vikis, H. G., Lee, S.-H., Liu, G., Aurandt, J., Shen, T.-L., Fearon, E. R., Guan, J.-L., Han, M., Rao, Y., Hong, K., Guan, K.-L. <strong>Activation of FAK and Src are receptor-proximal events required for netrin signaling.</strong> Nature Neurosci. 7: 1213-1221, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15494734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15494734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15494734[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/nn1329" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15494734">Li et al. (2004)</a> suggested that phosphorylated DCC acts as a kinase-coupled receptor and that FAK and SRC act downstream of DCC in netrin signaling. <a href="#32" class="mim-tip-reference" title="Ren, X., Ming, G., Xie, Y., Hong, Y., Sun, D., Zhao, Z., Feng, Z., Wang, Q., Shim, S., Chen, Z., Song, H., Mei, L., Xiong, W. <strong>Focal adhesion kinase in netrin-1 signaling.</strong> Nature Neurosci. 7: 1204-1212, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15494733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15494733</a>] [<a href="https://doi.org/10.1038/nn1330" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15494733">Ren et al. (2004)</a> found that inhibition of FAK phosphorylation inhibited netrin-1-induced axonal outgrowth and guidance. The authors suggested that FAK may also function as a scaffolding protein and play a role in cytoskeletal reorganization that is necessary for neurite outgrowth and turning. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15494732+15494734+15494733" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Colon-Ramos, D. A., Margeta, M. A., Shen, K. <strong>Glia promote local synaptogenesis through UNC-6 (netrin) signaling in C. elegans.</strong> Science 318: 103-106, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17916735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17916735</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17916735[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/10.1126/science.1143762" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17916735">Colon-Ramos et al. (2007)</a> showed that connectivity between 2 interneurons in C. elegans, AIY and RIA, is orchestrated by a pair of glial cells that express UNC6 (netrin-1). In the postsynaptic neuron RIA, the netrin receptor UNC40 (DCC) plays a conventional guidance role directing outgrowth of the RIA process ventrally toward the glia. The authors determined that in the presynaptic neuron AIY, UNC40 plays an unexpected and theretofore uncharacterized role: it cell-autonomously promotes assembly of presynaptic terminals in the immediate vicinity of the glial cell endfeet. <a href="#5" class="mim-tip-reference" title="Colon-Ramos, D. A., Margeta, M. A., Shen, K. <strong>Glia promote local synaptogenesis through UNC-6 (netrin) signaling in C. elegans.</strong> Science 318: 103-106, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17916735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17916735</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17916735[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/10.1126/science.1143762" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17916735">Colon-Ramos et al. (2007)</a> concluded that netrin can be used both for guidance and local synaptogenesis and suggested that glial cells can function as guideposts during the assembly of neural circuits in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17916735" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#41" class="mim-tip-reference" title="Tcherkezian, J., Brittis, P. A., Thomas, F., Roux, P. P., Flanagan, J. G. <strong>Transmembrane receptor DCC associates with protein synthesis machinery and regulates translation.</strong> Cell 141: 632-644, 2010. Note: Erratum: Cell 184: 2520 only, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20434207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20434207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20434207[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2010.04.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20434207">Tcherkezian et al. (2010)</a> found that Ddc partly colocalized with the translational machinery in embryonic mouse spinal commissural axon growth cones and in rat hippocampal neuron dendrites. Ddc coprecipitated with components of translation machinery in transfected 293 cells, and this coprecipitation required the Ddc intracellular domain. Ddc associated particularly with translation initiation components. Mutation analysis and mass spectrometry revealed that the P1 motif of the Ddc intracellular domain interacted specifically and directly with ribosomal protein L5 (RPL5; <a href="/entry/603634">603634</a>). Labeling studies revealed that Ddc overlapped with newly synthesized proteins at the tips of commissural neuron filopodia and in hippocampal neurons. Netrin-1 promoted translation in a Ddc-dependent manner and reduced association of Ddc with translation components. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20434207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Congenital Mirror Movements 1 and/or Agenesis of the Corpus Callosum</em></strong></p><p>
|
|
<a href="#37" class="mim-tip-reference" title="Srour, M., Riviere, J.-B., Pham, J. M. T., Dube, M.-P., Girard, S., Morin, S., Dion, P. A., Asselin, G., Rochefort, D., Hince, P., Diab, S., Sharafaddinzadeh, N., Chouinard, S., Theoret, H., Charron, F., Rouleau, G. A. <strong>Mutations in DCC cause congenital mirror movements.</strong> Science 328: 592 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20431009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20431009</a>] [<a href="https://doi.org/10.1126/science.1186463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20431009">Srour et al. (2010)</a> identified 2 frameshift mutations in the DCC gene in 2 families with congenital mirror movements (MRMV1; <a href="/entry/157600">157600</a>). In a large French Canadian family, they identified a splice site mutation in intron 6 leading to a frameshift and exon skipping (<a href="#0003">120470.0003</a>), and in an Iranian family they identified a single-nucleotide insertion in exon 3 (<a href="#0004">120470.0004</a>). <a href="#37" class="mim-tip-reference" title="Srour, M., Riviere, J.-B., Pham, J. M. T., Dube, M.-P., Girard, S., Morin, S., Dion, P. A., Asselin, G., Rochefort, D., Hince, P., Diab, S., Sharafaddinzadeh, N., Chouinard, S., Theoret, H., Charron, F., Rouleau, G. A. <strong>Mutations in DCC cause congenital mirror movements.</strong> Science 328: 592 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20431009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20431009</a>] [<a href="https://doi.org/10.1126/science.1186463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20431009">Srour et al. (2010)</a> proposed that DCC mutations in individuals with congenital mirror movements cause a reduction in gene dosage and less robust midline guidance, which may lead to a partial failure of axonal fiber crossing and development of abnormal ipsilateral connection. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20431009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 individuals from 4 unrelated multigenerational families with congenital mirror movements and/or agenesis of the corpus callosum, <a href="#25" class="mim-tip-reference" title="Marsh, A. P. L., Heron, D., Edwards, T. J., Quartier, A., Galea, C., Nava, C., Rastetter, A., Moutard, M.-L., Anderson, V., Bitoun, P., Bunt, J., Faudet, A., and 41 others. <strong>Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance.</strong> Nature Genet. 49: 511-514, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28250454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28250454</a>] [<a href="https://doi.org/10.1038/ng.3794" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28250454">Marsh et al. (2017)</a> identified heterozygous mutations in the DCC gene (<a href="#0006">120470.0006</a>-<a href="#0009">120470.0009</a>). The mutations were found by a combination of methods, including linkage analysis, whole-exome sequencing, and direct sequencing. Two mutations were truncating mutations, predicted to result in haploinsufficiency, and 2 were missense mutations affecting the netrin-1 binding domain. Heterozygous missense DCC mutations were subsequently found in 5 of 70 probands with isolated ACC. Functional studies of the variants and studies of patient cells were not performed. In a review of individuals with mutations in the DCC gene in their study and in the literature, <a href="#25" class="mim-tip-reference" title="Marsh, A. P. L., Heron, D., Edwards, T. J., Quartier, A., Galea, C., Nava, C., Rastetter, A., Moutard, M.-L., Anderson, V., Bitoun, P., Bunt, J., Faudet, A., and 41 others. <strong>Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance.</strong> Nature Genet. 49: 511-514, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28250454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28250454</a>] [<a href="https://doi.org/10.1038/ng.3794" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28250454">Marsh et al. (2017)</a> found significant incomplete penetrance: the penetrance of mirror movements was estimated to be 42%, and the penetrance of ACC was estimated to be 26%. There was some evidence for a male bias in phenotypic manifestations, and in vitro studies suggested that androgens could influence DCC expression. <a href="#25" class="mim-tip-reference" title="Marsh, A. P. L., Heron, D., Edwards, T. J., Quartier, A., Galea, C., Nava, C., Rastetter, A., Moutard, M.-L., Anderson, V., Bitoun, P., Bunt, J., Faudet, A., and 41 others. <strong>Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance.</strong> Nature Genet. 49: 511-514, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28250454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28250454</a>] [<a href="https://doi.org/10.1038/ng.3794" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28250454">Marsh et al. (2017)</a> concluded that there are additional genetic, epigenetic, and environmental factors that influence the expression of the disorder, including developmental differences between the corpus callosum and corticospinal tract. Corticospinal axons and callosal axons use slightly different signaling to approach and cross midline, such that a DCC mutation may differentially affect commissural versus subcerebral axon trajectories, resulting in the variable features of mirror movements, ACC, or both. Mirror movements were consistently associated with decreased crossing of descending corticospinal tract projections at the pyramidal decussation; ACC was associated with absence of the hippocampal commissure and cingulate gyri, as well as and dysmorphic lateral ventricles. The individuals had normal to borderline intellectual disability and a more favorable outcome compared to the developmental outcomes associated with syndromic forms of ACC. <a href="#25" class="mim-tip-reference" title="Marsh, A. P. L., Heron, D., Edwards, T. J., Quartier, A., Galea, C., Nava, C., Rastetter, A., Moutard, M.-L., Anderson, V., Bitoun, P., Bunt, J., Faudet, A., and 41 others. <strong>Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance.</strong> Nature Genet. 49: 511-514, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28250454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28250454</a>] [<a href="https://doi.org/10.1038/ng.3794" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28250454">Marsh et al. (2017)</a> concluded that prenatal detection of isolated ACC related to a pathogenic DCC mutation is indicative of a lower risk of a poor neurodevelopmental outcome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28250454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 5 members of an Ethiopian Jewish family with MRMV1, <a href="#33" class="mim-tip-reference" title="Sagi-Dain, L., Kurolap, A., Ilivitzki, A., Mory, A., Paperna, T., Regeneron Genetics Center, Kedar, R., Gonzaga-Jauregui, C., Peleg, A., Feldman, H. B. <strong>A novel heterozygous loss-of-function DCC netrin 1 receptor variant in prenatal agenesis of corpus callosum and review of the literature.</strong> Am. J. Med. Genet. 182A: 205-212, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31697046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31697046</a>] [<a href="https://doi.org/10.1002/ajmg.a.61404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31697046">Sagi-Dain et al. (2020)</a> identified heterozygosity for a frameshift mutation in the DCC gene (<a href="#0012">120470.0012</a>). The mutation, which was found by whole-exome sequencing, was also identified in an asymptomatic female family member. A fetus with agenesis of the corpus callosum from a terminated pregnancy in this family was not tested for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31697046" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Familial Horizontal Gaze Palsy with Progressive Scoliosis 2 with Impaired Intellectual Development</em></strong></p><p>
|
|
In 3 patients from 2 unrelated families with familial horizontal gaze palsy with progressive scoliosis-2 with impaired intellectual development (HGPPS2; <a href="/entry/617542">617542</a>), <a href="#14" class="mim-tip-reference" title="Jamuar, S. S., Schmitz-Abe, K., D'Gama, A. M., Drottar, M., Chan, W.-M., Peeva, M., Servattalab, S., Lam, A.-T. N., Delgado, M. R., Clegg, N. J., Al Zayed, Z., Dogar, M. A., and 14 others. <strong>Biallelic mutations in human DCC cause developmental split-brain syndrome.</strong> Nature Genet. 49: 606-612, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28250456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28250456</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28250456[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/ng.3804" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28250456">Jamuar et al. (2017)</a> identified homozygous intragenic deletions in the DCC gene (<a href="#0010">120470.0010</a>-<a href="#0011">120470.0011</a>), both resulting in premature termination and functional null alleles. The deletion in the first family was found by a combination of homozygosity mapping and CNV analysis; the deletion in the second family was found by targeted sequencing of the DCC gene. The patients had agenesis of the corpus callosum, absence of the anterior and hippocampal commissures, hypoplasia of the pons and midbrain, and midline cleft throughout the brainstem, contributing to a butterfly-shaped medulla. The findings confirmed that DCC is essential for both forebrain and brainstem midline crossing in the human central nervous system. An unrelated patient with ACC and mild intellectual disability was found to have a homozygous missense variant in the DCC gene (Q691K) at a conserved residue in the third fibronectin repeat, but no clinical information was available and functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28250456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Loss of Heterozygosity in Tumors</em></strong></p><p>
|
|
In a study of 28 cases of surgically resected gastric cancer, excluding the diffuse type, <a href="#43" class="mim-tip-reference" title="Uchino, S., Tsuda, H., Noguchi, M., Yokota, J., Terada, M., Saito, T., Kobayashi, M., Sugimura, T., Hirohashi, S. <strong>Frequent loss of heterozygosity at the DCC locus in gastric cancer.</strong> Cancer Res. 52: 3099-3102, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1591722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1591722</a>]" pmid="1591722">Uchino et al. (1992)</a> concluded that loss of heterozygosity (LOH) on chromosome 18q occurs at an earlier stage than LOH on chromosome 17p and that tumor suppressor genes located on these 2 chromosome arms are critically involved in the development of most gastric cancers. Involvement of DCC may be rather selective for gastrointestinal cancers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1591722" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#13" class="mim-tip-reference" title="Hohne, M. W., Halatsch, M.-E., Kahl, G. F., Weinel, R. J. <strong>Frequent loss of expression of the potential tumor suppressor gene DCC in ductal pancreatic adenocarcinoma.</strong> Cancer Res. 52: 2616-2619, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1314700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1314700</a>]" pmid="1314700">Hohne et al. (1992)</a> presented evidence that loss of DCC gene expression is an important factor in the development or progress of pancreatic adenocarcinoma. In 8 of 11 pancreatic carcinoma cell lines and in 4 of 8 primary ductal adenocarcinomas of the pancreas, a complete extinction of DCC gene expression was observed, whereas the KRAS gene (<a href="/entry/190070">190070</a>) was mutated at codon 12 in 7 of the 8 primary tumors. Reduced or absent DCC expression tended to be associated with undifferentiated pancreatic tumor cell lines, whereas in the more differentiated ones, DCC expression was conserved. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1314700" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 panel of primary colorectal tumors, <a href="#4" class="mim-tip-reference" title="Cho, K. R., Oliner, J. D., Simons, J. W., Hedrick, L., Fearon, E. R., Preisinger, A. C., Hedge, P., Silverman, G. A., Vogelstein, B. <strong>The DCC gene: structural analysis and mutations in colorectal carcinomas.</strong> Genomics 19: 525-531, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8188295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8188295</a>] [<a href="https://doi.org/10.1006/geno.1994.1102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8188295">Cho et al. (1994)</a> found that most had lost the region containing DCC. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8188295" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The DCC protein has structural features in common with certain types of cell-adhesion molecules and may participate with other proteins in cell-cell and cell-matrix interactions. <a href="#48" class="mim-tip-reference" title="Zetter, B. R. <strong>Adhesion molecules in tumor metastasis.</strong> Semin. Cancer Biol. 4: 219-229, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8400144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8400144</a>]" pmid="8400144">Zetter (1993)</a> found that expression of the DCC gene was absent in most colorectal cancers that were metastatic to the liver, but was lost only in a minority of nonmetastatic cancers. Furthermore, <a href="#15" class="mim-tip-reference" title="Jen, J., Kim, H., Piantadosi, S., Liu, Z.-F., Levitt, R. C., Sistonen, P., Kinzler, K. W., Vogelstein, B., Hamilton, S. R. <strong>Allelic loss of chromosome 18q and prognosis in colorectal cancer.</strong> New Eng. J. Med. 331: 213-221, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8015568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8015568</a>] [<a href="https://doi.org/10.1056/NEJM199407283310401" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8015568">Jen et al. (1994)</a> found that allelic loss of 18q in the region occupied by the DCC gene carried a worse prognosis than that in cases with no loss of chromosome 18q. They developed procedures to examine the status of 18q with microsatellite markers and PCR-amplified DNA from formalin-fixed, paraffin-embedded tumors. Normal tissue and tumor tissue could be examined on the same microscopic slide. Allelic loss of 18q was assessed in 145 consecutively resected stage II or III colorectal carcinomas. The prognosis in patients with stage II cancer (Dukes stage B; tumor extending through the bowel wall, without lymph-node metastasis) was similar to that in patients with stage III cancer, who were thought to benefit from adjuvant therapy. In contrast, patients with stage II disease who did not have chromosome 18q allelic loss in their tumor had a survival rate similar to that of patients with stage I disease and might not require additional therapy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8400144+8015568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#36" class="mim-tip-reference" title="Shibata, D., Reale, M. A., Lavin, P., Silverman, M., Fearon, E. R., Steele, G., Jr., Jessup, J. M., Loda, M., Summerhayes, I. C. <strong>The DCC protein and prognosis in colorectal cancer.</strong> New Eng. J. Med. 335: 1727-1732, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8929264/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8929264</a>] [<a href="https://doi.org/10.1056/NEJM199612053352303" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8929264">Shibata et al. (1996)</a> reported findings that extended the observations of <a href="#15" class="mim-tip-reference" title="Jen, J., Kim, H., Piantadosi, S., Liu, Z.-F., Levitt, R. C., Sistonen, P., Kinzler, K. W., Vogelstein, B., Hamilton, S. R. <strong>Allelic loss of chromosome 18q and prognosis in colorectal cancer.</strong> New Eng. J. Med. 331: 213-221, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8015568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8015568</a>] [<a href="https://doi.org/10.1056/NEJM199407283310401" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8015568">Jen et al. (1994)</a>, who had found that allelic loss of 18q predicted a poor outcome in patients with stage II colorectal cancer. They studied the DCC gene as a possible specific prognostic marker. Expression of DCC was evaluated immunohistochemically in 132 paraffin-embedded samples from patients with curatively resected stage II or stage III colorectal carcinomas. They found that expression of DCC was a strong positive predictive factor for survival in both stage II and stage III colorectal carcinomas. In patients with stage II disease whose tumors expressed DCC, the 5-year survival rate was 94.3%, whereas in patients with DCC-negative tumors, the survival rate was 61.6%. In patients with stage III disease, the respective survival rates were 59.3% and 33.2%. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8929264+8015568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Maesawa, C., Tamura, G., Ogasawara, S., Suzuki, Y., Sakata, K., Sugimura, J., Nishizuka, S., Sato, N., Ishida, K., Saito, K., Satodate, R. <strong>Loss of heterozygosity at the DCC gene locus is not crucial for the acquisition of metastatic potential in oesophageal squamous cell carcinoma.</strong> Europ. J. Cancer. 32A: 896-898, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9081374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9081374</a>] [<a href="https://doi.org/10.1016/0959-8049(96)00010-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9081374">Maesawa et al. (1996)</a> screened tumor specimens from 111 patients with esophageal squamous cell carcinoma for LOH at the DCC locus and observed LOH in 10 of 61 informative cases (16%). No statistically significant correlation was observed between DCC-LOH and lymph node metastasis, histopathologic grade, or tumor stage. Survivorship of DCC-LOH patients was not statistically different from that of patients without LOH. These results suggested to <a href="#24" class="mim-tip-reference" title="Maesawa, C., Tamura, G., Ogasawara, S., Suzuki, Y., Sakata, K., Sugimura, J., Nishizuka, S., Sato, N., Ishida, K., Saito, K., Satodate, R. <strong>Loss of heterozygosity at the DCC gene locus is not crucial for the acquisition of metastatic potential in oesophageal squamous cell carcinoma.</strong> Europ. J. Cancer. 32A: 896-898, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9081374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9081374</a>] [<a href="https://doi.org/10.1016/0959-8049(96)00010-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9081374">Maesawa et al. (1996)</a> that LOH at the DCC locus is not related to the acquisition of metastatic potential or the state of tumor cell differentiation in esophageal squamous cell carcinoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9081374" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Somatic Mutations</em></strong></p><p>
|
|
<a href="#4" class="mim-tip-reference" title="Cho, K. R., Oliner, J. D., Simons, J. W., Hedrick, L., Fearon, E. R., Preisinger, A. C., Hedge, P., Silverman, G. A., Vogelstein, B. <strong>The DCC gene: structural analysis and mutations in colorectal carcinomas.</strong> Genomics 19: 525-531, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8188295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8188295</a>] [<a href="https://doi.org/10.1006/geno.1994.1102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8188295">Cho et al. (1994)</a> found a somatic missense mutation in a colorectal tumor (<a href="#0001">120470.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8188295" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Miyake, S., Nagai, K., Yoshino, K., Oto, M., Endo, M., Yuasa, Y. <strong>Point mutations and allelic deletion of tumor suppressor gene DCC in human esophageal squamous cell carcinomas and their relation to metastasis.</strong> Cancer Res. 54: 3007-3010, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8187090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8187090</a>]" pmid="8187090">Miyake et al. (1994)</a> identified somatic missense mutations and loss of heterozygosity in esophageal tumors (see <a href="#0002">120470.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8187090" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 exome sequencing, <a href="#46" class="mim-tip-reference" title="Wei, X., Walia, V., Lin, J. C., Teer, J. K., Prickett, T. D., Gartner, J., Davis, S., NISC Comparative Sequencing Program, Stemke-Hale, K., Davies, M. A., Gershenwald, J. E., Robinson, W., Robinson, S., Rosenberg, S. A., Samuels, Y. <strong>Exome sequencing identifies GRIN2A as frequently mutated in melanoma.</strong> Nature Genet. 43: 442-446, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21499247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21499247</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21499247[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/ng.810" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21499247">Wei et al. (2011)</a> identified a recurrent somatic gly55-to-glu (G55E) mutation in the DCC gene in 3 (2%) of 167 melanoma (see <a href="/entry/155600">155600</a>) samples. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21499247" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
For discussion of a possible association between variation in the DCC gene and hypogonadotropic hypogonadism, see <a href="/entry/147950">147950</a>.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#9" class="mim-tip-reference" title="Finger, J. H., Bronson, R. T., Harris, B., Johnson, K., Przyborski, S. A., Ackerman, S. L. <strong>The Netrin 1 receptors Unc5h3 and Dcc are necessary at multiple choice points for the guidance of corticospinal tract axons.</strong> J. Neurosci. 22: 10346-10356, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12451134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12451134</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12451134[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/10.1523/JNEUROSCI.22-23-10346.2002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12451134">Finger et al. (2002)</a> described a spontaneous mutation in mice, 'kanga,' that resulted in mild to severe inability to maintain an upright position. Mutant mice often moved their hind legs in a concerted manner, resulting in a somewhat hopping gait. <a href="#9" class="mim-tip-reference" title="Finger, J. H., Bronson, R. T., Harris, B., Johnson, K., Przyborski, S. A., Ackerman, S. L. <strong>The Netrin 1 receptors Unc5h3 and Dcc are necessary at multiple choice points for the guidance of corticospinal tract axons.</strong> J. Neurosci. 22: 10346-10356, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12451134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12451134</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12451134[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/10.1523/JNEUROSCI.22-23-10346.2002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12451134">Finger et al. (2002)</a> found that the kanga phenotype results from deletion of exon 29 of the Dcc gene. Immunohistochemical analysis revealed that the corticospinal tract of kanga/kanga mice showed abnormalities at the pyramidal decussation. While homozygous mutation of the Dcc gene disrupted the decussation of all corticospinal tract axons, in Unc5h3 (<a href="/entry/603610">603610</a>)-mutant mice corticospinal tract fibers that crossed the midline were found in the contralateral lateral funiculus but not the ventral funiculus. <a href="#9" class="mim-tip-reference" title="Finger, J. H., Bronson, R. T., Harris, B., Johnson, K., Przyborski, S. A., Ackerman, S. L. <strong>The Netrin 1 receptors Unc5h3 and Dcc are necessary at multiple choice points for the guidance of corticospinal tract axons.</strong> J. Neurosci. 22: 10346-10356, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12451134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12451134</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12451134[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/10.1523/JNEUROSCI.22-23-10346.2002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12451134">Finger et al. (2002)</a> also found that Unc5h3 and Dcc act synergistically in guiding corticospinal tract axons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12451134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 help elucidate the functions of the DCC gene and to test the suggestion that it functions as a receptor for the axonal chemoattractant netrin-1, <a href="#7" class="mim-tip-reference" title="Fazeli, A., Dickinson, S. L., Hermiston, M. L., Tighe, R. V., Steen, R. G., Small, C. G., Stoeckli, E. T., Keino-Masu, K., Masu, M., Rayburn, H., Simons, J., Bronson, R. T., Gordon, J. I., Tessier-Lavigne, M., Weinberg, R. A. <strong>Phenotype of mice lacking functional Deleted in colorectal cancer (Dcc) gene.</strong> Nature 386: 796-804, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9126737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9126737</a>] [<a href="https://doi.org/10.1038/386796a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9126737">Fazeli et al. (1997)</a> inactivated the DCC homolog in the mouse genome through use of homologous recombination and studied the effects of this inactivation on both the intestine and the developing nervous system. They found defects in axonal projections that were similar to those observed in netrin-1-deficient mice, but there was no effect on growth, differentiation, morphogenesis, or tumorigenesis in mouse intestine. These observations failed to support a tumor-suppressor function for DCC in the mouse, but were consistent with the hypothesis that DCC is a component of the receptor for netrin-1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9126737" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 wildtype and Dcc -/- mouse embryos, <a href="#35" class="mim-tip-reference" title="Shi, M., Guo, C., Dai, J.-X., Ding, Y.-Q. <strong>DCC is required for the tangential migration of noradrenergic neurons in locus coeruleus of mouse brain.</strong> Molec. Cell. Neurosci. 39: 529-538, 2008. Note: Erratum: Molec. Cell. Neurosci. 45: 84 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18771734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18771734</a>] [<a href="https://doi.org/10.1016/j.mcn.2008.07.023" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18771734">Shi et al. (2008)</a> found that Dcc was expressed in neurons of the locus ceruleus and that Dcc was required for normal locus ceruleus development. Locus ceruleus-specific gene expression was normal in Dcc-null embryos, but the initiation of tangential migration of locus ceruleus neurons was delayed. Subsequently, locus ceruleus neurons in Dcc-null mice were misdirected to the pons or ectopically located in the cerebellum. Migration of locus ceruleus neurons and the morphology of the locus ceruleus was not compromised in kanga/kanga mice, demonstrating that the C-terminal domain required for commissural axon guidance is not necessary for the proper development of the locus ceruleus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18771734" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 role of DCC-induced apoptosis in the control of tumor progression, <a href="#2" class="mim-tip-reference" title="Castets, M., Broutier, L., Molin, Y., Brevet, M., Chazot, G., Gadot, N., Paquet, A., Mazelin, L., Jarroson-Wuilleme, L., Scoazec, J.-Y., Bernet, A., Mehlen, P. <strong>DCC constrains tumour progression via its dependence receptor activity.</strong> Nature 482: 534-537, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22158121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22158121</a>] [<a href="https://doi.org/10.1038/nature10708" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22158121">Castets et al. (2011)</a> created a mouse model in which the proapoptotic activity of DCC is genetically silenced. Although the loss of DCC-induced apoptosis in this mouse model was not associated with a major disorganization of the intestines, it led to spontaneous intestinal neoplasia at a relatively low frequency. Loss of DCC-induced apoptosis was also associated with an increase in the number and aggressiveness of intestinal tumors in a predisposing APC (<a href="/entry/611731">611731</a>) mutant context, resulting in the development of highly invasive adenocarcinomas. <a href="#2" class="mim-tip-reference" title="Castets, M., Broutier, L., Molin, Y., Brevet, M., Chazot, G., Gadot, N., Paquet, A., Mazelin, L., Jarroson-Wuilleme, L., Scoazec, J.-Y., Bernet, A., Mehlen, P. <strong>DCC constrains tumour progression via its dependence receptor activity.</strong> Nature 482: 534-537, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22158121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22158121</a>] [<a href="https://doi.org/10.1038/nature10708" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22158121">Castets et al. (2011)</a> concluded that DCC functions as a tumor suppressor via its ability to trigger tumor cell apoptosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22158121" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Krimpenfort, P., Song, J.-Y., Proost, N., Zevenhoven, J., Jonkers, J., Berns, A. <strong>Deleted in colorectal carcinoma suppresses metastasis in p53-deficient mammary tumours.</strong> Nature 482: 538-541, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22358843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22358843</a>] [<a href="https://doi.org/10.1038/nature10790" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22358843">Krimpenfort et al. (2012)</a> showed that in a mouse model of mammary carcinoma based on somatic inactivation of p53 (<a href="/entry/191170">191170</a>), additional loss of DCC promotes metastasis formation without affecting the primary tumor phenotype. Furthermore, they demonstrated that in cell cultures derived from p53-deficient mouse mammary tumors, DCC expression controls netrin-1 (<a href="/entry/601614">601614</a>)-dependent cell survival, providing a mechanistic basis for the enhanced metastatic capacity of tumor cells lacking DCC. Consistent with this idea, in vivo tumor cell survival is enhanced by DCC loss. <a href="#20" class="mim-tip-reference" title="Krimpenfort, P., Song, J.-Y., Proost, N., Zevenhoven, J., Jonkers, J., Berns, A. <strong>Deleted in colorectal carcinoma suppresses metastasis in p53-deficient mammary tumours.</strong> Nature 482: 538-541, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22358843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22358843</a>] [<a href="https://doi.org/10.1038/nature10790" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22358843">Krimpenfort et al. (2012)</a> concluded that their data supported the function of DCC as a context-dependent tumor suppressor that limits survival of disseminated tumor cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22358843" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="history" class="mim-anchor"></a>
|
|
<h4 href="#mimHistoryFold" id="mimHistoryToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimHistoryToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimHistoryFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>It is of interest that <a href="#23" class="mim-tip-reference" title="Lynch, H. T., Schuelke, G. S., Kimberling, W. J., Albano, W. A., Lynch, J. F., Biscone, K. A., Lipkin, M. L., Deschner, E. E., Mikol, Y. B., Sandberg, A. A., Elston, R. C., Bailey-Wilson, J. E., Danes, B. S. <strong>Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). II. Biomarker studies.</strong> Cancer 56: 939-951, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4016686/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4016686</a>] [<a href="https://doi.org/10.1002/1097-0142(19850815)56:4<939::aid-cncr2820560440>3.0.co;2-t" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4016686">Lynch et al. (1985)</a> found a lod score of 3.19 for linkage between a familial cancer syndrome (Lynch syndrome II; <a href="/entry/120435">120435</a>) and Kidd blood group (JK; <a href="/entry/111000">111000</a>); the Kidd blood group has been assigned to 18q11-q12. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4016686" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Bowman, B. M., Wildrick, D. M., Alfaro, S. R. <strong>Chromosome 18 allele loss at the D18S6 locus in human colorectal carcinomas.</strong> Biochem. Biophys. Res. Commun. 155: 463-469, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3415702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3415702</a>] [<a href="https://doi.org/10.1016/s0006-291x(88)81109-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3415702">Bowman et al. (1988)</a> found tumor-specific allele loss at the D18S6 locus on chromosome 18 in 2 patients with familial adenomatous polyposis and in 2 patients with sporadic colon cancer. D18S6 is closely linked to LCFS2 and JK. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3415702" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#40" class="mim-tip-reference" title="Tanaka, K., Oshimura, M., Kikuchi, R., Seki, M., Hayashi, T., Miyaki, M. <strong>Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 5 or 18.</strong> Nature 349: 340-342, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1670965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1670965</a>] [<a href="https://doi.org/10.1038/349340a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1670965">Tanaka et al. (1991)</a> demonstrated that transfer of a normal human chromosome 18 into a colon carcinoma cell line through microcell hybridization severely reduced the cloning efficiency of the hybrid cells in soft agar and completely suppressed tumorigenicity in athymic nude mice. Similar results were obtained when a normal chromosome 5, which carries the locus for adenomatous polyposis coli (<a href="/entry/611731">611731</a>), was transferred into the cells, but the growth properties of the hybrid cells were unchanged when chromosome 11 was introduced. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1670965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Nigro, J. M., Cho, K. R., Fearon, E. R., Kern, S. E., Ruppert, J. M., Oliner, J. D., Kinzler, K. W., Vogelstein, B. <strong>Scrambled exons.</strong> Cell 64: 607-613, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1991322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1991322</a>] [<a href="https://doi.org/10.1016/0092-8674(91)90244-s" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1991322">Nigro et al. (1991)</a> observed a curious phenomenon of scrambled exons in the DCC gene in a variety of normal and neoplastic cells of rodent and human origin. Abnormally spliced transcripts showed that exons were joined accurately at consensus splice sites, but in an order different from that present in the primary transcript. Thus, a novel type of RNA product resulted. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1991322" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>12 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/120470" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=120470[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 COLORECTAL CANCER, SOMATIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DCC, PRO-HIS, 4124C-A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs387906555 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906555;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/rs387906555?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=rs387906555" 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=rs387906555" 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=RCV000018603" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018603" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018603</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>To look for structural alterations of the DCC gene, <a href="#4" class="mim-tip-reference" title="Cho, K. R., Oliner, J. D., Simons, J. W., Hedrick, L., Fearon, E. R., Preisinger, A. C., Hedge, P., Silverman, G. A., Vogelstein, B. <strong>The DCC gene: structural analysis and mutations in colorectal carcinomas.</strong> Genomics 19: 525-531, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8188295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8188295</a>] [<a href="https://doi.org/10.1006/geno.1994.1102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8188295">Cho et al. (1994)</a> analyzed 60 colorectal cancers matched with normal DNA samples from the same individual, using Southern blot hybridization to DCC cDNA probes. In 1 tumor, an altered pattern of EcoRI fragments was found and shown to have its basis in a somatically acquired point mutation in intron 13. The sequences flanking the mutation had features suggestive of an exon, including a short open reading frame and consensus splice acceptor and donor sites. These findings suggested that the tumor contained a mutation in an alternatively utilized exon. To search for more subtle alterations, <a href="#4" class="mim-tip-reference" title="Cho, K. R., Oliner, J. D., Simons, J. W., Hedrick, L., Fearon, E. R., Preisinger, A. C., Hedge, P., Silverman, G. A., Vogelstein, B. <strong>The DCC gene: structural analysis and mutations in colorectal carcinomas.</strong> Genomics 19: 525-531, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8188295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8188295</a>] [<a href="https://doi.org/10.1006/geno.1994.1102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8188295">Cho et al. (1994)</a> evaluated several exons and their flanking intron sequences for the presence of mutations in 30 colorectal cancers by an RNase protection assay. A C-to-A transversion at position 4124 in exon 28 was identified in 1 tumor. This mutation was predicted to result in a nonconservative amino acid change from proline to histidine. It was absent from the DNA of normal lymphocytes from the same patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8188295" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ESOPHAGEAL CARCINOMA, SOMATIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DCC, MET168THR
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121912967 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912967;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=rs121912967" 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=rs121912967" 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=RCV000018604" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000018604" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000018604</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Since the tumor suppressor gene DCC shows amino acid sequence homology to the neural cell adhesion molecule (<a href="/entry/116930">116930</a>), <a href="#29" class="mim-tip-reference" title="Miyake, S., Nagai, K., Yoshino, K., Oto, M., Endo, M., Yuasa, Y. <strong>Point mutations and allelic deletion of tumor suppressor gene DCC in human esophageal squamous cell carcinomas and their relation to metastasis.</strong> Cancer Res. 54: 3007-3010, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8187090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8187090</a>]" pmid="8187090">Miyake et al. (1994)</a> considered the possibility that DCC might be related to tumor metastasis. They examined 51 cases of primary esophageal carcinoma for point mutations and loss of the gene. By screening using PCR-single strand conformation polymorphism analysis, they found point mutations in 2 cases. One case with lymph node metastasis showed an ATG-(met)-to-ACC-(thr) missense mutation in codon 168. Another case showed a CGA (arg)-to-GGA (gly) mutation in codon 201, which might be a polymorphic change, and 2 other mutations resulting in no amino acid change. Forty-four of the 51 cases (86%) were informative for loss of heterozygosity of the DCC gene; of these, 10 (23%) showed allelic deletion. The further away the lymph node metastasis was from the primary tumor, the higher the frequency of allelic deletions. They also found allelic deletions in moderately and poorly differentiated squamous cell carcinomas but not in well-differentiated ones. They interpreted these findings to indicate that alterations in the DCC gene are related to the degree of lymph node metastasis and the degree of differentiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8187090" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MIRROR MOVEMENTS 1 AND/OR AGENESIS OF THE CORPUS CALLOSUM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DCC, IVS6DS, 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">rs797044553 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797044553;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=rs797044553" 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=rs797044553" 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=RCV000192080 OR RCV003441766" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000192080, RCV003441766" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000192080...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a large 4-generation French Canadian family segregating autosomal dominant congenital mirror movements (MRMV1; <a href="/entry/157600">157600</a>) with incomplete penetrance, <a href="#37" class="mim-tip-reference" title="Srour, M., Riviere, J.-B., Pham, J. M. T., Dube, M.-P., Girard, S., Morin, S., Dion, P. A., Asselin, G., Rochefort, D., Hince, P., Diab, S., Sharafaddinzadeh, N., Chouinard, S., Theoret, H., Charron, F., Rouleau, G. A. <strong>Mutations in DCC cause congenital mirror movements.</strong> Science 328: 592 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20431009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20431009</a>] [<a href="https://doi.org/10.1126/science.1186463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20431009">Srour et al. (2010)</a> identified a G-to-A transition at nucleotide 1140 of the DCC gene, at the splice donor site of intron 6 (1140+1G-A). This mutation led to skipping of exon 6 and a frameshift after amino acid 329 with the introduction of a stop codon 15 amino acids further down the new reading frame (Val329GlyfsTer15). This mutation segregated with the risk haplotype and was not found in 760 unrelated Caucasian controls, including 512 French Canadians. Copy number variation analysis in 315 French Canadian controls did not reveal any structural variations encompassing DCC exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20431009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MIRROR MOVEMENTS 1 AND/OR AGENESIS OF THE CORPUS CALLOSUM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DCC, 1-BP INS, 571G
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs797044552 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797044552;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=rs797044552" 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=rs797044552" 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=RCV000192078" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000192078" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000192078</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 5-generation Iranian family with congenital mirror movements (MRMV1; <a href="/entry/157600">157600</a>), initially described by <a href="#34" class="mim-tip-reference" title="Sharafaddinzadeh, N., Bavarsad, R., Yousefkhah, M., Aleali, A. M. <strong>Familial mirror movements over five generations. (Letter)</strong> Neurology India 56: 482-483, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19127048/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19127048</a>] [<a href="https://doi.org/10.4103/0028-3886.44813" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19127048">Sharafaddinzadeh et al. (2008)</a>, <a href="#37" class="mim-tip-reference" title="Srour, M., Riviere, J.-B., Pham, J. M. T., Dube, M.-P., Girard, S., Morin, S., Dion, P. A., Asselin, G., Rochefort, D., Hince, P., Diab, S., Sharafaddinzadeh, N., Chouinard, S., Theoret, H., Charron, F., Rouleau, G. A. <strong>Mutations in DCC cause congenital mirror movements.</strong> Science 328: 592 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20431009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20431009</a>] [<a href="https://doi.org/10.1126/science.1186463" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20431009">Srour et al. (2010)</a> identified insertion of a guanine at nucleotide 571 in exon 3 of the DCC gene, resulting in frameshift with a termination codon 35 amino acids later (571dupG; Val191GlyfsTer35). This mutation was absent in 538 unrelated control individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20431009+19127048" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MIRROR MOVEMENTS 1 AND/OR AGENESIS OF THE CORPUS CALLOSUM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DCC, 2-BP DEL, 3835CT
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs797044556 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797044556;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=rs797044556" 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=rs797044556" 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=RCV000192083" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000192083" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000192083</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 affected members of a 3-generation Italian family with congenital mirror movements (MRMV1; <a href="/entry/157600">157600</a>), <a href="#6" class="mim-tip-reference" title="Depienne, C., Cincotta, M., Billot, S., Bouteiller, D., Groppa, S., Brochard, V., Flamand, C., Hubsch, C., Meunier, S., Giovannelli, F., Klebe, S., Corvol, J. C., Vidailhet, M., Brice, A., Roze, E. <strong>A novel DCC mutation and genetic heterogeneity in congenital mirror movements.</strong> Neurology 76: 260-264, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21242494/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21242494</a>] [<a href="https://doi.org/10.1212/WNL.0b013e318207b1e0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21242494">Depienne et al. (2011)</a> identified a heterozygous 2-bp deletion (3835delCT) in exon 26 of the DCC gene, resulting in a frameshift and premature termination. The patients had onset in infancy or early childhood of involuntary mirror movements affecting the upper limbs and hands. Three had a stable condition; 1 had mild improvement during childhood. The mutation likely resulted in nonsense-mediated mRNA decay and haploinsufficiency. The mutation was not found in 340 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21242494" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MIRROR MOVEMENTS 1 AND/OR AGENESIS OF THE CORPUS CALLOSUM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DCC, ARG275TER
|
|
</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> rs754914260 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs754914260;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/rs754914260?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=rs754914260" 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=rs754914260" 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=RCV000192079 OR RCV000416354 OR RCV004546447" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000192079, RCV000416354, RCV004546447" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000192079...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 7 members of a 3-generation family (family 3) with congenital mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; <a href="/entry/157600">157600</a>), <a href="#25" class="mim-tip-reference" title="Marsh, A. P. L., Heron, D., Edwards, T. J., Quartier, A., Galea, C., Nava, C., Rastetter, A., Moutard, M.-L., Anderson, V., Bitoun, P., Bunt, J., Faudet, A., and 41 others. <strong>Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance.</strong> Nature Genet. 49: 511-514, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28250454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28250454</a>] [<a href="https://doi.org/10.1038/ng.3794" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28250454">Marsh et al. (2017)</a> identified a heterozygous c.823C-T transition (c.823C-T, NM_005215.3) in the DCC gene, resulting in an arg275-to-ter (R275X) substitution in the N-terminal extracellular domain. The mutation was not found in the dbSNP, 1000 Genomes Project, or ExAC databases. The family was originally reported by <a href="#28" class="mim-tip-reference" title="Meneret, A., Depienne, C., Riant, F., Trouillard, O., Bouteiller, D., Cincotta, M., Bitoun, P., Wickert, J., Lagroua, I., Westenberger, A., Borgheresi, A., Doummar, D., and 18 others. <strong>Congenital mirror movements: mutational analysis of RAD51 and DCC in 26 cases.</strong> Neurology 82: 1999-2002, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24808016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24808016</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24808016[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/10.1212/WNL.0000000000000477" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24808016">Meneret et al. (2014)</a> as having congenital mirror movements, but was not described in detail. According to the pedigree provided by <a href="#25" class="mim-tip-reference" title="Marsh, A. P. L., Heron, D., Edwards, T. J., Quartier, A., Galea, C., Nava, C., Rastetter, A., Moutard, M.-L., Anderson, V., Bitoun, P., Bunt, J., Faudet, A., and 41 others. <strong>Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance.</strong> Nature Genet. 49: 511-514, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28250454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28250454</a>] [<a href="https://doi.org/10.1038/ng.3794" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28250454">Marsh et al. (2017)</a>, there were 7 confirmed mutation carriers in the family, including 2 (a male and female) with mirror movements and partial ACC, 3 (2 males and a female) with isolated mirror movements with normal brain imaging, 1 female with complete ACC and without mirror movements, and 1 unaffected female mutation carrier, indicating incomplete penetrance. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=24808016+28250454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MIRROR MOVEMENTS 1 AND/OR AGENESIS OF THE CORPUS CALLOSUM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DCC, 1-BP DEL, 925A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1057519053 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1057519053;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=rs1057519053" 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=rs1057519053" 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=RCV000416317 OR RCV000494695" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000416317, RCV000494695" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000416317...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a large multigenerational family (family 1) with congenital mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; <a href="/entry/157600">157600</a>), <a href="#25" class="mim-tip-reference" title="Marsh, A. P. L., Heron, D., Edwards, T. J., Quartier, A., Galea, C., Nava, C., Rastetter, A., Moutard, M.-L., Anderson, V., Bitoun, P., Bunt, J., Faudet, A., and 41 others. <strong>Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance.</strong> Nature Genet. 49: 511-514, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28250454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28250454</a>] [<a href="https://doi.org/10.1038/ng.3794" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28250454">Marsh et al. (2017)</a> identified a heterozygous 1-bp deletion (c.925delA, NM_005215.3) in the DCC gene, resulting in a frameshift and premature termination (Thr309ProfsTer26) in the N-terminal extracellular domain. The mutation, which was found by a combination of linkage analysis and exome sequencing, was confirmed by Sanger sequencing. It was not found in the dbSNP, 1000 Genomes Project, or ExAC databases. The mutation segregated with the disorder in the family, but there was evidence of incomplete penetrance. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28250454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MIRROR MOVEMENTS 1 AND/OR AGENESIS OF THE CORPUS CALLOSUM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DCC, VAL793GLY
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1057519054 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1057519054;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=rs1057519054" 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=rs1057519054" 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=RCV000416336 OR RCV000494699" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000416336, RCV000494699" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000416336...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a 3-generation family (family 2) with congenital mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; <a href="/entry/157600">157600</a>), <a href="#25" class="mim-tip-reference" title="Marsh, A. P. L., Heron, D., Edwards, T. J., Quartier, A., Galea, C., Nava, C., Rastetter, A., Moutard, M.-L., Anderson, V., Bitoun, P., Bunt, J., Faudet, A., and 41 others. <strong>Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance.</strong> Nature Genet. 49: 511-514, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28250454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28250454</a>] [<a href="https://doi.org/10.1038/ng.3794" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28250454">Marsh et al. (2017)</a> identified a heterozygous c.2378T-G transversion (c.2378T-G, NM_005215.3) in the DCC gene, resulting in a val793-to-gly (V793G) substitution in the netrin-1 binding domain. The mutation, which was found by a combination of linkage analysis and exome sequencing, was confirmed by Sanger sequencing. It was not found in the dbSNP, 1000 Genomes Project, or ExAC databases. The mutation segregated with the disorder in the family, but there was evidence of incomplete penetrance. Functional studies of the variant and studies of patient cells were not performed, but the mutation was predicted to be disruptive. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28250454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MIRROR MOVEMENTS 1 AND/OR AGENESIS OF THE CORPUS CALLOSUM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DCC, GLY805GLU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1057519055 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1057519055;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=rs1057519055" 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=rs1057519055" 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=RCV000416322 OR RCV000494701" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000416322, RCV000494701" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000416322...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 members of a 3-generation family (family 4) with congenital mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; <a href="/entry/157600">157600</a>), <a href="#25" class="mim-tip-reference" title="Marsh, A. P. L., Heron, D., Edwards, T. J., Quartier, A., Galea, C., Nava, C., Rastetter, A., Moutard, M.-L., Anderson, V., Bitoun, P., Bunt, J., Faudet, A., and 41 others. <strong>Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance.</strong> Nature Genet. 49: 511-514, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28250454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28250454</a>] [<a href="https://doi.org/10.1038/ng.3794" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28250454">Marsh et al. (2017)</a> identified a heterozygous c.2414G-A transition (c.2414G-A, NM_005215.3) in the DCC gene, resulting in a gly805-to-glu (G805E) substitution in the netrin-1 binding domain. The mutation was found by direct sequencing and was not present in the dbSNP, 1000 Genomes Project, or ExAC databases. The mutation segregated with the disorder in the family, but there was evidence of incomplete penetrance. Functional studies of the variant and studies of patient cells were not performed, but the mutation was predicted to be disruptive. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28250454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 GAZE PALSY, FAMILIAL HORIZONTAL, WITH PROGRESSIVE SCOLIOSIS 2, WITH IMPAIRED INTELLECTUAL DEVELOPMENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DCC, 7,682-BP DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000494694" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000494694" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000494694</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers, born of Mexican parents, with familial horizontal gaze palsy with progressive scoliosis-2 with impaired intellectual development (HGPPS2; <a href="/entry/617542">617542</a>), <a href="#14" class="mim-tip-reference" title="Jamuar, S. S., Schmitz-Abe, K., D'Gama, A. M., Drottar, M., Chan, W.-M., Peeva, M., Servattalab, S., Lam, A.-T. N., Delgado, M. R., Clegg, N. J., Al Zayed, Z., Dogar, M. A., and 14 others. <strong>Biallelic mutations in human DCC cause developmental split-brain syndrome.</strong> Nature Genet. 49: 606-612, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28250456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28250456</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28250456[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/ng.3804" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28250456">Jamuar et al. (2017)</a> identified a homozygous 7,682-bp deletion (chr18.49,867,185-49,874,867del, GRCh37) affecting exon 1 and intron 1 of the DCC gene. Analysis of patient cells showed that the deletion resulting in the skipping of exon 1, a frameshift, and premature termination (Pro11ThrfsTer15), resulting in a functional null allele. The deletion, which was found by a combination of homozygosity mapping and CNV analysis, was not found in the dbSNP (build 146), 1000 Genomes Project, ExAC, or Exome Variant Server databases, or in an internal exome database. The mother was a heterozygous carrier; DNA from the father was unavailable. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28250456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 GAZE PALSY, FAMILIAL HORIZONTAL, WITH PROGRESSIVE SCOLIOSIS 2, WITH IMPAIRED INTELLECTUAL DEVELOPMENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DCC, 7-BP DEL, NT788
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1555682265 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555682265;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=rs1555682265" 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=rs1555682265" 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=RCV000494700" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000494700" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000494700</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a girl, born of consanguineous Saudi Arabian parents, with familial horizontal gaze palsy with progressive scoliosis-2 with impaired intellectual development (HGPPS2; <a href="/entry/617542">617542</a>), <a href="#14" class="mim-tip-reference" title="Jamuar, S. S., Schmitz-Abe, K., D'Gama, A. M., Drottar, M., Chan, W.-M., Peeva, M., Servattalab, S., Lam, A.-T. N., Delgado, M. R., Clegg, N. J., Al Zayed, Z., Dogar, M. A., and 14 others. <strong>Biallelic mutations in human DCC cause developmental split-brain syndrome.</strong> Nature Genet. 49: 606-612, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28250456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28250456</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28250456[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/ng.3804" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28250456">Jamuar et al. (2017)</a> identified a homozygous 7-bp deletion (chr18.50,450,167-50,450,173del, GRCh37) in exon 4 of the DCC gene, resulting in a frameshift and premature termination (Val263AlafsTer36) and a functional null allele. The deletion, which was found by targeted sequencing of the DCC gene, was present in the heterozygous state in each parent, but was not found in the dbSNP (build 146), 1000 Genomes Project, ExAC, or Exome Variant Server databases, or in an internal exome database of over 1,000 samples from Middle Eastern individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28250456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MIRROR MOVEMENTS 1 AND/OR AGENESIS OF THE CORPUS CALLOSUM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DCC, 1-BP DUP, 2774A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2145024323 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2145024323;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=rs2145024323" 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=rs2145024323" 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=RCV001731260" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001731260" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001731260</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 patients from 2 generations of an Ethiopian Jewish family with congenital mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; <a href="/entry/157600">157600</a>), <a href="#33" class="mim-tip-reference" title="Sagi-Dain, L., Kurolap, A., Ilivitzki, A., Mory, A., Paperna, T., Regeneron Genetics Center, Kedar, R., Gonzaga-Jauregui, C., Peleg, A., Feldman, H. B. <strong>A novel heterozygous loss-of-function DCC netrin 1 receptor variant in prenatal agenesis of corpus callosum and review of the literature.</strong> Am. J. Med. Genet. 182A: 205-212, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31697046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31697046</a>] [<a href="https://doi.org/10.1002/ajmg.a.61404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31697046">Sagi-Dain et al. (2020)</a> identified heterozygosity for a 1-bp duplication (c.2774dupA, NM_005215) in the DCC gene, predicted to result in a frameshift and premature termination (Asn925LysfsTer17). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. The mutation was also identified in an asymptomatic female family member. A fetus with agenesis of the corpus callosum from a terminated pregnancy in this family was not tested for the mutation. The mutation was not present in the dbSNP or gnomAD databases or in an in-house database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31697046" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Bowman1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bowman, B. M., Wildrick, D. M., Alfaro, S. R.
|
|
<strong>Chromosome 18 allele loss at the D18S6 locus in human colorectal carcinomas.</strong>
|
|
Biochem. Biophys. Res. Commun. 155: 463-469, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3415702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3415702</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3415702" target="_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/s0006-291x(88)81109-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Castets2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Castets, M., Broutier, L., Molin, Y., Brevet, M., Chazot, G., Gadot, N., Paquet, A., Mazelin, L., Jarroson-Wuilleme, L., Scoazec, J.-Y., Bernet, A., Mehlen, P.
|
|
<strong>DCC constrains tumour progression via its dependence receptor activity.</strong>
|
|
Nature 482: 534-537, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22158121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22158121</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22158121" target="_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/nature10708" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Chan1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chan, S. S.-Y., Zheng, H., Su, M.-W., Wilk, R., Killeen, M. T., Hedgecock, E. M., Culotti, J. G.
|
|
<strong>UNC-40, a C. elegans homolog of the DCC (deleted in colorectal cancer), is required in motile cells responding to UNC-6 netrin cues.</strong>
|
|
Cell 87: 187-195, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8861903/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8861903</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8861903" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0092-8674(00)81337-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Cho1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cho, K. R., Oliner, J. D., Simons, J. W., Hedrick, L., Fearon, E. R., Preisinger, A. C., Hedge, P., Silverman, G. A., Vogelstein, B.
|
|
<strong>The DCC gene: structural analysis and mutations in colorectal carcinomas.</strong>
|
|
Genomics 19: 525-531, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8188295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8188295</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8188295" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1994.1102" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Colon-Ramos2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Colon-Ramos, D. A., Margeta, M. A., Shen, K.
|
|
<strong>Glia promote local synaptogenesis through UNC-6 (netrin) signaling in C. elegans.</strong>
|
|
Science 318: 103-106, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17916735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17916735</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17916735[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=17916735" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1143762" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Depienne2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Depienne, C., Cincotta, M., Billot, S., Bouteiller, D., Groppa, S., Brochard, V., Flamand, C., Hubsch, C., Meunier, S., Giovannelli, F., Klebe, S., Corvol, J. C., Vidailhet, M., Brice, A., Roze, E.
|
|
<strong>A novel DCC mutation and genetic heterogeneity in congenital mirror movements.</strong>
|
|
Neurology 76: 260-264, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21242494/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21242494</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21242494" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/WNL.0b013e318207b1e0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Fazeli1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fazeli, A., Dickinson, S. L., Hermiston, M. L., Tighe, R. V., Steen, R. G., Small, C. G., Stoeckli, E. T., Keino-Masu, K., Masu, M., Rayburn, H., Simons, J., Bronson, R. T., Gordon, J. I., Tessier-Lavigne, M., Weinberg, R. A.
|
|
<strong>Phenotype of mice lacking functional Deleted in colorectal cancer (Dcc) gene.</strong>
|
|
Nature 386: 796-804, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9126737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9126737</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9126737" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/386796a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Fearon1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fearon, E. R., Cho, K. R., Nigro, J. M., Kern, S. E., Simons, J. W., Ruppert, J. M., Hamilton, S. R., Preisinger, A. C., Thomas, G., Kinzler, K. W., Vogelstein, B.
|
|
<strong>Identification of a chromosome 18q gene that is altered in colorectal cancers.</strong>
|
|
Science 247: 49-56, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2294591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2294591</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2294591" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.2294591" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Finger2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Finger, J. H., Bronson, R. T., Harris, B., Johnson, K., Przyborski, S. A., Ackerman, S. L.
|
|
<strong>The Netrin 1 receptors Unc5h3 and Dcc are necessary at multiple choice points for the guidance of corticospinal tract axons.</strong>
|
|
J. Neurosci. 22: 10346-10356, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12451134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12451134</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12451134[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=12451134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1523/JNEUROSCI.22-23-10346.2002" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Forcet2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Forcet, C., Stein, E., Pays, L., Corset, V., Llambi, F., Tessier-Lavigne, M., Mehlen, P.
|
|
<strong>Netrin-1-mediated axon outgrowth requires deleted in colorectal cancer-dependent MAPK activation.</strong>
|
|
Nature 417: 443-447, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11986622/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11986622</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11986622" target="_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/nature748" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Galko2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Galko, M. J., Tessier-Lavigne, M.
|
|
<strong>Function of an axonal chemoattractant modulated by metalloprotease activity.</strong>
|
|
Science 289: 1365-1367, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10958786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10958786</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10958786" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.289.5483.1365" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Gotley1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gotley, D. C., Reeder, J. A., Fawcett, J., Walsh, M. D., Bates, P., Simmons, D. L., Antalis, T. M.
|
|
<strong>The deleted in colon cancer (DCC) gene is consistently expressed in colorectal cancers and metastases.</strong>
|
|
Oncogene 13: 787-795, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8761300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8761300</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8761300" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Hohne1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hohne, M. W., Halatsch, M.-E., Kahl, G. F., Weinel, R. J.
|
|
<strong>Frequent loss of expression of the potential tumor suppressor gene DCC in ductal pancreatic adenocarcinoma.</strong>
|
|
Cancer Res. 52: 2616-2619, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1314700/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1314700</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1314700" 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="14" class="mim-anchor"></a>
|
|
<a id="Jamuar2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jamuar, S. S., Schmitz-Abe, K., D'Gama, A. M., Drottar, M., Chan, W.-M., Peeva, M., Servattalab, S., Lam, A.-T. N., Delgado, M. R., Clegg, N. J., Al Zayed, Z., Dogar, M. A., and 14 others.
|
|
<strong>Biallelic mutations in human DCC cause developmental split-brain syndrome.</strong>
|
|
Nature Genet. 49: 606-612, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28250456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28250456</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28250456[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=28250456" target="_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/ng.3804" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Jen1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jen, J., Kim, H., Piantadosi, S., Liu, Z.-F., Levitt, R. C., Sistonen, P., Kinzler, K. W., Vogelstein, B., Hamilton, S. R.
|
|
<strong>Allelic loss of chromosome 18q and prognosis in colorectal cancer.</strong>
|
|
New Eng. J. Med. 331: 213-221, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8015568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8015568</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8015568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM199407283310401" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Justice1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Justice, M. J., Gilbert, D. J., Kinzler, K. W., Vogelstein, B., Buchberg, A. M., Ceci, J. D., Matsuda, Y., Chapman, V. M., Patriotis, C., Makris, A., Tsichlis, P. N., Jenkins, N. A., Copeland, N. G.
|
|
<strong>A molecular genetic linkage map of mouse chromosome 18 reveals extensive linkage conservation with human chromosomes 5 and 18.</strong>
|
|
Genomics 13: 1281-1288, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1354644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1354644</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1354644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(92)90047-v" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Keino-Masu1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Keino-Masu, K., Masu, M., Hinck, L., Leonardo, E. D., Chan, S. S.-Y., Culotti, J. G., Tessier-Lavigne, M.
|
|
<strong>Deleted in colorectal cancer (DCC) encodes a netrin receptor.</strong>
|
|
Cell 87: 175-185, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8861902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8861902</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8861902" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0092-8674(00)81336-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Keynes1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Keynes, R., Cook, G. M. W.
|
|
<strong>Axon guidance molecules.</strong>
|
|
Cell 83: 161-169, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585933/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585933</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7585933" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(95)90157-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Kolodziej1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kolodziej, P. A., Timpe, L. C., Mitchell, K. J., Fried, S. R., Goodman, C. S., Jan, L. Y., Jan, Y. N.
|
|
<strong>Frazzled encodes a Drosophila member of the DCC immunoglobulin subfamily and is required for CNS and motor axon guidance.</strong>
|
|
Cell 87: 197-204, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8861904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8861904</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8861904" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0092-8674(00)81338-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Krimpenfort2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Krimpenfort, P., Song, J.-Y., Proost, N., Zevenhoven, J., Jonkers, J., Berns, A.
|
|
<strong>Deleted in colorectal carcinoma suppresses metastasis in p53-deficient mammary tumours.</strong>
|
|
Nature 482: 538-541, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22358843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22358843</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22358843" target="_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/nature10790" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Li2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, W., Lee, J., Vikis, H. G., Lee, S.-H., Liu, G., Aurandt, J., Shen, T.-L., Fearon, E. R., Guan, J.-L., Han, M., Rao, Y., Hong, K., Guan, K.-L.
|
|
<strong>Activation of FAK and Src are receptor-proximal events required for netrin signaling.</strong>
|
|
Nature Neurosci. 7: 1213-1221, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15494734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15494734</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15494734[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=15494734" target="_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/nn1329" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Liu2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Liu, G., Beggs, H., Jurgensen, C., Park, H.-T., Tang, H., Gorski, J., Jones, K. R., Reichardt, L. F., Wu, J., Rao, Y.
|
|
<strong>Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth and attraction.</strong>
|
|
Nature Neurosci. 7: 1222-1232, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15494732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15494732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15494732[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=15494732" target="_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/nn1331" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Lynch1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lynch, H. T., Schuelke, G. S., Kimberling, W. J., Albano, W. A., Lynch, J. F., Biscone, K. A., Lipkin, M. L., Deschner, E. E., Mikol, Y. B., Sandberg, A. A., Elston, R. C., Bailey-Wilson, J. E., Danes, B. S.
|
|
<strong>Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). II. Biomarker studies.</strong>
|
|
Cancer 56: 939-951, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4016686/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4016686</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4016686" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/1097-0142(19850815)56:4<939::aid-cncr2820560440>3.0.co;2-t" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Maesawa1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maesawa, C., Tamura, G., Ogasawara, S., Suzuki, Y., Sakata, K., Sugimura, J., Nishizuka, S., Sato, N., Ishida, K., Saito, K., Satodate, R.
|
|
<strong>Loss of heterozygosity at the DCC gene locus is not crucial for the acquisition of metastatic potential in oesophageal squamous cell carcinoma.</strong>
|
|
Europ. J. Cancer. 32A: 896-898, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9081374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9081374</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9081374" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0959-8049(96)00010-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Marsh2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Marsh, A. P. L., Heron, D., Edwards, T. J., Quartier, A., Galea, C., Nava, C., Rastetter, A., Moutard, M.-L., Anderson, V., Bitoun, P., Bunt, J., Faudet, A., and 41 others.
|
|
<strong>Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance.</strong>
|
|
Nature Genet. 49: 511-514, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28250454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28250454</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28250454" target="_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/ng.3794" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Mazelin2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mazelin, L., Bernet, A., Bonod-Bidaud, C., Pays, L., Arnaud, S., Gespach, C., Bredesen, D. E., Scoazec, J.-Y., Mehlen, P.
|
|
<strong>Netrin-1 controls colorectal tumorigenesis by regulating apoptosis.</strong>
|
|
Nature 431: 80-84, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15343335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15343335</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15343335" target="_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/nature02788" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Mehlen1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mehlen, P., Rabizadeh, S., Snipas, S. J., Assa-Munt, N., Salvesen, G. S., Bredesen, D. E.
|
|
<strong>The DCC gene produce induces apoptosis by a mechanism requiring receptor proteolysis.</strong>
|
|
Nature 395: 801-804, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9796814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9796814</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9796814" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/27441" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Meneret2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meneret, A., Depienne, C., Riant, F., Trouillard, O., Bouteiller, D., Cincotta, M., Bitoun, P., Wickert, J., Lagroua, I., Westenberger, A., Borgheresi, A., Doummar, D., and 18 others.
|
|
<strong>Congenital mirror movements: mutational analysis of RAD51 and DCC in 26 cases.</strong>
|
|
Neurology 82: 1999-2002, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24808016/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24808016</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24808016[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=24808016" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/WNL.0000000000000477" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Miyake1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Miyake, S., Nagai, K., Yoshino, K., Oto, M., Endo, M., Yuasa, Y.
|
|
<strong>Point mutations and allelic deletion of tumor suppressor gene DCC in human esophageal squamous cell carcinomas and their relation to metastasis.</strong>
|
|
Cancer Res. 54: 3007-3010, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8187090/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8187090</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8187090" 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="Nigro1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nigro, J. M., Cho, K. R., Fearon, E. R., Kern, S. E., Ruppert, J. M., Oliner, J. D., Kinzler, K. W., Vogelstein, B.
|
|
<strong>Scrambled exons.</strong>
|
|
Cell 64: 607-613, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1991322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1991322</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1991322" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(91)90244-s" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Nishiyama2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nishiyama, M., Hoshino, A., Tsai, L., Henley, J. R., Goshima, Y., Tessier-Lavigne, M., Poo, M., Hong, K.
|
|
<strong>Cyclic AMP/GMP-dependent modulation of Ca(2+) channels sets the polarity of nerve growth-cone turning.</strong>
|
|
Nature 423: 990-995, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12827203/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12827203</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12827203" target="_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/nature01751" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Ren2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ren, X., Ming, G., Xie, Y., Hong, Y., Sun, D., Zhao, Z., Feng, Z., Wang, Q., Shim, S., Chen, Z., Song, H., Mei, L., Xiong, W.
|
|
<strong>Focal adhesion kinase in netrin-1 signaling.</strong>
|
|
Nature Neurosci. 7: 1204-1212, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15494733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15494733</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15494733" target="_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/nn1330" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Sagi-Dain2020" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sagi-Dain, L., Kurolap, A., Ilivitzki, A., Mory, A., Paperna, T., Regeneron Genetics Center, Kedar, R., Gonzaga-Jauregui, C., Peleg, A., Feldman, H. B.
|
|
<strong>A novel heterozygous loss-of-function DCC netrin 1 receptor variant in prenatal agenesis of corpus callosum and review of the literature.</strong>
|
|
Am. J. Med. Genet. 182A: 205-212, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31697046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31697046</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31697046" target="_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.61404" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Sharafaddinzadeh2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sharafaddinzadeh, N., Bavarsad, R., Yousefkhah, M., Aleali, A. M.
|
|
<strong>Familial mirror movements over five generations. (Letter)</strong>
|
|
Neurology India 56: 482-483, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19127048/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19127048</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19127048" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.4103/0028-3886.44813" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Shi2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shi, M., Guo, C., Dai, J.-X., Ding, Y.-Q.
|
|
<strong>DCC is required for the tangential migration of noradrenergic neurons in locus coeruleus of mouse brain.</strong>
|
|
Molec. Cell. Neurosci. 39: 529-538, 2008. Note: Erratum: Molec. Cell. Neurosci. 45: 84 only, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18771734/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18771734</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18771734" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.mcn.2008.07.023" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Shibata1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shibata, D., Reale, M. A., Lavin, P., Silverman, M., Fearon, E. R., Steele, G., Jr., Jessup, J. M., Loda, M., Summerhayes, I. C.
|
|
<strong>The DCC protein and prognosis in colorectal cancer.</strong>
|
|
New Eng. J. Med. 335: 1727-1732, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8929264/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8929264</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8929264" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM199612053352303" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Srour2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Srour, M., Riviere, J.-B., Pham, J. M. T., Dube, M.-P., Girard, S., Morin, S., Dion, P. A., Asselin, G., Rochefort, D., Hince, P., Diab, S., Sharafaddinzadeh, N., Chouinard, S., Theoret, H., Charron, F., Rouleau, G. A.
|
|
<strong>Mutations in DCC cause congenital mirror movements.</strong>
|
|
Science 328: 592 only, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20431009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20431009</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20431009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1186463" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Stein2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stein, E., Tessier-Lavigne, M.
|
|
<strong>Hierarchical organization of guidance receptors: silencing of netrin attraction by Slit through a Robo/DCC receptor complex.</strong>
|
|
Science 291: 1928-1938, 2001. Note: Expression of Concern: Science 378: 1284 only, 2022.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11239147/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11239147</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11239147" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1058445" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Stein2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stein, E., Zou, Y., Poo, M., Tessier-Lavigne, M.
|
|
<strong>Binding of DCC by netrin-1 to mediate axon guidance independent of adenosine A2B receptor activation.</strong>
|
|
Science 291: 1976-1982, 2001. Note: Expression of Concern: Science 378: 1284 only, 2022.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11239160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11239160</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11239160" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1059391" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Tanaka1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tanaka, K., Oshimura, M., Kikuchi, R., Seki, M., Hayashi, T., Miyaki, M.
|
|
<strong>Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 5 or 18.</strong>
|
|
Nature 349: 340-342, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1670965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1670965</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1670965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/349340a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Tcherkezian2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tcherkezian, J., Brittis, P. A., Thomas, F., Roux, P. P., Flanagan, J. G.
|
|
<strong>Transmembrane receptor DCC associates with protein synthesis machinery and regulates translation.</strong>
|
|
Cell 141: 632-644, 2010. Note: Erratum: Cell 184: 2520 only, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20434207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20434207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20434207[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=20434207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.cell.2010.04.008" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Thiagalingam1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thiagalingam, S., Lengauer, C., Leach, F. S., Schutte, M., Hahn, S. A., Overhauser, J., Willson, J. K. V., Markowitz, S., Hamilton, S. R., Kern, S. E., Kinzler, K. W., Vogelstein, B.
|
|
<strong>Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers.</strong>
|
|
Nature Genet. 13: 343-346, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673134</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8673134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0796-343" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Uchino1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Uchino, S., Tsuda, H., Noguchi, M., Yokota, J., Terada, M., Saito, T., Kobayashi, M., Sugimura, T., Hirohashi, S.
|
|
<strong>Frequent loss of heterozygosity at the DCC locus in gastric cancer.</strong>
|
|
Cancer Res. 52: 3099-3102, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1591722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1591722</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1591722" 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="44" class="mim-anchor"></a>
|
|
<a id="Vogelstein1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vogelstein, B., Fearon, E. R., Hamilton, S. R., Kern, S. E., Preisinger, A. C., Leppert, M., Nakamura, Y., White, R., Smits, A. M. M., Bos, J. L.
|
|
<strong>Genetic alterations during colorectal-tumor development.</strong>
|
|
New Eng. J. Med. 319: 525-532, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2841597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2841597</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2841597" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM198809013190901" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Vogelstein1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vogelstein, B.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 11/30/1995.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Wei2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wei, X., Walia, V., Lin, J. C., Teer, J. K., Prickett, T. D., Gartner, J., Davis, S., NISC Comparative Sequencing Program, Stemke-Hale, K., Davies, M. A., Gershenwald, J. E., Robinson, W., Robinson, S., Rosenberg, S. A., Samuels, Y.
|
|
<strong>Exome sequencing identifies GRIN2A as frequently mutated in melanoma.</strong>
|
|
Nature Genet. 43: 442-446, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21499247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21499247</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21499247[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=21499247" target="_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/ng.810" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Xu2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Xu, K., Wu, Z., Renier, N., Antipenko, A., Tzvetkova-Robev, D., Xu, Y., Minchenko, M., Nardi-Dei, V., Rajashankar, K. R., Himanen, J., Tessier-Lavigne, M., Nikolov, D. B.
|
|
<strong>Structures of netrin-1 bound to two receptors provide insight into its axon guidance mechanism.</strong>
|
|
Science 344: 1275-1279, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24876346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24876346</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24876346[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=24876346" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1255149" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Zetter1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zetter, B. R.
|
|
<strong>Adhesion molecules in tumor metastasis.</strong>
|
|
Semin. Cancer Biol. 4: 219-229, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8400144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8400144</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8400144" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Hilary J. Vernon - updated : 10/22/2021
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 06/28/2017<br>Ada Hamosh - updated : 7/7/2014<br>Ada Hamosh - updated : 3/13/2012<br>Cassandra L. Kniffin - updated : 5/12/2011<br>Cassandra L. Kniffin - updated : 4/14/2011<br>Patricia A. Hartz - updated : 12/14/2010<br>Patricia A. Hartz - updated : 6/3/2010<br>Ada Hamosh - updated : 6/3/2010<br>Ada Hamosh - updated : 10/26/2007<br>Cassandra L. Kniffin - updated : 2/17/2005<br>Ada Hamosh - updated : 11/10/2004<br>Ada Hamosh - updated : 7/8/2003<br>Paul J. Converse - updated : 5/6/2002<br>Ada Hamosh - updated : 3/27/2001<br>Ada Hamosh - updated : 3/27/2001<br>Ada Hamosh - updated : 9/5/2000<br>Victor A. McKusick - updated : 10/22/1998<br>Jennifer P. Macke - updated : 7/11/1997<br>Victor A. McKusick - updated : 6/27/1997<br>Moyra Smith - updated : 7/4/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 2/26/1988
|
|
</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 : 04/15/2024
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 01/21/2023<br>carol : 01/21/2023<br>carol : 11/05/2021<br>carol : 10/22/2021<br>alopez : 01/27/2021<br>carol : 04/02/2019<br>ckniffin : 04/02/2019<br>carol : 04/24/2018<br>carol : 10/27/2017<br>carol : 07/05/2017<br>carol : 07/03/2017<br>carol : 07/03/2017<br>ckniffin : 06/28/2017<br>alopez : 10/07/2016<br>carol : 07/08/2014<br>alopez : 7/7/2014<br>carol : 9/18/2013<br>terry : 9/25/2012<br>alopez : 3/14/2012<br>terry : 3/13/2012<br>carol : 5/13/2011<br>ckniffin : 5/12/2011<br>wwang : 5/3/2011<br>ckniffin : 4/14/2011<br>mgross : 1/4/2011<br>terry : 12/14/2010<br>alopez : 8/31/2010<br>alopez : 6/6/2010<br>terry : 6/3/2010<br>terry : 6/3/2010<br>ckniffin : 2/5/2008<br>ckniffin : 1/16/2008<br>alopez : 11/1/2007<br>terry : 10/26/2007<br>alopez : 7/5/2007<br>wwang : 2/17/2005<br>tkritzer : 11/10/2004<br>mgross : 7/14/2003<br>mgross : 7/14/2003<br>terry : 7/8/2003<br>tkritzer : 6/19/2003<br>alopez : 6/7/2002<br>mgross : 5/6/2002<br>alopez : 3/27/2001<br>alopez : 3/27/2001<br>alopez : 9/5/2000<br>alopez : 10/22/1998<br>terry : 10/22/1998<br>carol : 7/30/1998<br>jenny : 9/2/1997<br>jenny : 8/14/1997<br>jenny : 7/2/1997<br>terry : 6/27/1997<br>mark : 1/6/1997<br>terry : 1/3/1997<br>mark : 12/20/1996<br>mark : 12/20/1996<br>terry : 12/10/1996<br>terry : 12/9/1996<br>terry : 9/17/1996<br>marlene : 8/15/1996<br>mark : 7/5/1996<br>mark : 7/4/1996<br>mark : 12/18/1995<br>mark : 12/15/1995<br>terry : 12/6/1995<br>carol : 11/18/1994<br>terry : 8/25/1994<br>carol : 12/22/1993<br>carol : 12/17/1993<br>carol : 3/29/1993<br>carol : 11/3/1992
|
|
</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> 120470
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
DCC NETRIN 1 RECEPTOR; DCC
|
|
|
|
</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">
|
|
NETRIN RECEPTOR DCC<br />
|
|
DELETED IN COLORECTAL CARCINOMA<br />
|
|
COLORECTAL CANCER-RELATED CHROMOSOME SEQUENCE 18; CRC18<br />
|
|
CRCR1
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: DCC</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 18q21.2
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 18:52,340,197-53,535,899 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="4">
|
|
<span class="mim-font">
|
|
18q21.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Colorectal cancer, somatic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
114500
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Esophageal carcinoma, somatic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
133239
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Gaze palsy, familial horizontal, with progressive scoliosis, 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
617542
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Mirror movements 1 and/or agenesis of the corpus callosum
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
157600
|
|
</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 DCC gene encodes a functional receptor for netrin (NTN1; 601614) and mediates axon outgrowth and the steering response (summary by Li et al., 2004). </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>Vogelstein et al. (1988) found that chromosome 18 sequences were lost frequently in colorectal carcinomas (73%) and in advanced adenomas (47%), but only occasionally in earlier-stage adenomas (11 to 13%). Taken in connection with other findings of changes in chromosome 17, as well as chromosome 5, these findings suggested a model wherein the steps required for malignancy often involve the activation of a dominantly acting oncogene coupled with the loss of several genes that normally suppress tumorigenesis. The critical area in chromosome 18 appeared to reside between 18q21.3 and the telomere. </p><p>Fearon et al. (1990) cloned a contiguous stretch of DNA, comprising 370 kb, from the region of 18q suspected to contain the tumor suppressor gene. Potential exons in the 370-kb region were defined by human-rodent sequence identities, and the expression of potential exons was assessed by an 'exon-connection' strategy based on the polymerase chain reaction. Expressed exons were used as probes for screening of cDNA to obtain clones that encoded a gene the authors termed DCC ('deleted in colorectal carcinomas'). This cDNA was encoded by at least 8 exons. The predicted amino acid sequence specified a protein with sequence similarity to neural cell adhesion molecules (116930) and related cell surface glycoproteins. While the DCC gene was expressed in most normal tissues, including colonic mucosa, its expression was greatly reduced or absent in most colorectal carcinomas tested. Somatic mutations within the DCC gene observed in colorectal cancers included a homozygous deletion of the 5-prime end, a point mutation within one of the introns, and 10 examples of DNA insertions within a 0.17-kb fragment immediately downstream of 1 of the exons. </p><p>In the embryonic mouse brain, Jamuar et al. (2017) found expression of the Dcc gene in the telencephalic cortical plate as well as in the developing brainstem nuclei. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Cho et al. (1994) commented that the DCC gene encodes a protein with sequence similarity to cell adhesion molecules such as N-CAM (116930). Studying a YAC contig containing the entire DCC coding region, they showed that the DCC gene spans approximately 1.4 Mb. They used lambda phage clones to demonstrate the existence of 29 DCC exons, and the sequences of the exon-intron boundaries were determined. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
Xu et al. (2014) determined the structures of a functional NTN1 (601614) region, alone and in complexes with NEO1 (601907) and DCC. NTN1 has a rigid elongated structure containing 2 receptor-binding sites at opposite ends through which it brings together receptor molecules. The ligand/receptor complexes reveal 2 distinct architectures: a 2:2 heterotetramer and a continuous ligand/receptor assembly. The differences result from different lengths of the linker connecting receptor domains fibronectin type III domain 4 (FN4) and FN5, which differs among DCC and NEO1 splice variants, providing a basis for diverse signaling outcomes. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using molecular markers in an interspecific backcross between C57BL/6J and Mus spretus, Justice et al. (1992) mapped the corresponding gene to mouse chromosome 18. </p><p>Vogelstein (1995) stated that the precise location of the DCC gene was thought to be 18q21.3.</p><p>Thiagalingam et al. (1996) evaluated sporadic colon cancer tumors for allelic deletions. They defined a minimally lost region (MLR) on chromosome 18q21 which extended between markers D18S535 and D18S858. It encompassed 16 cM between D18S535 and 20CO3 and included 2 candidate tumor suppressor genes: DPC4 (600993) and DCC. DPC4 was deleted in up to one-third of cases and DCC or a neighboring gene was deleted in the remaining tumors. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Keino-Masu et al. (1996) noted that the establishment of neuronal connections involves the accurate guidance of developing axons to their targets through the combined actions of attractive and repulsive guidance cues in the extracellular environment. Diffusible chemoattractants secreted by target cells are involved, as well as diffusible chemorepellents secreted by nontarget cells which generate exclusion zones that axons avoid (Keynes and Cook, 1995). Two families of guidance molecules, the netrins (see netrin-1, 601614) and semaphorins (see 601281 and 601124), are proteins that can function as diffusible attractants or repellents for developing neurons, but the receptors and signal transduction mechanisms through which they produce their effects are poorly understood. Netrins are chemoattractants for commissural axons in the vertebral spinal cord. Keino-Masu et al. (1996) showed that DCC, a transmembrane protein of the immunoglobulin superfamily, is expressed on spinal commissural axons and possesses netrin-1-binding activity. Moreover, an antibody to DCC selectively blocked the netrin-1-dependent outgrowth of commissural axons in vitro. These results indicated that DCC is a receptor or a component of a receptor that mediates the effects of netrin-1 on commissural axons, and they complement genetic evidence for interactions between DCC and netrin homologs in C. elegans (UNC40; see Chan et al., 1996) and Drosophila (frazzled; see Kolodziej et al., 1996). </p><p>Using RT-PCR, Gotley et al. (1996) detected DCC mRNA in all colonic tissue specimens through all stages of tumor development. Using monoclonal antibodies against DCC, they found DCC protein is abundant in normal human bladder and is detectable in colon, pancreas and kidney, but not in liver. DCC protein could be detected in varying abundance in all specimens of normal colonic mucosa analyzed as well as in all specimens of adenomatous polyps, colorectal carcinoma and colorectal liver metastases. In some patients, tumor tissue contained less DCC protein than the adjacent normal mucosa. Gotley et al. (1996) found no cases of complete loss of DCC mRNA or protein in colon cancers or metastases. </p><p>Mehlen et al. (1998) showed that DCC induces apoptosis in the absence of ligand binding, but blocks apoptosis when engaged by netrin-1. Furthermore, DCC is a caspase substrate, and mutation of the site at which caspase-3 (CASP3; 600636) cleaves DCC suppresses the proapoptotic effect of DCC completely. These results indicated the DCC may function as a tumor-suppressor protein by inducing apoptosis in settings in which ligand is unavailable (for example, during metastasis or tumor growth beyond local blood supply) through functional caspase cascades by a mechanism that requires cleavage of DCC at asp1290. </p><p>The axonal chemoattractant netrin-1 guides spinal commissural axons by activating its receptor DCC. Galko and Tessier-Lavigne (2000) found that chemical inhibitors of metalloproteases potentiate netrin-mediated axon outgrowth in vitro. Galko and Tessier-Lavigne (2000) also found that DCC is a substrate for metalloprotease-dependent ectodomain shedding, and that the inhibitors block proteolytic processing of DCC and cause an increase in DCC protein levels on axons within spinal cord explants. Thus, Galko and Tessier-Lavigne (2000) suggested that potentiation of netrin activity by inhibitors may result from stabilization of DCC on the axons, and proteolytic activity may regulate axon migration by controlling the number of functional extracellular axon guidance receptors. </p><p>Stein et al. (2001) demonstrated that netrin-1 binds DCC and that the DCC cytoplasmic domain fused to a heterologous receptor ectodomain can mediate guidance through a mechanism involving derepression of cytoplasmic domain multimerization. Activation of the adenosine A2B receptor (600446), proposed to contribute to netrin effects on axons, is not required for rat commissural axon outgrowth or Xenopus spinal axon attraction to netrin-1. Thus, Stein et al. (2001) concluded that DCC plays a central role in netrin signaling of axon growth and guidance independent of A2B receptor activation. Note that an expression of concern has been published for the article by Stein et al. (2001). </p><p>Axonal growth cones that cross the nervous system midline change their responsiveness to midline guidance cues: they become repelled by the repellent Slit (603746) and simultaneously lose responsiveness to the attractant netrin. These mutually reinforcing changes help to expel growth cones from the midline by making a once-attractive environment appear repulsive. Stein and Tessier-Lavigne (2001) provided evidence that these 2 changes are causally linked: in the growth cones of embryonic Xenopus spinal axons, activation of the Slit receptor Roundabout (Robo; 602430) silences the attractive effect of netrin-1, but not its growth-stimulatory effect, through direct binding of the cytoplasmic domain of Robo to that of the netrin receptor DCC. Biologically, this hierarchical silencing mechanism helps to prevent a tug-of-war between attractive and repulsive signals in the growth cone that might cause confusion. Molecularly, silencing is enabled by a modular and interlocking design of the cytoplasmic domains of these potentially antagonistic receptors that predetermines the outcome of their simultaneous activation. Note that an expression of concern was published for the article by Stein and Tessier-Lavigne (2001). </p><p>Forcet et al. (2002) showed that in embryonic kidney cells expressing full-length, but not cytoplasmic domain-truncated, DCC, NTN1 causes increased transient phosphorylation and activity of ERK1 (601795) and ERK2 (176948), but not of JNK1 (601158), JNK2 (602896), or p38 (MAPK14; 600289). This phosphorylation was mediated by MEK1 (MAP2K1; 176872) and/or MEK2 (MAP2K2; 601263). NTN1 also activated the transcription factor ELK1 (311040) and serum response element-regulated gene expression. Immunoprecipitation analysis showed interaction of full-length DCC with MEK1/2 in the presence or absence of NTN1. Forcet et al. (2002) showed that activation of Dcc by Ntn1 in rat embryonic day-13 dorsal spinal cord stimulates and is required for the outgrowth of commissural axons and Erk1/2 activation. Immunohistochemical analysis demonstrated expression of activated Erk1/2 in embryonic commissural axons, and this expression was diminished in Dcc or Ntn1 knockout animals. Forcet et al. (2002) concluded that the MAPK pathway is involved in responses to NTN1 and proposed that ERK activation affects axonal growth by phosphorylation of microtubule-associated proteins and neurofilaments. </p><p>Nishiyama et al. (2003) reported that the ratio of cyclic AMP to cyclic GMP activities sets the polarity of netrin-1-induced axon guidance: high ratios favor attraction, whereas low ratios favor repulsion. Whole-cell recordings of calcium currents in Xenopus spinal neuron growth cones indicated that cyclic nucleotide signaling directly modulates the activity of L-type calcium channels in axonal growth cones. Furthermore, cyclic GMP signaling activated by an arachidonate 12-lipoxygenase metabolite suppressed L-type calcium channel activity triggered by netrin-1 and was required for growth cone repulsion mediated by the DCC-UNC5 (see 603610) receptor complex. By linking cyclic AMP and cyclic GMP signaling and modulation of calcium channel activity in growth cones, these findings delineated an early membrane-associated event responsible for signal transduction during bidirectional axon guidance. </p><p>Mehlen et al. (1998) showed that DCC induces apoptosis conditionally: by functioning as a dependence receptor, DCC induces apoptosis unless it is engaged by its ligand netrin-1. Mazelin et al. (2004) demonstrated that inhibition of cell death by enforced expression of netrin-1 in mouse gastrointestinal tract led to the spontaneous formation of hyperplastic and neoplastic lesions. Moreover, in the adenomatous polyposis coli mutant background associated with adenoma formation, enforced expression of netrin-1 engendered aggressive adenocarcinomatous malignancies. Mazelin et al. (2004) concluded that netrin-1 can promote intestinal tumor development, probably by regulating cell survival. Thus, a netrin-1 receptor or receptors function as conditional tumor suppressors. </p><p>Netrin proteins play a role in the developing nervous system by promoting both axonal outgrowth and axonal guidance in pathfinding. Liu et al. (2004), Li et al. (2004), and Ren et al. (2004) simultaneously reported a complex network of intracellular signaling downstream from netrin-1 (601614) involving DCC, focal adhesion kinase (FAK; 600758), and FYN (137025), a member of the SRC family kinases (see 190090). In neurons cultured from rat cerebral cortex, Liu et al. (2004) found that netrin-1 induced tyrosine phosphorylation of FAK and FYN, and coimmunoprecipitation studies showed direct interaction of FAK and FYN with DCC. Inhibition of FYN inhibited FAK phosphorylation, and FYN mutants inhibited the attractive turning responses to netrin. Neurons lacking the FAK gene showed reduced axonal outgrowth and attractive turning responses to netrin. In cultured neurons from chick and mouse, Li et al. (2004) found that netrin increased tyrosine phosphorylation of DCC and FAK. Coimmunoprecipitation studies showed that DCC interacted directly with FAK and SRC to form a complex and that FAK and SRC cooperated to stimulate DCC phosphorylation by SRC. Li et al. (2004) suggested that phosphorylated DCC acts as a kinase-coupled receptor and that FAK and SRC act downstream of DCC in netrin signaling. Ren et al. (2004) found that inhibition of FAK phosphorylation inhibited netrin-1-induced axonal outgrowth and guidance. The authors suggested that FAK may also function as a scaffolding protein and play a role in cytoskeletal reorganization that is necessary for neurite outgrowth and turning. </p><p>Colon-Ramos et al. (2007) showed that connectivity between 2 interneurons in C. elegans, AIY and RIA, is orchestrated by a pair of glial cells that express UNC6 (netrin-1). In the postsynaptic neuron RIA, the netrin receptor UNC40 (DCC) plays a conventional guidance role directing outgrowth of the RIA process ventrally toward the glia. The authors determined that in the presynaptic neuron AIY, UNC40 plays an unexpected and theretofore uncharacterized role: it cell-autonomously promotes assembly of presynaptic terminals in the immediate vicinity of the glial cell endfeet. Colon-Ramos et al. (2007) concluded that netrin can be used both for guidance and local synaptogenesis and suggested that glial cells can function as guideposts during the assembly of neural circuits in vivo. </p><p>Tcherkezian et al. (2010) found that Ddc partly colocalized with the translational machinery in embryonic mouse spinal commissural axon growth cones and in rat hippocampal neuron dendrites. Ddc coprecipitated with components of translation machinery in transfected 293 cells, and this coprecipitation required the Ddc intracellular domain. Ddc associated particularly with translation initiation components. Mutation analysis and mass spectrometry revealed that the P1 motif of the Ddc intracellular domain interacted specifically and directly with ribosomal protein L5 (RPL5; 603634). Labeling studies revealed that Ddc overlapped with newly synthesized proteins at the tips of commissural neuron filopodia and in hippocampal neurons. Netrin-1 promoted translation in a Ddc-dependent manner and reduced association of Ddc with translation components. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Congenital Mirror Movements 1 and/or Agenesis of the Corpus Callosum</em></strong></p><p>
|
|
Srour et al. (2010) identified 2 frameshift mutations in the DCC gene in 2 families with congenital mirror movements (MRMV1; 157600). In a large French Canadian family, they identified a splice site mutation in intron 6 leading to a frameshift and exon skipping (120470.0003), and in an Iranian family they identified a single-nucleotide insertion in exon 3 (120470.0004). Srour et al. (2010) proposed that DCC mutations in individuals with congenital mirror movements cause a reduction in gene dosage and less robust midline guidance, which may lead to a partial failure of axonal fiber crossing and development of abnormal ipsilateral connection. </p><p>In individuals from 4 unrelated multigenerational families with congenital mirror movements and/or agenesis of the corpus callosum, Marsh et al. (2017) identified heterozygous mutations in the DCC gene (120470.0006-120470.0009). The mutations were found by a combination of methods, including linkage analysis, whole-exome sequencing, and direct sequencing. Two mutations were truncating mutations, predicted to result in haploinsufficiency, and 2 were missense mutations affecting the netrin-1 binding domain. Heterozygous missense DCC mutations were subsequently found in 5 of 70 probands with isolated ACC. Functional studies of the variants and studies of patient cells were not performed. In a review of individuals with mutations in the DCC gene in their study and in the literature, Marsh et al. (2017) found significant incomplete penetrance: the penetrance of mirror movements was estimated to be 42%, and the penetrance of ACC was estimated to be 26%. There was some evidence for a male bias in phenotypic manifestations, and in vitro studies suggested that androgens could influence DCC expression. Marsh et al. (2017) concluded that there are additional genetic, epigenetic, and environmental factors that influence the expression of the disorder, including developmental differences between the corpus callosum and corticospinal tract. Corticospinal axons and callosal axons use slightly different signaling to approach and cross midline, such that a DCC mutation may differentially affect commissural versus subcerebral axon trajectories, resulting in the variable features of mirror movements, ACC, or both. Mirror movements were consistently associated with decreased crossing of descending corticospinal tract projections at the pyramidal decussation; ACC was associated with absence of the hippocampal commissure and cingulate gyri, as well as and dysmorphic lateral ventricles. The individuals had normal to borderline intellectual disability and a more favorable outcome compared to the developmental outcomes associated with syndromic forms of ACC. Marsh et al. (2017) concluded that prenatal detection of isolated ACC related to a pathogenic DCC mutation is indicative of a lower risk of a poor neurodevelopmental outcome. </p><p>In 5 members of an Ethiopian Jewish family with MRMV1, Sagi-Dain et al. (2020) identified heterozygosity for a frameshift mutation in the DCC gene (120470.0012). The mutation, which was found by whole-exome sequencing, was also identified in an asymptomatic female family member. A fetus with agenesis of the corpus callosum from a terminated pregnancy in this family was not tested for the mutation. </p><p><strong><em>Familial Horizontal Gaze Palsy with Progressive Scoliosis 2 with Impaired Intellectual Development</em></strong></p><p>
|
|
In 3 patients from 2 unrelated families with familial horizontal gaze palsy with progressive scoliosis-2 with impaired intellectual development (HGPPS2; 617542), Jamuar et al. (2017) identified homozygous intragenic deletions in the DCC gene (120470.0010-120470.0011), both resulting in premature termination and functional null alleles. The deletion in the first family was found by a combination of homozygosity mapping and CNV analysis; the deletion in the second family was found by targeted sequencing of the DCC gene. The patients had agenesis of the corpus callosum, absence of the anterior and hippocampal commissures, hypoplasia of the pons and midbrain, and midline cleft throughout the brainstem, contributing to a butterfly-shaped medulla. The findings confirmed that DCC is essential for both forebrain and brainstem midline crossing in the human central nervous system. An unrelated patient with ACC and mild intellectual disability was found to have a homozygous missense variant in the DCC gene (Q691K) at a conserved residue in the third fibronectin repeat, but no clinical information was available and functional studies of the variant were not performed. </p><p><strong><em>Loss of Heterozygosity in Tumors</em></strong></p><p>
|
|
In a study of 28 cases of surgically resected gastric cancer, excluding the diffuse type, Uchino et al. (1992) concluded that loss of heterozygosity (LOH) on chromosome 18q occurs at an earlier stage than LOH on chromosome 17p and that tumor suppressor genes located on these 2 chromosome arms are critically involved in the development of most gastric cancers. Involvement of DCC may be rather selective for gastrointestinal cancers. </p><p>Hohne et al. (1992) presented evidence that loss of DCC gene expression is an important factor in the development or progress of pancreatic adenocarcinoma. In 8 of 11 pancreatic carcinoma cell lines and in 4 of 8 primary ductal adenocarcinomas of the pancreas, a complete extinction of DCC gene expression was observed, whereas the KRAS gene (190070) was mutated at codon 12 in 7 of the 8 primary tumors. Reduced or absent DCC expression tended to be associated with undifferentiated pancreatic tumor cell lines, whereas in the more differentiated ones, DCC expression was conserved. </p><p>In a panel of primary colorectal tumors, Cho et al. (1994) found that most had lost the region containing DCC. </p><p>The DCC protein has structural features in common with certain types of cell-adhesion molecules and may participate with other proteins in cell-cell and cell-matrix interactions. Zetter (1993) found that expression of the DCC gene was absent in most colorectal cancers that were metastatic to the liver, but was lost only in a minority of nonmetastatic cancers. Furthermore, Jen et al. (1994) found that allelic loss of 18q in the region occupied by the DCC gene carried a worse prognosis than that in cases with no loss of chromosome 18q. They developed procedures to examine the status of 18q with microsatellite markers and PCR-amplified DNA from formalin-fixed, paraffin-embedded tumors. Normal tissue and tumor tissue could be examined on the same microscopic slide. Allelic loss of 18q was assessed in 145 consecutively resected stage II or III colorectal carcinomas. The prognosis in patients with stage II cancer (Dukes stage B; tumor extending through the bowel wall, without lymph-node metastasis) was similar to that in patients with stage III cancer, who were thought to benefit from adjuvant therapy. In contrast, patients with stage II disease who did not have chromosome 18q allelic loss in their tumor had a survival rate similar to that of patients with stage I disease and might not require additional therapy. </p><p>Shibata et al. (1996) reported findings that extended the observations of Jen et al. (1994), who had found that allelic loss of 18q predicted a poor outcome in patients with stage II colorectal cancer. They studied the DCC gene as a possible specific prognostic marker. Expression of DCC was evaluated immunohistochemically in 132 paraffin-embedded samples from patients with curatively resected stage II or stage III colorectal carcinomas. They found that expression of DCC was a strong positive predictive factor for survival in both stage II and stage III colorectal carcinomas. In patients with stage II disease whose tumors expressed DCC, the 5-year survival rate was 94.3%, whereas in patients with DCC-negative tumors, the survival rate was 61.6%. In patients with stage III disease, the respective survival rates were 59.3% and 33.2%. </p><p>Maesawa et al. (1996) screened tumor specimens from 111 patients with esophageal squamous cell carcinoma for LOH at the DCC locus and observed LOH in 10 of 61 informative cases (16%). No statistically significant correlation was observed between DCC-LOH and lymph node metastasis, histopathologic grade, or tumor stage. Survivorship of DCC-LOH patients was not statistically different from that of patients without LOH. These results suggested to Maesawa et al. (1996) that LOH at the DCC locus is not related to the acquisition of metastatic potential or the state of tumor cell differentiation in esophageal squamous cell carcinoma. </p><p><strong><em>Somatic Mutations</em></strong></p><p>
|
|
Cho et al. (1994) found a somatic missense mutation in a colorectal tumor (120470.0001). </p><p>Miyake et al. (1994) identified somatic missense mutations and loss of heterozygosity in esophageal tumors (see 120470.0002). </p><p>Using exome sequencing, Wei et al. (2011) identified a recurrent somatic gly55-to-glu (G55E) mutation in the DCC gene in 3 (2%) of 167 melanoma (see 155600) samples. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
For discussion of a possible association between variation in the DCC gene and hypogonadotropic hypogonadism, see 147950.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Finger et al. (2002) described a spontaneous mutation in mice, 'kanga,' that resulted in mild to severe inability to maintain an upright position. Mutant mice often moved their hind legs in a concerted manner, resulting in a somewhat hopping gait. Finger et al. (2002) found that the kanga phenotype results from deletion of exon 29 of the Dcc gene. Immunohistochemical analysis revealed that the corticospinal tract of kanga/kanga mice showed abnormalities at the pyramidal decussation. While homozygous mutation of the Dcc gene disrupted the decussation of all corticospinal tract axons, in Unc5h3 (603610)-mutant mice corticospinal tract fibers that crossed the midline were found in the contralateral lateral funiculus but not the ventral funiculus. Finger et al. (2002) also found that Unc5h3 and Dcc act synergistically in guiding corticospinal tract axons. </p><p>To help elucidate the functions of the DCC gene and to test the suggestion that it functions as a receptor for the axonal chemoattractant netrin-1, Fazeli et al. (1997) inactivated the DCC homolog in the mouse genome through use of homologous recombination and studied the effects of this inactivation on both the intestine and the developing nervous system. They found defects in axonal projections that were similar to those observed in netrin-1-deficient mice, but there was no effect on growth, differentiation, morphogenesis, or tumorigenesis in mouse intestine. These observations failed to support a tumor-suppressor function for DCC in the mouse, but were consistent with the hypothesis that DCC is a component of the receptor for netrin-1. </p><p>Using wildtype and Dcc -/- mouse embryos, Shi et al. (2008) found that Dcc was expressed in neurons of the locus ceruleus and that Dcc was required for normal locus ceruleus development. Locus ceruleus-specific gene expression was normal in Dcc-null embryos, but the initiation of tangential migration of locus ceruleus neurons was delayed. Subsequently, locus ceruleus neurons in Dcc-null mice were misdirected to the pons or ectopically located in the cerebellum. Migration of locus ceruleus neurons and the morphology of the locus ceruleus was not compromised in kanga/kanga mice, demonstrating that the C-terminal domain required for commissural axon guidance is not necessary for the proper development of the locus ceruleus. </p><p>To investigate the role of DCC-induced apoptosis in the control of tumor progression, Castets et al. (2011) created a mouse model in which the proapoptotic activity of DCC is genetically silenced. Although the loss of DCC-induced apoptosis in this mouse model was not associated with a major disorganization of the intestines, it led to spontaneous intestinal neoplasia at a relatively low frequency. Loss of DCC-induced apoptosis was also associated with an increase in the number and aggressiveness of intestinal tumors in a predisposing APC (611731) mutant context, resulting in the development of highly invasive adenocarcinomas. Castets et al. (2011) concluded that DCC functions as a tumor suppressor via its ability to trigger tumor cell apoptosis. </p><p>Krimpenfort et al. (2012) showed that in a mouse model of mammary carcinoma based on somatic inactivation of p53 (191170), additional loss of DCC promotes metastasis formation without affecting the primary tumor phenotype. Furthermore, they demonstrated that in cell cultures derived from p53-deficient mouse mammary tumors, DCC expression controls netrin-1 (601614)-dependent cell survival, providing a mechanistic basis for the enhanced metastatic capacity of tumor cells lacking DCC. Consistent with this idea, in vivo tumor cell survival is enhanced by DCC loss. Krimpenfort et al. (2012) concluded that their data supported the function of DCC as a context-dependent tumor suppressor that limits survival of disseminated tumor cells. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>It is of interest that Lynch et al. (1985) found a lod score of 3.19 for linkage between a familial cancer syndrome (Lynch syndrome II; 120435) and Kidd blood group (JK; 111000); the Kidd blood group has been assigned to 18q11-q12. </p><p>Bowman et al. (1988) found tumor-specific allele loss at the D18S6 locus on chromosome 18 in 2 patients with familial adenomatous polyposis and in 2 patients with sporadic colon cancer. D18S6 is closely linked to LCFS2 and JK. </p><p>Tanaka et al. (1991) demonstrated that transfer of a normal human chromosome 18 into a colon carcinoma cell line through microcell hybridization severely reduced the cloning efficiency of the hybrid cells in soft agar and completely suppressed tumorigenicity in athymic nude mice. Similar results were obtained when a normal chromosome 5, which carries the locus for adenomatous polyposis coli (611731), was transferred into the cells, but the growth properties of the hybrid cells were unchanged when chromosome 11 was introduced. </p><p>Nigro et al. (1991) observed a curious phenomenon of scrambled exons in the DCC gene in a variety of normal and neoplastic cells of rodent and human origin. Abnormally spliced transcripts showed that exons were joined accurately at consensus splice sites, but in an order different from that present in the primary transcript. Thus, a novel type of RNA product resulted. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>12 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 COLORECTAL CANCER, SOMATIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCC, PRO-HIS, 4124C-A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906555,
|
|
|
|
|
|
gnomAD: rs387906555,
|
|
|
|
|
|
ClinVar: RCV000018603
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>To look for structural alterations of the DCC gene, Cho et al. (1994) analyzed 60 colorectal cancers matched with normal DNA samples from the same individual, using Southern blot hybridization to DCC cDNA probes. In 1 tumor, an altered pattern of EcoRI fragments was found and shown to have its basis in a somatically acquired point mutation in intron 13. The sequences flanking the mutation had features suggestive of an exon, including a short open reading frame and consensus splice acceptor and donor sites. These findings suggested that the tumor contained a mutation in an alternatively utilized exon. To search for more subtle alterations, Cho et al. (1994) evaluated several exons and their flanking intron sequences for the presence of mutations in 30 colorectal cancers by an RNase protection assay. A C-to-A transversion at position 4124 in exon 28 was identified in 1 tumor. This mutation was predicted to result in a nonconservative amino acid change from proline to histidine. It was absent from the DNA of normal lymphocytes from the same patient. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 ESOPHAGEAL CARCINOMA, SOMATIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCC, MET168THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912967,
|
|
|
|
|
|
|
|
ClinVar: RCV000018604
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Since the tumor suppressor gene DCC shows amino acid sequence homology to the neural cell adhesion molecule (116930), Miyake et al. (1994) considered the possibility that DCC might be related to tumor metastasis. They examined 51 cases of primary esophageal carcinoma for point mutations and loss of the gene. By screening using PCR-single strand conformation polymorphism analysis, they found point mutations in 2 cases. One case with lymph node metastasis showed an ATG-(met)-to-ACC-(thr) missense mutation in codon 168. Another case showed a CGA (arg)-to-GGA (gly) mutation in codon 201, which might be a polymorphic change, and 2 other mutations resulting in no amino acid change. Forty-four of the 51 cases (86%) were informative for loss of heterozygosity of the DCC gene; of these, 10 (23%) showed allelic deletion. The further away the lymph node metastasis was from the primary tumor, the higher the frequency of allelic deletions. They also found allelic deletions in moderately and poorly differentiated squamous cell carcinomas but not in well-differentiated ones. They interpreted these findings to indicate that alterations in the DCC gene are related to the degree of lymph node metastasis and the degree of differentiation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 MIRROR MOVEMENTS 1 AND/OR AGENESIS OF THE CORPUS CALLOSUM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCC, IVS6DS, G-A, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs797044553,
|
|
|
|
|
|
|
|
ClinVar: RCV000192080, RCV003441766
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a large 4-generation French Canadian family segregating autosomal dominant congenital mirror movements (MRMV1; 157600) with incomplete penetrance, Srour et al. (2010) identified a G-to-A transition at nucleotide 1140 of the DCC gene, at the splice donor site of intron 6 (1140+1G-A). This mutation led to skipping of exon 6 and a frameshift after amino acid 329 with the introduction of a stop codon 15 amino acids further down the new reading frame (Val329GlyfsTer15). This mutation segregated with the risk haplotype and was not found in 760 unrelated Caucasian controls, including 512 French Canadians. Copy number variation analysis in 315 French Canadian controls did not reveal any structural variations encompassing DCC exons. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 MIRROR MOVEMENTS 1 AND/OR AGENESIS OF THE CORPUS CALLOSUM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCC, 1-BP INS, 571G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs797044552,
|
|
|
|
|
|
|
|
ClinVar: RCV000192078
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 5-generation Iranian family with congenital mirror movements (MRMV1; 157600), initially described by Sharafaddinzadeh et al. (2008), Srour et al. (2010) identified insertion of a guanine at nucleotide 571 in exon 3 of the DCC gene, resulting in frameshift with a termination codon 35 amino acids later (571dupG; Val191GlyfsTer35). This mutation was absent in 538 unrelated control individuals. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 MIRROR MOVEMENTS 1 AND/OR AGENESIS OF THE CORPUS CALLOSUM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCC, 2-BP DEL, 3835CT
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs797044556,
|
|
|
|
|
|
|
|
ClinVar: RCV000192083
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 affected members of a 3-generation Italian family with congenital mirror movements (MRMV1; 157600), Depienne et al. (2011) identified a heterozygous 2-bp deletion (3835delCT) in exon 26 of the DCC gene, resulting in a frameshift and premature termination. The patients had onset in infancy or early childhood of involuntary mirror movements affecting the upper limbs and hands. Three had a stable condition; 1 had mild improvement during childhood. The mutation likely resulted in nonsense-mediated mRNA decay and haploinsufficiency. The mutation was not found in 340 control chromosomes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MIRROR MOVEMENTS 1 AND/OR AGENESIS OF THE CORPUS CALLOSUM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCC, ARG275TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs754914260,
|
|
|
|
|
|
gnomAD: rs754914260,
|
|
|
|
|
|
ClinVar: RCV000192079, RCV000416354, RCV004546447
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 7 members of a 3-generation family (family 3) with congenital mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600), Marsh et al. (2017) identified a heterozygous c.823C-T transition (c.823C-T, NM_005215.3) in the DCC gene, resulting in an arg275-to-ter (R275X) substitution in the N-terminal extracellular domain. The mutation was not found in the dbSNP, 1000 Genomes Project, or ExAC databases. The family was originally reported by Meneret et al. (2014) as having congenital mirror movements, but was not described in detail. According to the pedigree provided by Marsh et al. (2017), there were 7 confirmed mutation carriers in the family, including 2 (a male and female) with mirror movements and partial ACC, 3 (2 males and a female) with isolated mirror movements with normal brain imaging, 1 female with complete ACC and without mirror movements, and 1 unaffected female mutation carrier, indicating incomplete penetrance. Functional studies of the variant and studies of patient cells were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MIRROR MOVEMENTS 1 AND/OR AGENESIS OF THE CORPUS CALLOSUM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCC, 1-BP DEL, 925A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1057519053,
|
|
|
|
|
|
|
|
ClinVar: RCV000416317, RCV000494695
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a large multigenerational family (family 1) with congenital mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600), Marsh et al. (2017) identified a heterozygous 1-bp deletion (c.925delA, NM_005215.3) in the DCC gene, resulting in a frameshift and premature termination (Thr309ProfsTer26) in the N-terminal extracellular domain. The mutation, which was found by a combination of linkage analysis and exome sequencing, was confirmed by Sanger sequencing. It was not found in the dbSNP, 1000 Genomes Project, or ExAC databases. The mutation segregated with the disorder in the family, but there was evidence of incomplete penetrance. Functional studies of the variant and studies of patient cells were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MIRROR MOVEMENTS 1 AND/OR AGENESIS OF THE CORPUS CALLOSUM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCC, VAL793GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1057519054,
|
|
|
|
|
|
|
|
ClinVar: RCV000416336, RCV000494699
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a 3-generation family (family 2) with congenital mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600), Marsh et al. (2017) identified a heterozygous c.2378T-G transversion (c.2378T-G, NM_005215.3) in the DCC gene, resulting in a val793-to-gly (V793G) substitution in the netrin-1 binding domain. The mutation, which was found by a combination of linkage analysis and exome sequencing, was confirmed by Sanger sequencing. It was not found in the dbSNP, 1000 Genomes Project, or ExAC databases. The mutation segregated with the disorder in the family, but there was evidence of incomplete penetrance. Functional studies of the variant and studies of patient cells were not performed, but the mutation was predicted to be disruptive. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MIRROR MOVEMENTS 1 AND/OR AGENESIS OF THE CORPUS CALLOSUM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCC, GLY805GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1057519055,
|
|
|
|
|
|
|
|
ClinVar: RCV000416322, RCV000494701
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 members of a 3-generation family (family 4) with congenital mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600), Marsh et al. (2017) identified a heterozygous c.2414G-A transition (c.2414G-A, NM_005215.3) in the DCC gene, resulting in a gly805-to-glu (G805E) substitution in the netrin-1 binding domain. The mutation was found by direct sequencing and was not present in the dbSNP, 1000 Genomes Project, or ExAC databases. The mutation segregated with the disorder in the family, but there was evidence of incomplete penetrance. Functional studies of the variant and studies of patient cells were not performed, but the mutation was predicted to be disruptive. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 GAZE PALSY, FAMILIAL HORIZONTAL, WITH PROGRESSIVE SCOLIOSIS 2, WITH IMPAIRED INTELLECTUAL DEVELOPMENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCC, 7,682-BP DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000494694
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers, born of Mexican parents, with familial horizontal gaze palsy with progressive scoliosis-2 with impaired intellectual development (HGPPS2; 617542), Jamuar et al. (2017) identified a homozygous 7,682-bp deletion (chr18.49,867,185-49,874,867del, GRCh37) affecting exon 1 and intron 1 of the DCC gene. Analysis of patient cells showed that the deletion resulting in the skipping of exon 1, a frameshift, and premature termination (Pro11ThrfsTer15), resulting in a functional null allele. The deletion, which was found by a combination of homozygosity mapping and CNV analysis, was not found in the dbSNP (build 146), 1000 Genomes Project, ExAC, or Exome Variant Server databases, or in an internal exome database. The mother was a heterozygous carrier; DNA from the father was unavailable. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 GAZE PALSY, FAMILIAL HORIZONTAL, WITH PROGRESSIVE SCOLIOSIS 2, WITH IMPAIRED INTELLECTUAL DEVELOPMENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCC, 7-BP DEL, NT788
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1555682265,
|
|
|
|
|
|
|
|
ClinVar: RCV000494700
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a girl, born of consanguineous Saudi Arabian parents, with familial horizontal gaze palsy with progressive scoliosis-2 with impaired intellectual development (HGPPS2; 617542), Jamuar et al. (2017) identified a homozygous 7-bp deletion (chr18.50,450,167-50,450,173del, GRCh37) in exon 4 of the DCC gene, resulting in a frameshift and premature termination (Val263AlafsTer36) and a functional null allele. The deletion, which was found by targeted sequencing of the DCC gene, was present in the heterozygous state in each parent, but was not found in the dbSNP (build 146), 1000 Genomes Project, ExAC, or Exome Variant Server databases, or in an internal exome database of over 1,000 samples from Middle Eastern individuals. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MIRROR MOVEMENTS 1 AND/OR AGENESIS OF THE CORPUS CALLOSUM</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DCC, 1-BP DUP, 2774A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2145024323,
|
|
|
|
|
|
|
|
ClinVar: RCV001731260
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 patients from 2 generations of an Ethiopian Jewish family with congenital mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600), Sagi-Dain et al. (2020) identified heterozygosity for a 1-bp duplication (c.2774dupA, NM_005215) in the DCC gene, predicted to result in a frameshift and premature termination (Asn925LysfsTer17). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. The mutation was also identified in an asymptomatic female family member. A fetus with agenesis of the corpus callosum from a terminated pregnancy in this family was not tested for the mutation. The mutation was not present in the dbSNP or gnomAD databases or in an in-house database. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bowman, B. M., Wildrick, D. M., Alfaro, S. R.
|
|
<strong>Chromosome 18 allele loss at the D18S6 locus in human colorectal carcinomas.</strong>
|
|
Biochem. Biophys. Res. Commun. 155: 463-469, 1988.
|
|
|
|
|
|
[PubMed: 3415702]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0006-291x(88)81109-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Castets, M., Broutier, L., Molin, Y., Brevet, M., Chazot, G., Gadot, N., Paquet, A., Mazelin, L., Jarroson-Wuilleme, L., Scoazec, J.-Y., Bernet, A., Mehlen, P.
|
|
<strong>DCC constrains tumour progression via its dependence receptor activity.</strong>
|
|
Nature 482: 534-537, 2011.
|
|
|
|
|
|
[PubMed: 22158121]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature10708]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chan, S. S.-Y., Zheng, H., Su, M.-W., Wilk, R., Killeen, M. T., Hedgecock, E. M., Culotti, J. G.
|
|
<strong>UNC-40, a C. elegans homolog of the DCC (deleted in colorectal cancer), is required in motile cells responding to UNC-6 netrin cues.</strong>
|
|
Cell 87: 187-195, 1996.
|
|
|
|
|
|
[PubMed: 8861903]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)81337-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cho, K. R., Oliner, J. D., Simons, J. W., Hedrick, L., Fearon, E. R., Preisinger, A. C., Hedge, P., Silverman, G. A., Vogelstein, B.
|
|
<strong>The DCC gene: structural analysis and mutations in colorectal carcinomas.</strong>
|
|
Genomics 19: 525-531, 1994.
|
|
|
|
|
|
[PubMed: 8188295]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1994.1102]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Colon-Ramos, D. A., Margeta, M. A., Shen, K.
|
|
<strong>Glia promote local synaptogenesis through UNC-6 (netrin) signaling in C. elegans.</strong>
|
|
Science 318: 103-106, 2007.
|
|
|
|
|
|
[PubMed: 17916735]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1143762]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Depienne, C., Cincotta, M., Billot, S., Bouteiller, D., Groppa, S., Brochard, V., Flamand, C., Hubsch, C., Meunier, S., Giovannelli, F., Klebe, S., Corvol, J. C., Vidailhet, M., Brice, A., Roze, E.
|
|
<strong>A novel DCC mutation and genetic heterogeneity in congenital mirror movements.</strong>
|
|
Neurology 76: 260-264, 2011.
|
|
|
|
|
|
[PubMed: 21242494]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0b013e318207b1e0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fazeli, A., Dickinson, S. L., Hermiston, M. L., Tighe, R. V., Steen, R. G., Small, C. G., Stoeckli, E. T., Keino-Masu, K., Masu, M., Rayburn, H., Simons, J., Bronson, R. T., Gordon, J. I., Tessier-Lavigne, M., Weinberg, R. A.
|
|
<strong>Phenotype of mice lacking functional Deleted in colorectal cancer (Dcc) gene.</strong>
|
|
Nature 386: 796-804, 1997.
|
|
|
|
|
|
[PubMed: 9126737]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/386796a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fearon, E. R., Cho, K. R., Nigro, J. M., Kern, S. E., Simons, J. W., Ruppert, J. M., Hamilton, S. R., Preisinger, A. C., Thomas, G., Kinzler, K. W., Vogelstein, B.
|
|
<strong>Identification of a chromosome 18q gene that is altered in colorectal cancers.</strong>
|
|
Science 247: 49-56, 1990.
|
|
|
|
|
|
[PubMed: 2294591]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.2294591]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Finger, J. H., Bronson, R. T., Harris, B., Johnson, K., Przyborski, S. A., Ackerman, S. L.
|
|
<strong>The Netrin 1 receptors Unc5h3 and Dcc are necessary at multiple choice points for the guidance of corticospinal tract axons.</strong>
|
|
J. Neurosci. 22: 10346-10356, 2002.
|
|
|
|
|
|
[PubMed: 12451134]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1523/JNEUROSCI.22-23-10346.2002]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Forcet, C., Stein, E., Pays, L., Corset, V., Llambi, F., Tessier-Lavigne, M., Mehlen, P.
|
|
<strong>Netrin-1-mediated axon outgrowth requires deleted in colorectal cancer-dependent MAPK activation.</strong>
|
|
Nature 417: 443-447, 2002.
|
|
|
|
|
|
[PubMed: 11986622]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature748]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Galko, M. J., Tessier-Lavigne, M.
|
|
<strong>Function of an axonal chemoattractant modulated by metalloprotease activity.</strong>
|
|
Science 289: 1365-1367, 2000.
|
|
|
|
|
|
[PubMed: 10958786]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.289.5483.1365]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gotley, D. C., Reeder, J. A., Fawcett, J., Walsh, M. D., Bates, P., Simmons, D. L., Antalis, T. M.
|
|
<strong>The deleted in colon cancer (DCC) gene is consistently expressed in colorectal cancers and metastases.</strong>
|
|
Oncogene 13: 787-795, 1996.
|
|
|
|
|
|
[PubMed: 8761300]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hohne, M. W., Halatsch, M.-E., Kahl, G. F., Weinel, R. J.
|
|
<strong>Frequent loss of expression of the potential tumor suppressor gene DCC in ductal pancreatic adenocarcinoma.</strong>
|
|
Cancer Res. 52: 2616-2619, 1992.
|
|
|
|
|
|
[PubMed: 1314700]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jamuar, S. S., Schmitz-Abe, K., D'Gama, A. M., Drottar, M., Chan, W.-M., Peeva, M., Servattalab, S., Lam, A.-T. N., Delgado, M. R., Clegg, N. J., Al Zayed, Z., Dogar, M. A., and 14 others.
|
|
<strong>Biallelic mutations in human DCC cause developmental split-brain syndrome.</strong>
|
|
Nature Genet. 49: 606-612, 2017.
|
|
|
|
|
|
[PubMed: 28250456]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.3804]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jen, J., Kim, H., Piantadosi, S., Liu, Z.-F., Levitt, R. C., Sistonen, P., Kinzler, K. W., Vogelstein, B., Hamilton, S. R.
|
|
<strong>Allelic loss of chromosome 18q and prognosis in colorectal cancer.</strong>
|
|
New Eng. J. Med. 331: 213-221, 1994.
|
|
|
|
|
|
[PubMed: 8015568]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199407283310401]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Justice, M. J., Gilbert, D. J., Kinzler, K. W., Vogelstein, B., Buchberg, A. M., Ceci, J. D., Matsuda, Y., Chapman, V. M., Patriotis, C., Makris, A., Tsichlis, P. N., Jenkins, N. A., Copeland, N. G.
|
|
<strong>A molecular genetic linkage map of mouse chromosome 18 reveals extensive linkage conservation with human chromosomes 5 and 18.</strong>
|
|
Genomics 13: 1281-1288, 1992.
|
|
|
|
|
|
[PubMed: 1354644]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(92)90047-v]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Keino-Masu, K., Masu, M., Hinck, L., Leonardo, E. D., Chan, S. S.-Y., Culotti, J. G., Tessier-Lavigne, M.
|
|
<strong>Deleted in colorectal cancer (DCC) encodes a netrin receptor.</strong>
|
|
Cell 87: 175-185, 1996.
|
|
|
|
|
|
[PubMed: 8861902]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)81336-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Keynes, R., Cook, G. M. W.
|
|
<strong>Axon guidance molecules.</strong>
|
|
Cell 83: 161-169, 1995.
|
|
|
|
|
|
[PubMed: 7585933]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(95)90157-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kolodziej, P. A., Timpe, L. C., Mitchell, K. J., Fried, S. R., Goodman, C. S., Jan, L. Y., Jan, Y. N.
|
|
<strong>Frazzled encodes a Drosophila member of the DCC immunoglobulin subfamily and is required for CNS and motor axon guidance.</strong>
|
|
Cell 87: 197-204, 1996.
|
|
|
|
|
|
[PubMed: 8861904]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)81338-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Krimpenfort, P., Song, J.-Y., Proost, N., Zevenhoven, J., Jonkers, J., Berns, A.
|
|
<strong>Deleted in colorectal carcinoma suppresses metastasis in p53-deficient mammary tumours.</strong>
|
|
Nature 482: 538-541, 2012.
|
|
|
|
|
|
[PubMed: 22358843]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature10790]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, W., Lee, J., Vikis, H. G., Lee, S.-H., Liu, G., Aurandt, J., Shen, T.-L., Fearon, E. R., Guan, J.-L., Han, M., Rao, Y., Hong, K., Guan, K.-L.
|
|
<strong>Activation of FAK and Src are receptor-proximal events required for netrin signaling.</strong>
|
|
Nature Neurosci. 7: 1213-1221, 2004.
|
|
|
|
|
|
[PubMed: 15494734]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nn1329]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Liu, G., Beggs, H., Jurgensen, C., Park, H.-T., Tang, H., Gorski, J., Jones, K. R., Reichardt, L. F., Wu, J., Rao, Y.
|
|
<strong>Netrin requires focal adhesion kinase and Src family kinases for axon outgrowth and attraction.</strong>
|
|
Nature Neurosci. 7: 1222-1232, 2004.
|
|
|
|
|
|
[PubMed: 15494732]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nn1331]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lynch, H. T., Schuelke, G. S., Kimberling, W. J., Albano, W. A., Lynch, J. F., Biscone, K. A., Lipkin, M. L., Deschner, E. E., Mikol, Y. B., Sandberg, A. A., Elston, R. C., Bailey-Wilson, J. E., Danes, B. S.
|
|
<strong>Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). II. Biomarker studies.</strong>
|
|
Cancer 56: 939-951, 1985.
|
|
|
|
|
|
[PubMed: 4016686]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1097-0142(19850815)56:4<939::aid-cncr2820560440>3.0.co;2-t]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maesawa, C., Tamura, G., Ogasawara, S., Suzuki, Y., Sakata, K., Sugimura, J., Nishizuka, S., Sato, N., Ishida, K., Saito, K., Satodate, R.
|
|
<strong>Loss of heterozygosity at the DCC gene locus is not crucial for the acquisition of metastatic potential in oesophageal squamous cell carcinoma.</strong>
|
|
Europ. J. Cancer. 32A: 896-898, 1996.
|
|
|
|
|
|
[PubMed: 9081374]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0959-8049(96)00010-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Marsh, A. P. L., Heron, D., Edwards, T. J., Quartier, A., Galea, C., Nava, C., Rastetter, A., Moutard, M.-L., Anderson, V., Bitoun, P., Bunt, J., Faudet, A., and 41 others.
|
|
<strong>Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance.</strong>
|
|
Nature Genet. 49: 511-514, 2017.
|
|
|
|
|
|
[PubMed: 28250454]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.3794]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mazelin, L., Bernet, A., Bonod-Bidaud, C., Pays, L., Arnaud, S., Gespach, C., Bredesen, D. E., Scoazec, J.-Y., Mehlen, P.
|
|
<strong>Netrin-1 controls colorectal tumorigenesis by regulating apoptosis.</strong>
|
|
Nature 431: 80-84, 2004.
|
|
|
|
|
|
[PubMed: 15343335]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature02788]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mehlen, P., Rabizadeh, S., Snipas, S. J., Assa-Munt, N., Salvesen, G. S., Bredesen, D. E.
|
|
<strong>The DCC gene produce induces apoptosis by a mechanism requiring receptor proteolysis.</strong>
|
|
Nature 395: 801-804, 1998.
|
|
|
|
|
|
[PubMed: 9796814]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/27441]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meneret, A., Depienne, C., Riant, F., Trouillard, O., Bouteiller, D., Cincotta, M., Bitoun, P., Wickert, J., Lagroua, I., Westenberger, A., Borgheresi, A., Doummar, D., and 18 others.
|
|
<strong>Congenital mirror movements: mutational analysis of RAD51 and DCC in 26 cases.</strong>
|
|
Neurology 82: 1999-2002, 2014.
|
|
|
|
|
|
[PubMed: 24808016]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0000000000000477]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Miyake, S., Nagai, K., Yoshino, K., Oto, M., Endo, M., Yuasa, Y.
|
|
<strong>Point mutations and allelic deletion of tumor suppressor gene DCC in human esophageal squamous cell carcinomas and their relation to metastasis.</strong>
|
|
Cancer Res. 54: 3007-3010, 1994.
|
|
|
|
|
|
[PubMed: 8187090]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nigro, J. M., Cho, K. R., Fearon, E. R., Kern, S. E., Ruppert, J. M., Oliner, J. D., Kinzler, K. W., Vogelstein, B.
|
|
<strong>Scrambled exons.</strong>
|
|
Cell 64: 607-613, 1991.
|
|
|
|
|
|
[PubMed: 1991322]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(91)90244-s]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nishiyama, M., Hoshino, A., Tsai, L., Henley, J. R., Goshima, Y., Tessier-Lavigne, M., Poo, M., Hong, K.
|
|
<strong>Cyclic AMP/GMP-dependent modulation of Ca(2+) channels sets the polarity of nerve growth-cone turning.</strong>
|
|
Nature 423: 990-995, 2003.
|
|
|
|
|
|
[PubMed: 12827203]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature01751]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ren, X., Ming, G., Xie, Y., Hong, Y., Sun, D., Zhao, Z., Feng, Z., Wang, Q., Shim, S., Chen, Z., Song, H., Mei, L., Xiong, W.
|
|
<strong>Focal adhesion kinase in netrin-1 signaling.</strong>
|
|
Nature Neurosci. 7: 1204-1212, 2004.
|
|
|
|
|
|
[PubMed: 15494733]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nn1330]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sagi-Dain, L., Kurolap, A., Ilivitzki, A., Mory, A., Paperna, T., Regeneron Genetics Center, Kedar, R., Gonzaga-Jauregui, C., Peleg, A., Feldman, H. B.
|
|
<strong>A novel heterozygous loss-of-function DCC netrin 1 receptor variant in prenatal agenesis of corpus callosum and review of the literature.</strong>
|
|
Am. J. Med. Genet. 182A: 205-212, 2020.
|
|
|
|
|
|
[PubMed: 31697046]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.61404]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sharafaddinzadeh, N., Bavarsad, R., Yousefkhah, M., Aleali, A. M.
|
|
<strong>Familial mirror movements over five generations. (Letter)</strong>
|
|
Neurology India 56: 482-483, 2008.
|
|
|
|
|
|
[PubMed: 19127048]
|
|
|
|
|
|
[Full Text: https://doi.org/10.4103/0028-3886.44813]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shi, M., Guo, C., Dai, J.-X., Ding, Y.-Q.
|
|
<strong>DCC is required for the tangential migration of noradrenergic neurons in locus coeruleus of mouse brain.</strong>
|
|
Molec. Cell. Neurosci. 39: 529-538, 2008. Note: Erratum: Molec. Cell. Neurosci. 45: 84 only, 2010.
|
|
|
|
|
|
[PubMed: 18771734]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.mcn.2008.07.023]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shibata, D., Reale, M. A., Lavin, P., Silverman, M., Fearon, E. R., Steele, G., Jr., Jessup, J. M., Loda, M., Summerhayes, I. C.
|
|
<strong>The DCC protein and prognosis in colorectal cancer.</strong>
|
|
New Eng. J. Med. 335: 1727-1732, 1996.
|
|
|
|
|
|
[PubMed: 8929264]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199612053352303]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Srour, M., Riviere, J.-B., Pham, J. M. T., Dube, M.-P., Girard, S., Morin, S., Dion, P. A., Asselin, G., Rochefort, D., Hince, P., Diab, S., Sharafaddinzadeh, N., Chouinard, S., Theoret, H., Charron, F., Rouleau, G. A.
|
|
<strong>Mutations in DCC cause congenital mirror movements.</strong>
|
|
Science 328: 592 only, 2010.
|
|
|
|
|
|
[PubMed: 20431009]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1186463]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stein, E., Tessier-Lavigne, M.
|
|
<strong>Hierarchical organization of guidance receptors: silencing of netrin attraction by Slit through a Robo/DCC receptor complex.</strong>
|
|
Science 291: 1928-1938, 2001. Note: Expression of Concern: Science 378: 1284 only, 2022.
|
|
|
|
|
|
[PubMed: 11239147]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1058445]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stein, E., Zou, Y., Poo, M., Tessier-Lavigne, M.
|
|
<strong>Binding of DCC by netrin-1 to mediate axon guidance independent of adenosine A2B receptor activation.</strong>
|
|
Science 291: 1976-1982, 2001. Note: Expression of Concern: Science 378: 1284 only, 2022.
|
|
|
|
|
|
[PubMed: 11239160]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1059391]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tanaka, K., Oshimura, M., Kikuchi, R., Seki, M., Hayashi, T., Miyaki, M.
|
|
<strong>Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 5 or 18.</strong>
|
|
Nature 349: 340-342, 1991.
|
|
|
|
|
|
[PubMed: 1670965]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/349340a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tcherkezian, J., Brittis, P. A., Thomas, F., Roux, P. P., Flanagan, J. G.
|
|
<strong>Transmembrane receptor DCC associates with protein synthesis machinery and regulates translation.</strong>
|
|
Cell 141: 632-644, 2010. Note: Erratum: Cell 184: 2520 only, 2021.
|
|
|
|
|
|
[PubMed: 20434207]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2010.04.008]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thiagalingam, S., Lengauer, C., Leach, F. S., Schutte, M., Hahn, S. A., Overhauser, J., Willson, J. K. V., Markowitz, S., Hamilton, S. R., Kern, S. E., Kinzler, K. W., Vogelstein, B.
|
|
<strong>Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers.</strong>
|
|
Nature Genet. 13: 343-346, 1996.
|
|
|
|
|
|
[PubMed: 8673134]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0796-343]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Uchino, S., Tsuda, H., Noguchi, M., Yokota, J., Terada, M., Saito, T., Kobayashi, M., Sugimura, T., Hirohashi, S.
|
|
<strong>Frequent loss of heterozygosity at the DCC locus in gastric cancer.</strong>
|
|
Cancer Res. 52: 3099-3102, 1992.
|
|
|
|
|
|
[PubMed: 1591722]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vogelstein, B., Fearon, E. R., Hamilton, S. R., Kern, S. E., Preisinger, A. C., Leppert, M., Nakamura, Y., White, R., Smits, A. M. M., Bos, J. L.
|
|
<strong>Genetic alterations during colorectal-tumor development.</strong>
|
|
New Eng. J. Med. 319: 525-532, 1988.
|
|
|
|
|
|
[PubMed: 2841597]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198809013190901]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vogelstein, B.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 11/30/1995.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wei, X., Walia, V., Lin, J. C., Teer, J. K., Prickett, T. D., Gartner, J., Davis, S., NISC Comparative Sequencing Program, Stemke-Hale, K., Davies, M. A., Gershenwald, J. E., Robinson, W., Robinson, S., Rosenberg, S. A., Samuels, Y.
|
|
<strong>Exome sequencing identifies GRIN2A as frequently mutated in melanoma.</strong>
|
|
Nature Genet. 43: 442-446, 2011.
|
|
|
|
|
|
[PubMed: 21499247]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.810]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Xu, K., Wu, Z., Renier, N., Antipenko, A., Tzvetkova-Robev, D., Xu, Y., Minchenko, M., Nardi-Dei, V., Rajashankar, K. R., Himanen, J., Tessier-Lavigne, M., Nikolov, D. B.
|
|
<strong>Structures of netrin-1 bound to two receptors provide insight into its axon guidance mechanism.</strong>
|
|
Science 344: 1275-1279, 2014.
|
|
|
|
|
|
[PubMed: 24876346]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1255149]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zetter, B. R.
|
|
<strong>Adhesion molecules in tumor metastasis.</strong>
|
|
Semin. Cancer Biol. 4: 219-229, 1993.
|
|
|
|
|
|
[PubMed: 8400144]
|
|
|
|
|
|
|
|
</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">
|
|
Hilary J. Vernon - updated : 10/22/2021<br>Cassandra L. Kniffin - updated : 06/28/2017<br>Ada Hamosh - updated : 7/7/2014<br>Ada Hamosh - updated : 3/13/2012<br>Cassandra L. Kniffin - updated : 5/12/2011<br>Cassandra L. Kniffin - updated : 4/14/2011<br>Patricia A. Hartz - updated : 12/14/2010<br>Patricia A. Hartz - updated : 6/3/2010<br>Ada Hamosh - updated : 6/3/2010<br>Ada Hamosh - updated : 10/26/2007<br>Cassandra L. Kniffin - updated : 2/17/2005<br>Ada Hamosh - updated : 11/10/2004<br>Ada Hamosh - updated : 7/8/2003<br>Paul J. Converse - updated : 5/6/2002<br>Ada Hamosh - updated : 3/27/2001<br>Ada Hamosh - updated : 3/27/2001<br>Ada Hamosh - updated : 9/5/2000<br>Victor A. McKusick - updated : 10/22/1998<br>Jennifer P. Macke - updated : 7/11/1997<br>Victor A. McKusick - updated : 6/27/1997<br>Moyra Smith - updated : 7/4/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 2/26/1988
|
|
</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 : 04/15/2024<br>carol : 01/21/2023<br>carol : 01/21/2023<br>carol : 11/05/2021<br>carol : 10/22/2021<br>alopez : 01/27/2021<br>carol : 04/02/2019<br>ckniffin : 04/02/2019<br>carol : 04/24/2018<br>carol : 10/27/2017<br>carol : 07/05/2017<br>carol : 07/03/2017<br>carol : 07/03/2017<br>ckniffin : 06/28/2017<br>alopez : 10/07/2016<br>carol : 07/08/2014<br>alopez : 7/7/2014<br>carol : 9/18/2013<br>terry : 9/25/2012<br>alopez : 3/14/2012<br>terry : 3/13/2012<br>carol : 5/13/2011<br>ckniffin : 5/12/2011<br>wwang : 5/3/2011<br>ckniffin : 4/14/2011<br>mgross : 1/4/2011<br>terry : 12/14/2010<br>alopez : 8/31/2010<br>alopez : 6/6/2010<br>terry : 6/3/2010<br>terry : 6/3/2010<br>ckniffin : 2/5/2008<br>ckniffin : 1/16/2008<br>alopez : 11/1/2007<br>terry : 10/26/2007<br>alopez : 7/5/2007<br>wwang : 2/17/2005<br>tkritzer : 11/10/2004<br>mgross : 7/14/2003<br>mgross : 7/14/2003<br>terry : 7/8/2003<br>tkritzer : 6/19/2003<br>alopez : 6/7/2002<br>mgross : 5/6/2002<br>alopez : 3/27/2001<br>alopez : 3/27/2001<br>alopez : 9/5/2000<br>alopez : 10/22/1998<br>terry : 10/22/1998<br>carol : 7/30/1998<br>jenny : 9/2/1997<br>jenny : 8/14/1997<br>jenny : 7/2/1997<br>terry : 6/27/1997<br>mark : 1/6/1997<br>terry : 1/3/1997<br>mark : 12/20/1996<br>mark : 12/20/1996<br>terry : 12/10/1996<br>terry : 12/9/1996<br>terry : 9/17/1996<br>marlene : 8/15/1996<br>mark : 7/5/1996<br>mark : 7/4/1996<br>mark : 12/18/1995<br>mark : 12/15/1995<br>terry : 12/6/1995<br>carol : 11/18/1994<br>terry : 8/25/1994<br>carol : 12/22/1993<br>carol : 12/17/1993<br>carol : 3/29/1993<br>carol : 11/3/1992
|
|
</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>
|
|
|
|
|