4500 lines
363 KiB
Text
4500 lines
363 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
|
|
|
|
- *190181 - TRANSFORMING GROWTH FACTOR-BETA RECEPTOR, TYPE I; TGFBR1
|
|
|
|
|
|
- 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=190181"><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">*190181</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/190181">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=ENSG00000106799;t=ENST00000374994" 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=7046" 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=190181" 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=ENSG00000106799;t=ENST00000374994" 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_001130916,NM_001306210,NM_001407416,NM_001407417,NM_001407418,NM_001407419,NM_001407420,NM_001407422,NM_001407423,NM_001407424,NM_001407425,NM_001407426,NM_001407427,NM_001407428,NM_001407429,NM_001407430,NM_001407432,NM_001407433,NM_001407434,NM_001407435,NM_001407436,NM_001407437,NM_001407438,NM_004612,NR_176360,NR_176361,NR_176362,NR_176363,XM_011518948" 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_004612" 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=190181" 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=01822&isoform_id=01822_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/TGFBR1" 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/431035,547777,3003038,4104447,4759226,39843079,40204908,47937325,88604813,119579309,119579310,143023841,143023843,194378568,194378846,195963412,254257711,270048020,333756554,767958123,817050443,2247445819,2247445852,2247445859,2247445871,2247445873,2247445879,2247445885,2247445888,2247445890,2247445892,2247445896,2247445907,2247445952,2247445958,2247445964,2247445970,2247445974,2247445991,2247445999,2247446010,2247446019,2462626128" 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/P36897" 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=7046" 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=ENSG00000106799;t=ENST00000374994" 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=TGFBR1" 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=TGFBR1" 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+7046" 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/TGFBR1" 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:7046" 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/7046" 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=chr9&hgg_gene=ENST00000374994.9&hgg_start=99103647&hgg_end=99154192&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:11772" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:11772" 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/tgfbr1" 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=190181[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=190181[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/TGFBR1/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/ENSG00000106799" 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=TGFBR1" 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=TGFBR1" 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=TGFBR1" 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=TGFBR1&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/PA36485" 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:11772" 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/FBgn0011300.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:98728" 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/TGFBR1#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:98728" 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/7046/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=7046" 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="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
|
|
<div id="mimWormbaseGeneFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00000897;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00000897 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00004860;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00004860 </a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-051120-75" 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:7046" 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=TGFBR1&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>
|
|
190181
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
TRANSFORMING GROWTH FACTOR-BETA RECEPTOR, TYPE I; TGFBR1
|
|
|
|
</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">
|
|
ACTIVIN RECEPTOR-LIKE KINASE 5; ALK5
|
|
</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=TGFBR1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">TGFBR1</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/9/355?start=-3&limit=10&highlight=355">9q22.33</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr9:99103647-99154192&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'})">9:99,103,647-99,154,192</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=132800,609192" 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="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/9/355?start=-3&limit=10&highlight=355">
|
|
9q22.33
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
{Multiple self-healing squamous epithelioma, susceptibility to}
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/132800"> 132800 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Loeys-Dietz syndrome 1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/609192"> 609192 </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/190181" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/190181" 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 TGFBR1 gene encodes a serine/threonine kinase receptor for transforming growth factor-beta (TGFB1; <a href="/entry/190180">190180</a>). Most growth factor receptors are transmembrane tyrosine kinases or are associated with cytoplasmic tyrosine kinases. Another class of transmembrane receptors, however, is predicted to function as serine/threonine kinases. On the basis of their various biologic activities, different species of TGF-beta are probably potent developmental regulators of cell proliferation and differentiation. Several types of TGF-beta-binding proteins have been detected at the cell surface. Type I and type II receptors are defined on the basis of the mobility of their (125)I-TGF-beta cross-linked products in denaturing gels. These receptors probably mediate most activities of TGF-beta. The type II receptor (TGFBR2; <a href="/entry/190182">190182</a>) functions as a transmembrane serine/threonine kinase and is required for the antiproliferative activity of TGF-beta, whereas the type I receptor mediates the induction of several genes involved in cell-matrix interactions (summary by <a href="#5" class="mim-tip-reference" title="Ebner, R., Chen, R.-H., Shum, L., Lawler, S., Zioncheck, T. F., Lee, A., Lopez, A. R., Derynck, R. <strong>Cloning of a type I TGF-beta receptor and its effect on TGF-beta binding to the type II receptor.</strong> Science 260: 1344-1348, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8388127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8388127</a>] [<a href="https://doi.org/10.1126/science.8388127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8388127">Ebner et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8388127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#5" class="mim-tip-reference" title="Ebner, R., Chen, R.-H., Shum, L., Lawler, S., Zioncheck, T. F., Lee, A., Lopez, A. R., Derynck, R. <strong>Cloning of a type I TGF-beta receptor and its effect on TGF-beta binding to the type II receptor.</strong> Science 260: 1344-1348, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8388127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8388127</a>] [<a href="https://doi.org/10.1126/science.8388127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8388127">Ebner et al. (1993)</a> cloned a murine serine/threonine kinase receptor that shares a conserved extracellular domain with the type II TGF-beta receptor. Overexpression of this receptor alone did not increase cell surface binding of TGF-beta, but coexpression with the type II TGF-beta receptor caused TGF-beta to bind to this receptor, which had the size of the type I TGF-beta receptor. Overexpression of this newly cloned receptor inhibited binding of TGF-beta to the type II receptor in a dominant-negative fashion. Combinatorial interactions and stoichiometric ratios between the type I and II receptors may therefore determine the extent of TGF-beta binding and the resulting biologic activities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8388127" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By PCR analysis on human erythroleukemia cell cDNA using degenerate primers based on conserved regions of ser/thr kinase receptors, <a href="#7" class="mim-tip-reference" title="Franzen, P., ten Dijke, P., Ichijo, H., Yamashita, H., Schulz, P., Heldin, C.-H., Miyazono, K. <strong>Cloning of a TGF-beta type I receptor that forms a heteromeric complex with the TGF-beta type II receptor.</strong> Cell 75: 681-692, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8242743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8242743</a>] [<a href="https://doi.org/10.1016/0092-8674(93)90489-d" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8242743">Franzen et al. (1993)</a> isolated a cDNA encoding TGFBR1, which they called ALK5 (activin receptor-like kinase-5). The deduced 503-amino acid, 53-kD TGFBR1 ser/thr kinase contains a signal peptide; an extracellular cysteine-rich region with a single N-glycosylation site; a transmembrane region; and a putative cytoplasmic protein kinase domain. SDS-PAGE analysis showed that immunoprecipitation of TGFBR1 incubated with labeled TGFB1 produced a 70-kD complex as well as a heteromeric 94-kD TGFBR2 complex. Northern blot analysis detected a 5.5-kb TGFBR1 transcript in all tissues tested, with highest expression in placenta and lowest expression in brain and heart. Transient expression of TGFBR1 in a receptor-negative cell line led to the production of plasminogen activator inhibitor-1 (PAI1; <a href="/entry/173360">173360</a>) in response to stimulation with TGFB1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8242743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>TGFB1 regulates cell cycle progression by a unique signaling mechanism that involves its binding to TGFBR2 and activation of TGFBR1. Both are transmembrane serine/threonine receptor kinases. The TGFBR1 receptor may be inactivated in many of the cases of human tumor cells refractory to TGFB-mediated cell cycle arrest. <a href="#22" class="mim-tip-reference" title="Vellucci, V. F., Reiss, M. <strong>Cloning and genomic organization of the human transforming growth factor-beta type I receptor gene.</strong> Genomics 46: 278-283, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9417915/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9417915</a>] [<a href="https://doi.org/10.1006/geno.1997.5023" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9417915">Vellucci and Reiss (1997)</a> reported that the TGFBR1 gene is approximately 31 kb long and contains 9 exons. The organization of the segment of the gene that encodes the C-terminal portion of the serine/threonine kinase domain appears to be highly conserved among members of the gene family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9417915" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#11" class="mim-tip-reference" title="Johnson, D. W., Qumsiyeh, M., Benkhalifa, M., Marchuk, D. A. <strong>Assignment of human transforming growth factor-beta type I and type III receptor genes (TGFBR1 and TGFBR3) to 9q33-q34 and 1p32-p33, respectively.</strong> Genomics 28: 356-357, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8530052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8530052</a>] [<a href="https://doi.org/10.1006/geno.1995.1157" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8530052">Johnson et al. (1995)</a> used PCR with a hybrid cell DNA panel and FISH to localize the TGFBR1 gene to chromosome 9q33-q34. By FISH, <a href="#18" class="mim-tip-reference" title="Pasche, B., Luo, Y., Rao, P. H., Nimer, S. D., Dmitrovsky, E., Caron, P., Luzzatto, L., Offit, K., Cordon-Cardo, C., Renault, B., Satagopan, J. M., Murty, V. V., Massague, J. <strong>Type I transforming growth factor beta receptor maps to 9q22 and exhibits a polymorphism and a rare variant within a polyalanine tract.</strong> Cancer Res. 58: 2727-2732, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9661882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9661882</a>]" pmid="9661882">Pasche et al. (1998)</a> localized the gene to chromosome 9q22. <a href="#12" class="mim-tip-reference" title="Kuan, J., Kono, D. H. <strong>Tgfbr1 maps to chromosome 4.</strong> Mammalian Genome 9: 95-96, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9434964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9434964</a>] [<a href="https://doi.org/10.1007/s003359900695" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9434964">Kuan and Kono (1998)</a> mapped the Tgfbr1 gene to mouse chromosome 4. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9434964+8530052+9661882" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#23" class="mim-tip-reference" title="Wang, T., Donahoe, P. K., Zervos, A. S. <strong>Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12.</strong> Science 265: 674-676, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7518616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7518616</a>] [<a href="https://doi.org/10.1126/science.7518616" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7518616">Wang et al. (1994)</a> reported that the type I receptor may be a natural ligand for immunophilin FKBP12 (<a href="/entry/186945">186945</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7518616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 membrane-bound protein encoded by TGFBR1 binds TGF-beta and forms a heterodimeric complex with the TGF-beta II receptor (<a href="#7" class="mim-tip-reference" title="Franzen, P., ten Dijke, P., Ichijo, H., Yamashita, H., Schulz, P., Heldin, C.-H., Miyazono, K. <strong>Cloning of a TGF-beta type I receptor that forms a heteromeric complex with the TGF-beta type II receptor.</strong> Cell 75: 681-692, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8242743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8242743</a>] [<a href="https://doi.org/10.1016/0092-8674(93)90489-d" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8242743">Franzen et al., 1993</a>; <a href="#11" class="mim-tip-reference" title="Johnson, D. W., Qumsiyeh, M., Benkhalifa, M., Marchuk, D. A. <strong>Assignment of human transforming growth factor-beta type I and type III receptor genes (TGFBR1 and TGFBR3) to 9q33-q34 and 1p32-p33, respectively.</strong> Genomics 28: 356-357, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8530052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8530052</a>] [<a href="https://doi.org/10.1006/geno.1995.1157" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8530052">Johnson et al., 1995</a>). Ligand binding by TGF-beta I receptors is dependent on coexpression with type II receptors. Type II receptors alone can bind ligand, but require association with type I receptors for activation of their kinase (signaling) function. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8530052+8242743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>TGFB stimulation leads to phosphorylation and activation of SMAD2 (<a href="/entry/601366">601366</a>) and SMAD3 (<a href="/entry/603109">603109</a>), which form complexes with SMAD4 (<a href="/entry/600993">600993</a>) that accumulate in the nucleus and regulate transcription of target genes. <a href="#10" class="mim-tip-reference" title="Inman, G. J., Nicolas, F. J., Hill, C. S. <strong>Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-beta receptor activity.</strong> Molec. Cell 10: 283-294, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12191474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12191474</a>] [<a href="https://doi.org/10.1016/s1097-2765(02)00585-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12191474">Inman et al. (2002)</a> demonstrated that following TGFB stimulation of epithelial cells, receptors remain active for at least 3 to 4 hours, and continuous receptor activity is required to maintain active SMADs in the nucleus and for TGFB-induced transcription. Continuous nucleocytoplasmic shuttling of the SMADs during active TGFB signaling provides the mechanism whereby the intracellular transducers of the signal continuously monitor receptor activity. These data explain how, at all times, the concentration of active SMADs in the nucleus is directly dictated by the levels of activated receptors in the cytoplasm. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12191474" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Barrios-Rodiles, M., Brown, K. R., Ozdamar, B., Bose, R., Liu, Z., Donovan, R. S., Shinjo, F., Liu, Y., Dembowy, J., Taylor, I. W., Luga, V., Przulj, N., Robinson, M., Suzuki, H., Hayashizaki, Y., Jurisica, I., Wrana, J. L. <strong>High-throughput mapping of a dynamic signaling network in mammalian cells.</strong> Science 307: 1621-1625, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15761153/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15761153</a>] [<a href="https://doi.org/10.1126/science.1105776" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15761153">Barrios-Rodiles et al. (2005)</a> developed LUMIER (luminescence-based mammalian interactome mapping), an automated high-throughput technology, to map protein-protein interaction networks systematically in mammalian cells and applied it to the TGFB pathway. Analysis using self-organizing maps and k-means clustering identified links of the TGF-beta pathway to the p21-activated kinase (PAK; see <a href="/entry/602590">602590</a>) network, to the polarity complex, and to occludin (<a href="/entry/602876">602876</a>), a structural component of tight junctions. <a href="#2" class="mim-tip-reference" title="Barrios-Rodiles, M., Brown, K. R., Ozdamar, B., Bose, R., Liu, Z., Donovan, R. S., Shinjo, F., Liu, Y., Dembowy, J., Taylor, I. W., Luga, V., Przulj, N., Robinson, M., Suzuki, H., Hayashizaki, Y., Jurisica, I., Wrana, J. L. <strong>High-throughput mapping of a dynamic signaling network in mammalian cells.</strong> Science 307: 1621-1625, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15761153/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15761153</a>] [<a href="https://doi.org/10.1126/science.1105776" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15761153">Barrios-Rodiles et al. (2005)</a> showed the occludin regulates TGFBR1 localization for efficient TGF-beta-dependent dissolution of tight junctions during epithelial-mesenchymal transitions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15761153" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Studying a Caucasian-dominated population in the U.S., <a href="#21" class="mim-tip-reference" title="Valle, L., Serena-Acedo, T., Liyanarachchi, S., Hampel, H., Comeras, I., Li, Z., Zeng, Q., Zhang, H.-T., Pennison, M. J., Sadim, M., Pasche, B., Tanner, S. M., de la Chapelle, A. <strong>Germline allele-specific expression of TGFBR1 confers an increased risk of colorectal cancer.</strong> Science 321: 1361-1365, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18703712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18703712</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18703712[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.1159397" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18703712">Valle et al. (2008)</a> showed that germline allele-specific expression (ASE) of the TGFBR1 gene is a quantitative trait that occurs in 10 to 20% of CRC patients and 1 to 3% of controls. ASE results in a reduced expression of the gene, is dominantly inherited, segregates in families, and occurs in sporadic CRC cases. Although subtle, the reduction in constitutive TGFBR1 expression alters SMAD-mediated TGF-beta signaling. Two major TGFBR1 haplotypes are predominant among ASE cases, which suggested ancestral mutations, but causative germline changes were not identified. Conservative estimates suggested that ASE confers a substantially increased risk of CRC (odds ratio, 8.7; 95% confidence interval, 2.6 to 29.1), but these estimates required confirmation and were predicted to show ethnic differences. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18703712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Loeys-Dietz Syndrome</em></strong></p><p>
|
|
<a href="#14" class="mim-tip-reference" title="Loeys, B. L., Chen, J., Neptune, E. R., Judge, D. P., Podowski, M., Holm, T., Meyers, J., Leitch, C. C., Katsanis, N., Sharifi, N., Xu, F. L., Myers, L. A., and 12 others. <strong>A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2.</strong> Nature Genet. 37: 275-281, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15731757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15731757</a>] [<a href="https://doi.org/10.1038/ng1511" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15731757">Loeys et al. (2005)</a> described 10 families with an aortic aneurysm syndrome characterized by hypertelorism, bifid uvula and/or cleft palate, and generalized arterial tortuosity with ascending aortic aneurysm and dissection (see LDS1, <a href="/entry/609192">609192</a>). This syndrome showed autosomal dominant inheritance and variable clinical expression. Other findings in multiple systems included craniosynostosis, structural brain abnormalities such as type I Chiari malformation (<a href="/entry/118420">118420</a>), mental retardation, congenital heart disease (patent ductus arteriosus, atrial septal defect), and aneurysms with dissection throughout the arterial tree. Heterozygous mutations were found in the TGFBR1 gene in 4 of the 10 families and in the TGFBR2 gene (<a href="/entry/190182">190182</a>) in 6. Tissues derived from affected individuals showed increased expression of both collagen (see <a href="/entry/120150">120150</a>) and connective tissue growth factor (CTGF; <a href="/entry/121009">121009</a>), as well as nuclear enrichment of phosphorylated SMAD2, indicative of increased TGF-beta signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15731757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Loeys, B. L., Schwarze, U., Holm, T., Callewaert, B. L., Thomas, G. H., Pannu, H., De Backer, J. F., Oswald, G. L., Symoens, S., Manouvrier, S., Roberts, A. E., Faravelli, F., and 9 others. <strong>Aneurysm syndromes caused by mutations in the TGF-beta receptor.</strong> New Eng. J. Med. 355: 788-798, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16928994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16928994</a>] [<a href="https://doi.org/10.1056/NEJMoa055695" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16928994">Loeys et al. (2006)</a> undertook the clinical and molecular characterization of the families of 40 probands presenting with typical manifestations of Loeys-Dietz syndrome (LDS1). In view of the phenotypic overlap between this syndrome and vascular Ehlers-Danlos syndrome (EDS; <a href="/entry/130050">130050</a>), they screened an additional cohort of 40 patients who had been diagnosed provisionally with vascular EDS but lacked the characteristic abnormalities of type III collagen (<a href="/entry/120180">120180</a>). Of these 40 probands, 4 carried a heterozygous mutation in TGFBR1 (3 of which involved codon 487; see, e.g., <a href="#0004">190181.0004</a> and <a href="#0007">190181.0007</a>) and were classified as having Loeys-Dietz syndrome-2, a phenotypic classification denoting absence of craniofacial involvement. Overall, 13 mutations were found in TGFBR1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16928994" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Ades, L. C., Sullivan, K., Biggin, A., Haan, E. A., Brett, M., Holman, K. J., Dixon, J., Robertson, S., Holmes, A. D., Rogers, J., Bennetts, B. <strong>FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited.</strong> Am. J. Med. Genet. 140A: 1047-1058, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16596670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16596670</a>] [<a href="https://doi.org/10.1002/ajmg.a.31202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16596670">Ades et al. (2006)</a> discussed the phenotypes and genotypes of 5 individuals with conditions within the Marfan syndrome/marfanoid-craniosynostosis/marfanoid-metal retardation spectrum in light of evidence of abnormal TGF-beta signaling in the pathogenesis of Marfan-like phenotypes. In 2 unrelated patients with Furlong syndrome (see <a href="/entry/609192">609192</a>) they described the same missense mutation in TGFBR1 (<a href="#0005">190181.0005</a>). The other 3 patients had alterations of the FBN1 gene (<a href="/entry/134797">134797</a>). <a href="#1" class="mim-tip-reference" title="Ades, L. C., Sullivan, K., Biggin, A., Haan, E. A., Brett, M., Holman, K. J., Dixon, J., Robertson, S., Holmes, A. D., Rogers, J., Bennetts, B. <strong>FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited.</strong> Am. J. Med. Genet. 140A: 1047-1058, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16596670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16596670</a>] [<a href="https://doi.org/10.1002/ajmg.a.31202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16596670">Ades et al. (2006)</a> concluded that their findings supported the notion that perturbation of extracellular matrix homeostasis and/or remodeling caused by abnormal TGF-beta signaling is the core pathogenetic mechanism in Marfan syndrome and related entities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16596670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In patients with phenotypes classified as type 2 Marfan syndrome, Loeys-Dietz syndrome, or thoracic aortic aneurysm with dissection (TAAD), <a href="#16" class="mim-tip-reference" title="Matyas, G., Arnold, E., Carrel, T., Baumgartner, D., Boileau, C., Berger, W., Steinmann, B. <strong>Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations in Marfan syndrome-related disorders.</strong> Hum. Mutat. 27: 760-769, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16791849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16791849</a>] [<a href="https://doi.org/10.1002/humu.20353" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16791849">Matyas et al. (2006)</a> detected 3 novel mutations in the TGFBR1 gene. A heterozygous arg487-to-gln (R487Q) mutation (<a href="#0006">190181.0006</a>) was present in a patient with TAAD; mutation of the same residue to pro (R487P; <a href="#0004">190181.0004</a>) had been previously reported in a family whose phenotype was identified as Loeys-Dietz syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16791849" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Singh, K. K., Rommel, K., Mishra, A., Karck, M., Haverich, A., Schmidtke, J., Arslan-Kirchner, M. <strong>TGFBR1 and TGFBR2 mutations in patients with features of Marfan syndrome and Loeys-Dietz syndrome.</strong> Hum. Mutat. 27: 770-777, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16799921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16799921</a>] [<a href="https://doi.org/10.1002/humu.20354" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16799921">Singh et al. (2006)</a> searched for TGFBR1 and TGFBR2 mutations in 41 unrelated patients fulfilling the diagnostic criteria of the Ghent nosology (<a href="#3" class="mim-tip-reference" title="De Paepe, A., Devereux, R. B., Dietz, H. C., Hennekam, R. C. M., Pyeritz, R. E. <strong>Revised diagnostic criteria for the Marfan syndrome.</strong> Am. J. Med. Genet. 62: 417-426, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8723076/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8723076</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960424)62:4<417::AID-AJMG15>3.0.CO;2-R" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8723076">De Paepe et al., 1996</a>) or with a tentative diagnosis of Marfan syndrome, in whom mutations in the FBN1 coding region were not identified. In TGFBR1, 2 mutations and 2 polymorphisms were detected. In TGFBR2, 5 mutations and 6 polymorphisms were identified. Reexamination of patients with a TGFBR1 or TGFBR2 mutation revealed extensive clinical overlap between these patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16799921+8723076" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Susceptibility To Multiple Self-Healing Squamous Epithelioma</em></strong></p><p>
|
|
In affected members of 18 different families with autosomal dominant multiple self-healing squamous epithelioma (MSSE; <a href="/entry/132800">132800</a>), <a href="#8" class="mim-tip-reference" title="Goudie, D. R., D'Alessandro, M., Merriman, B., Lee, H., Szeverenyi, I., Avery, S., O'Connor, B. D., Nelson, S. F., Coats, S. E., Stewart, A., Christie, L., Pichert, G., and 11 others. <strong>Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1.</strong> Nature Genet. 43: 365-369, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21358634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21358634</a>] [<a href="https://doi.org/10.1038/ng.780" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21358634">Goudie et al. (2011)</a> identified 11 different heterozygous mutations in the TGFBR1 gene (see, e.g., <a href="#0009">190181.0009</a>-<a href="#0012">190181.0012</a>). The phenotype is characterized by the development of multiple squamous carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before showing spontaneous regression, leaving scars. The mutations identified by <a href="#8" class="mim-tip-reference" title="Goudie, D. R., D'Alessandro, M., Merriman, B., Lee, H., Szeverenyi, I., Avery, S., O'Connor, B. D., Nelson, S. F., Coats, S. E., Stewart, A., Christie, L., Pichert, G., and 11 others. <strong>Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1.</strong> Nature Genet. 43: 365-369, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21358634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21358634</a>] [<a href="https://doi.org/10.1038/ng.780" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21358634">Goudie et al. (2011)</a> occurred in either the extracellular ligand-binding domain (exon 2) or in the serine/threonine kinase domain (exons 4, 6, and 7), and all were predicted or demonstrated to result in loss of receptor function. Several mutation carriers were unaffected, and tumor tissue from some patients showed loss of heterozygosity for the wildtype allele. Overall, the findings were consistent with wildtype TGFBR1 acting as a tumor suppressor, until somatic deletion by a classic second hit results in carcinogenesis. <a href="#8" class="mim-tip-reference" title="Goudie, D. R., D'Alessandro, M., Merriman, B., Lee, H., Szeverenyi, I., Avery, S., O'Connor, B. D., Nelson, S. F., Coats, S. E., Stewart, A., Christie, L., Pichert, G., and 11 others. <strong>Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1.</strong> Nature Genet. 43: 365-369, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21358634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21358634</a>] [<a href="https://doi.org/10.1038/ng.780" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21358634">Goudie et al. (2011)</a> noted that TGFBR1 mutations causing Loeys-Dietz syndrome result in activation of the TGFB1 signaling pathway, whereas TGFBR1 mutations causing MSSE result in loss of the TGFB1 signaling pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21358634" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Susceptibility To Abdominal Aortic Aneurysm</em></strong></p><p>
|
|
For discussion of a possible association between variation in the TGFBR1 gene and susceptibility to abdominal aortic aneurysm, see AAA (<a href="/entry/100070">100070</a>).</p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
For discussion of a possible association between variation near the TGFBR1 gene and age-related macular degeneration, see ARMD1 (<a href="/entry/603075">603075</a>).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>To better define the function of TGF-beta in hematopoiesis and angiogenesis, <a href="#13" class="mim-tip-reference" title="Larsson, J., Goumans, M.-J., Sjostrand, L. J., van Rooijen, M. A., Ward, D., Leveen, P., Xu, X., Dijke, P., Mummery, C. L., Karlsson, S. <strong>Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient mice.</strong> EMBO J. 20: 1663-1673, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11285230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11285230</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11285230[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/emboj/20.7.1663" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11285230">Larsson et al. (2001)</a> used gene targeting to inactivate the Tgfbr1 gene in mice. Mice lacking Tgfbr1 died at midgestation, exhibited severe defects in the vascular development of the yolk sac and placenta, and lacked circulating red blood cells. Analysis of yolk sac-derived hematopoietic precursors of Tgfbr1 null mice revealed normal hematopoietic potential. However, endothelial cells from these embryos showed enhanced cell proliferation, improper migratory behavior, and impaired fibronectin (<a href="/entry/135600">135600</a>) production in vitro. <a href="#13" class="mim-tip-reference" title="Larsson, J., Goumans, M.-J., Sjostrand, L. J., van Rooijen, M. A., Ward, D., Leveen, P., Xu, X., Dijke, P., Mummery, C. L., Karlsson, S. <strong>Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient mice.</strong> EMBO J. 20: 1663-1673, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11285230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11285230</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11285230[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/emboj/20.7.1663" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11285230">Larsson et al. (2001)</a> noted that these endothelial defects are associated with the vascular defects seen in vivo. They concluded that Tgfbr1-dependent signaling is required for angiogenesis, but not for the development of hematopoietic progenitor cells and functional hematopoiesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11285230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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/190181" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=190181[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 LOEYS-DIETZ SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TGFBR1, MET318ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121918710 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918710;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=rs121918710" 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=rs121918710" 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=RCV000119102" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000119102" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000119102</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with Loeys-Dietz syndrome (LDS1; <a href="/entry/609192">609192</a>), <a href="#14" class="mim-tip-reference" title="Loeys, B. L., Chen, J., Neptune, E. R., Judge, D. P., Podowski, M., Holm, T., Meyers, J., Leitch, C. C., Katsanis, N., Sharifi, N., Xu, F. L., Myers, L. A., and 12 others. <strong>A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2.</strong> Nature Genet. 37: 275-281, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15731757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15731757</a>] [<a href="https://doi.org/10.1038/ng1511" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15731757">Loeys et al. (2005)</a> found a 953T-G transversion on exon 5 of the TGFBR1 gene that resulted in a met318-to-arg (M318R) substitution in the kinase domain of the protein. The mutation occurred de novo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15731757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 LOEYS-DIETZ SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TGFBR1, ASP400GLY
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121918711 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918711;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=rs121918711" 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=rs121918711" 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=RCV000013346" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013346" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013346</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with Loeys-Dietz syndrome (LDS1; <a href="/entry/609192">609192</a>), <a href="#14" class="mim-tip-reference" title="Loeys, B. L., Chen, J., Neptune, E. R., Judge, D. P., Podowski, M., Holm, T., Meyers, J., Leitch, C. C., Katsanis, N., Sharifi, N., Xu, F. L., Myers, L. A., and 12 others. <strong>A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2.</strong> Nature Genet. 37: 275-281, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15731757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15731757</a>] [<a href="https://doi.org/10.1038/ng1511" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15731757">Loeys et al. (2005)</a> identified an 1199A-G transition in exon 7 of the TGFBR1 gene, resulting in an asp400-to-gly (D400G) substitution in the kinase domain of the protein. The mutation occurred de novo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15731757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 LOEYS-DIETZ SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TGFBR1, THR200ILE
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121918712 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918712;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=rs121918712" 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=rs121918712" 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=RCV000013347" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013347" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013347</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with Loeys-Dietz syndrome (LDS1; <a href="/entry/609192">609192</a>), <a href="#14" class="mim-tip-reference" title="Loeys, B. L., Chen, J., Neptune, E. R., Judge, D. P., Podowski, M., Holm, T., Meyers, J., Leitch, C. C., Katsanis, N., Sharifi, N., Xu, F. L., Myers, L. A., and 12 others. <strong>A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2.</strong> Nature Genet. 37: 275-281, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15731757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15731757</a>] [<a href="https://doi.org/10.1038/ng1511" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15731757">Loeys et al. (2005)</a> identified a 599C-T transition in exon 4 of the TGFBR1 gene that resulted in a thr200-to-ile (T200I) substitution at the junction of the glycine-serine-rich domain and the kinase domain of the TGFBR1 protein. The mutation occurred de novo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15731757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 LOEYS-DIETZ SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TGFBR1, ARG487PRO
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs113605875 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs113605875;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=rs113605875" 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=rs113605875" 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=RCV000013348" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013348" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013348</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with Loeys-Dietz syndrome (LDS1; <a href="/entry/609192">609192</a>), <a href="#14" class="mim-tip-reference" title="Loeys, B. L., Chen, J., Neptune, E. R., Judge, D. P., Podowski, M., Holm, T., Meyers, J., Leitch, C. C., Katsanis, N., Sharifi, N., Xu, F. L., Myers, L. A., and 12 others. <strong>A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2.</strong> Nature Genet. 37: 275-281, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15731757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15731757</a>] [<a href="https://doi.org/10.1038/ng1511" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15731757">Loeys et al. (2005)</a> found a 1460G-C transversion in exon 9 of the TGFBR1 gene that resulted in an arg487-to-pro (R487P) amino acid substitution. The R487P mutation segregated with the disorder in a father and 2 sons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15731757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Loeys, B. L., Schwarze, U., Holm, T., Callewaert, B. L., Thomas, G. H., Pannu, H., De Backer, J. F., Oswald, G. L., Symoens, S., Manouvrier, S., Roberts, A. E., Faravelli, F., and 9 others. <strong>Aneurysm syndromes caused by mutations in the TGF-beta receptor.</strong> New Eng. J. Med. 355: 788-798, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16928994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16928994</a>] [<a href="https://doi.org/10.1056/NEJMoa055695" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16928994">Loeys et al. (2006)</a> classified LDS in the family reported by <a href="#14" class="mim-tip-reference" title="Loeys, B. L., Chen, J., Neptune, E. R., Judge, D. P., Podowski, M., Holm, T., Meyers, J., Leitch, C. C., Katsanis, N., Sharifi, N., Xu, F. L., Myers, L. A., and 12 others. <strong>A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2.</strong> Nature Genet. 37: 275-281, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15731757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15731757</a>] [<a href="https://doi.org/10.1038/ng1511" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15731757">Loeys et al. (2005)</a> as LDS1 on the basis of craniofacial findings, but found the same mutation in another patient with LDS classified as LDS2 (lacking typical craniofacial findings). Other missense mutations involving the same codon, R487Q (<a href="#0007">190181.0007</a>) and R487W (<a href="#0007">190181.0007</a>), have been identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16928994+15731757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 LOEYS-DIETZ SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TGFBR1, SER241LEU
|
|
</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> rs111854391 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111854391;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/rs111854391?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=rs111854391" 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=rs111854391" 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=RCV000013350 OR RCV000030540 OR RCV000244262 OR RCV000442105 OR RCV000617152 OR RCV000845292 OR RCV003224094" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013350, RCV000030540, RCV000244262, RCV000442105, RCV000617152, RCV000845292, RCV003224094" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013350...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 patients judged to have Furlong syndrome (see LDS1, <a href="/entry/609192">609192</a>), <a href="#1" class="mim-tip-reference" title="Ades, L. C., Sullivan, K., Biggin, A., Haan, E. A., Brett, M., Holman, K. J., Dixon, J., Robertson, S., Holmes, A. D., Rogers, J., Bennetts, B. <strong>FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited.</strong> Am. J. Med. Genet. 140A: 1047-1058, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16596670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16596670</a>] [<a href="https://doi.org/10.1002/ajmg.a.31202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16596670">Ades et al. (2006)</a> found an identical heterozygous missense mutation, ser241 to leu (S241L), in the TGFBR1 gene. The mutation, which arose from a C-to-T transition at nucleotide position 722, alters a highly conserved nonpolar serine in the serine-threonine kinase domain to a polar leucine residue. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16596670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 LOEYS-DIETZ SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TGFBR1, ARG487GLN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs113605875 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs113605875;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=rs113605875" 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=rs113605875" 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=RCV000013351 OR RCV000196834 OR RCV000211857 OR RCV000463090 OR RCV001194075 OR RCV004730845" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013351, RCV000196834, RCV000211857, RCV000463090, RCV001194075, RCV004730845" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013351...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 43-year-old patient with thoracic aortic aneurysm and dissection (see <a href="/entry/609192">609192</a>), <a href="#16" class="mim-tip-reference" title="Matyas, G., Arnold, E., Carrel, T., Baumgartner, D., Boileau, C., Berger, W., Steinmann, B. <strong>Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations in Marfan syndrome-related disorders.</strong> Hum. Mutat. 27: 760-769, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16791849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16791849</a>] [<a href="https://doi.org/10.1002/humu.20353" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16791849">Matyas et al. (2006)</a> found a de novo heterozygous 1460G-A transition in exon 9 of the TGFBR1 gene that caused an arg487-to-gln substitution in the protein (R487Q). Mutation at this codon had been found previously (<a href="#0004">190181.0004</a>). The mutation occurred in the kinase domain of the protein and was predicted to affect protein function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16791849" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 LOEYS-DIETZ SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TGFBR1, ARG487TRP
|
|
</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> rs111426349 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111426349;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/rs111426349?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=rs111426349" 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=rs111426349" 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=RCV000013352 OR RCV000200764 OR RCV000211856 OR RCV000251089 OR RCV000763611 OR RCV004802936" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013352, RCV000200764, RCV000211856, RCV000251089, RCV000763611, RCV004802936" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013352...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a woman with Loeys-Dietz syndrome without typical craniofacial findings (LDS1; <a href="/entry/609192">609192</a>), <a href="#15" class="mim-tip-reference" title="Loeys, B. L., Schwarze, U., Holm, T., Callewaert, B. L., Thomas, G. H., Pannu, H., De Backer, J. F., Oswald, G. L., Symoens, S., Manouvrier, S., Roberts, A. E., Faravelli, F., and 9 others. <strong>Aneurysm syndromes caused by mutations in the TGF-beta receptor.</strong> New Eng. J. Med. 355: 788-798, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16928994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16928994</a>] [<a href="https://doi.org/10.1056/NEJMoa055695" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16928994">Loeys et al. (2006)</a> found an arg487-to-trp (R487W) missense mutation in the TGFBR1 gene. The patient had aortic root aneurysm with dissection, other arterial aneurysm, arterial tortuosity, vascular rupture during pregnancy, uterine hemorrhage, bowel rupture, inguinal hernia, velvety skin, skin hyperextensibility, atrophic scars, and joint laxity. Another missense mutation at the same codon had been described (R487P; <a href="#0004">190181.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16928994" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 11 affected members of a 4-generation family with thoracic aortic aneurysm as well as aneurysms and dissections of other arteries, originally reported by <a href="#17" class="mim-tip-reference" title="Nicod, P., Bloor, C., Godfrey, M., Hollister, D., Pyeritz, R. E., Dittrich, H., Polikar, R., Peterson, K. L. <strong>Familial aortic dissecting aneurysm.</strong> J. Am. Coll. Cardiol. 13: 811-819, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2647812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2647812</a>] [<a href="https://doi.org/10.1016/0735-1097(89)90221-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2647812">Nicod et al. (1989)</a>, <a href="#20" class="mim-tip-reference" title="Tran-Fadulu, V., Pannu, H., Kim, D. H., Vick, G. W., III, Lonsford, C. M., Lafont, A. L., Boccalandro, C., Smart, S., Peterson, K. L., Hain, J. Z., Willing, M. C., Coselli, J. S., LeMaire, S. A., Ahn, C., Byers, P. H., Milewicz, D. M. <strong>Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations.</strong> J. Med. Genet. 46: 607-613, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19542084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19542084</a>] [<a href="https://doi.org/10.1136/jmg.2008.062844" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19542084">Tran-Fadulu et al. (2009)</a> identified heterozygosity for the R487W mutation in the TGFBR1 gene. Imaging of the cerebrovascular circulation in 2 affected family members showed tortuous vessels and fusiform dilation of the basilar artery. <a href="#20" class="mim-tip-reference" title="Tran-Fadulu, V., Pannu, H., Kim, D. H., Vick, G. W., III, Lonsford, C. M., Lafont, A. L., Boccalandro, C., Smart, S., Peterson, K. L., Hain, J. Z., Willing, M. C., Coselli, J. S., LeMaire, S. A., Ahn, C., Byers, P. H., Milewicz, D. M. <strong>Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations.</strong> J. Med. Genet. 46: 607-613, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19542084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19542084</a>] [<a href="https://doi.org/10.1136/jmg.2008.062844" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19542084">Tran-Fadulu et al. (2009)</a> stated that examination of 6 family members revealed no features of Loeys-Dietz syndrome type 1; specifically, none had bifid uvula, craniosynostosis, hypertelorism, or translucent skin. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19542084+2647812" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 LOEYS-DIETZ SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TGFBR1, GLY174VAL
|
|
</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> rs121918713 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918713;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/rs121918713?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=rs121918713" 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=rs121918713" 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=RCV000013353 OR RCV005054137" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013353, RCV005054137" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013353...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 45-year-old Italian man with Loeys-Dietz syndrome (LDS1; <a href="/entry/609192">609192</a>), <a href="#4" class="mim-tip-reference" title="Drera, B., Tadini, G., Barlati, S., Colombi, M. <strong>Identification of a novel TGFBR1 mutation in a Loeys-Dietz syndrome type II patient with vascular Ehlers-Danlos syndrome phenotype. (Letter)</strong> Clin. Genet. 73: 290-293, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18070134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18070134</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00942.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18070134">Drera et al. (2008)</a> identified a heterozygous 521G-T transversion in exon 3 of the TGFBR1 gene, resulting in a gly174-to-val (G174V) substitution in the intracellular region of the receptor. The mutation was not identified in 200 chromosomes from Italian controls nor in the patient's unaffected daughter. The patient had a prominent and narrow nose, thin lips, bifid uvula and cleft palate, hypermobility of small joints, and soft skin. He also had a history of dissection of both internal iliac arteries and the right femoral artery. There was no aortic root dilatation or tortuosity of the great vessels. The patient had been classified phenotypically as type 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18070134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MULTIPLE SELF-HEALING SQUAMOUS EPITHELIOMA, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TGFBR1, ASN45SER
|
|
</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> rs387906696 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906696;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/rs387906696?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=rs387906696" 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=rs387906696" 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=RCV000022802 OR RCV000454530 OR RCV000654793 OR RCV000766900 OR RCV001374784 OR RCV002477006 OR RCV003996113" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022802, RCV000454530, RCV000654793, RCV000766900, RCV001374784, RCV002477006, RCV003996113" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022802...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 symptomatic members of a Scottish family with autosomal dominant multiple self-healing squamous epithelioma (MSSE; <a href="/entry/132800">132800</a>), <a href="#8" class="mim-tip-reference" title="Goudie, D. R., D'Alessandro, M., Merriman, B., Lee, H., Szeverenyi, I., Avery, S., O'Connor, B. D., Nelson, S. F., Coats, S. E., Stewart, A., Christie, L., Pichert, G., and 11 others. <strong>Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1.</strong> Nature Genet. 43: 365-369, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21358634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21358634</a>] [<a href="https://doi.org/10.1038/ng.780" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21358634">Goudie et al. (2011)</a> identified a heterozygous 134A-G transition in exon 2 of the TGFBR1 gene, resulting in an asn45-to-ser (N45S) substitution in the extracellular ligand-binding domain. One additional asymptomatic family member also carried the mutation, which was not found in 80 Scottish controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21358634" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MULTIPLE SELF-HEALING SQUAMOUS EPITHELIOMA, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TGFBR1, GLY52ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776865 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776865;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=rs587776865" 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=rs587776865" 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=RCV000022803 OR RCV000777702" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022803, RCV000777702" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022803...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected individuals from 7 Scottish families with autosomal dominant multiple self-healing squamous epithelioma (MSSE; <a href="/entry/132800">132800</a>), previously reported by <a href="#6" class="mim-tip-reference" title="Ferguson-Smith, M. A., Wallace, D. C., James, Z. H., Renwick, J. H. <strong>Multiple self-healing squamous epithelioma.</strong> Birth Defects Orig. Art. Ser. VII(8): 157-163, 1971.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5173258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5173258</a>]" pmid="5173258">Ferguson-Smith et al., 1971</a> and <a href="#9" class="mim-tip-reference" title="Goudie, D. R., Yuille, M. A. R., Leversha, M. A., Furlong, R. A., Carter, N. P., Lush, M. J., Affara, N. A., Ferguson-Smith, M. A. <strong>Multiple self-healing squamous epitheliomata (ESS1) mapped to chromosome 9q22-q31 in families with common ancestry.</strong> Nature Genet. 3: 165-169, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499949</a>] [<a href="https://doi.org/10.1038/ng0293-165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8499949">Goudie et al., 1993</a>, <a href="#8" class="mim-tip-reference" title="Goudie, D. R., D'Alessandro, M., Merriman, B., Lee, H., Szeverenyi, I., Avery, S., O'Connor, B. D., Nelson, S. F., Coats, S. E., Stewart, A., Christie, L., Pichert, G., and 11 others. <strong>Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1.</strong> Nature Genet. 43: 365-369, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21358634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21358634</a>] [<a href="https://doi.org/10.1038/ng.780" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21358634">Goudie et al. (2011)</a> identified a heterozygous 154G-C transversion in exon 2 of the TGFBR1 gene, resulting in a gly52-to-arg (G52R) substitution in the extracellular ligand-binding domain. Asymptomatic family members in several families also carried the mutation, which was not found in 80 Scottish controls. Studies of tumor tissue from an affected individual showed that the mutant protein was expressed and localized to the plasma membrane, but there was some loss of heterozygosity for the wildtype allele. SMAD reporter assay showed that the mutant G52R receptor protein gave lower activation than the wildtype protein in response to TGFB1 stimulation, consistent with a loss of function. Overall, the findings were consistent with wildtype TGFBR1 acting as a tumor suppressor, until somatic deletion by a classic second hit results in carcinogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8499949+21358634+5173258" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MULTIPLE SELF-HEALING SQUAMOUS EPITHELIOMA, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TGFBR1, IVS4AS, A-C, -2
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776866 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776866;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=rs587776866" 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=rs587776866" 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=RCV000022804 OR RCV004802947" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022804, RCV004802947" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022804...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 affected individuals from an English family with autosomal dominant multiple self-healing squamous epithelioma (MSSE; <a href="/entry/132800">132800</a>), <a href="#8" class="mim-tip-reference" title="Goudie, D. R., D'Alessandro, M., Merriman, B., Lee, H., Szeverenyi, I., Avery, S., O'Connor, B. D., Nelson, S. F., Coats, S. E., Stewart, A., Christie, L., Pichert, G., and 11 others. <strong>Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1.</strong> Nature Genet. 43: 365-369, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21358634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21358634</a>] [<a href="https://doi.org/10.1038/ng.780" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21358634">Goudie et al. (2011)</a> identified a heterozygous A-to-C transversion (806-2A-C) in intron 4 of the TGFBR1 gene, resulting in a splice site mutation in a region containing the serine/threonine kinase domain. The mutation was predicted to result in loss of receptor signaling. The mutation was not found in 80 Scottish controls. Tumor tissue from an affected individual showed loss of heterozygosity for the wildtype allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21358634" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 MULTIPLE SELF-HEALING SQUAMOUS EPITHELIOMA, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
TGFBR1, ARG414TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906697 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906697;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=rs387906697" 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=rs387906697" 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=RCV000022805 OR RCV000474057" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022805, RCV000474057" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022805...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 affected individuals from an English family with autosomal dominant multiple self-healing squamous epithelioma (MSSE; <a href="/entry/132800">132800</a>), <a href="#8" class="mim-tip-reference" title="Goudie, D. R., D'Alessandro, M., Merriman, B., Lee, H., Szeverenyi, I., Avery, S., O'Connor, B. D., Nelson, S. F., Coats, S. E., Stewart, A., Christie, L., Pichert, G., and 11 others. <strong>Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1.</strong> Nature Genet. 43: 365-369, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21358634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21358634</a>] [<a href="https://doi.org/10.1038/ng.780" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21358634">Goudie et al. (2011)</a> identified a heterozygous 1240C-T transition in exon 7 of the TGFBR1 gene, resulting in an arg414-to-ter (R414X) substitution in the serine/threonine kinase domain. The mutation resulted in nonsense-mediated mRNA decay, causing a loss of receptor signaling. The mutation was not found in 80 Scottish controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21358634" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Ades2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ades, L. C., Sullivan, K., Biggin, A., Haan, E. A., Brett, M., Holman, K. J., Dixon, J., Robertson, S., Holmes, A. D., Rogers, J., Bennetts, B.
|
|
<strong>FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited.</strong>
|
|
Am. J. Med. Genet. 140A: 1047-1058, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16596670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16596670</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16596670" 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.31202" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Barrios-Rodiles2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Barrios-Rodiles, M., Brown, K. R., Ozdamar, B., Bose, R., Liu, Z., Donovan, R. S., Shinjo, F., Liu, Y., Dembowy, J., Taylor, I. W., Luga, V., Przulj, N., Robinson, M., Suzuki, H., Hayashizaki, Y., Jurisica, I., Wrana, J. L.
|
|
<strong>High-throughput mapping of a dynamic signaling network in mammalian cells.</strong>
|
|
Science 307: 1621-1625, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15761153/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15761153</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15761153" 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.1105776" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="De Paepe1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
De Paepe, A., Devereux, R. B., Dietz, H. C., Hennekam, R. C. M., Pyeritz, R. E.
|
|
<strong>Revised diagnostic criteria for the Marfan syndrome.</strong>
|
|
Am. J. Med. Genet. 62: 417-426, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8723076/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8723076</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8723076" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1096-8628(19960424)62:4<417::AID-AJMG15>3.0.CO;2-R" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Drera2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Drera, B., Tadini, G., Barlati, S., Colombi, M.
|
|
<strong>Identification of a novel TGFBR1 mutation in a Loeys-Dietz syndrome type II patient with vascular Ehlers-Danlos syndrome phenotype. (Letter)</strong>
|
|
Clin. Genet. 73: 290-293, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18070134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18070134</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18070134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2007.00942.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Ebner1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ebner, R., Chen, R.-H., Shum, L., Lawler, S., Zioncheck, T. F., Lee, A., Lopez, A. R., Derynck, R.
|
|
<strong>Cloning of a type I TGF-beta receptor and its effect on TGF-beta binding to the type II receptor.</strong>
|
|
Science 260: 1344-1348, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8388127/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8388127</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8388127" 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.8388127" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Ferguson-Smith1971" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ferguson-Smith, M. A., Wallace, D. C., James, Z. H., Renwick, J. H.
|
|
<strong>Multiple self-healing squamous epithelioma.</strong>
|
|
Birth Defects Orig. Art. Ser. VII(8): 157-163, 1971.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5173258/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5173258</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5173258" 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="7" class="mim-anchor"></a>
|
|
<a id="Franzen1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Franzen, P., ten Dijke, P., Ichijo, H., Yamashita, H., Schulz, P., Heldin, C.-H., Miyazono, K.
|
|
<strong>Cloning of a TGF-beta type I receptor that forms a heteromeric complex with the TGF-beta type II receptor.</strong>
|
|
Cell 75: 681-692, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8242743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8242743</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8242743" 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(93)90489-d" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Goudie2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goudie, D. R., D'Alessandro, M., Merriman, B., Lee, H., Szeverenyi, I., Avery, S., O'Connor, B. D., Nelson, S. F., Coats, S. E., Stewart, A., Christie, L., Pichert, G., and 11 others.
|
|
<strong>Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1.</strong>
|
|
Nature Genet. 43: 365-369, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21358634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21358634</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21358634" 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.780" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Goudie1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goudie, D. R., Yuille, M. A. R., Leversha, M. A., Furlong, R. A., Carter, N. P., Lush, M. J., Affara, N. A., Ferguson-Smith, M. A.
|
|
<strong>Multiple self-healing squamous epitheliomata (ESS1) mapped to chromosome 9q22-q31 in families with common ancestry.</strong>
|
|
Nature Genet. 3: 165-169, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8499949/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8499949</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8499949" 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/ng0293-165" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Inman2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Inman, G. J., Nicolas, F. J., Hill, C. S.
|
|
<strong>Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-beta receptor activity.</strong>
|
|
Molec. Cell 10: 283-294, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12191474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12191474</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12191474" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s1097-2765(02)00585-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Johnson1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johnson, D. W., Qumsiyeh, M., Benkhalifa, M., Marchuk, D. A.
|
|
<strong>Assignment of human transforming growth factor-beta type I and type III receptor genes (TGFBR1 and TGFBR3) to 9q33-q34 and 1p32-p33, respectively.</strong>
|
|
Genomics 28: 356-357, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8530052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8530052</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8530052" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1995.1157" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Kuan1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kuan, J., Kono, D. H.
|
|
<strong>Tgfbr1 maps to chromosome 4.</strong>
|
|
Mammalian Genome 9: 95-96, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9434964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9434964</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9434964" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s003359900695" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Larsson2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Larsson, J., Goumans, M.-J., Sjostrand, L. J., van Rooijen, M. A., Ward, D., Leveen, P., Xu, X., Dijke, P., Mummery, C. L., Karlsson, S.
|
|
<strong>Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient mice.</strong>
|
|
EMBO J. 20: 1663-1673, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11285230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11285230</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11285230[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=11285230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/emboj/20.7.1663" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Loeys2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Loeys, B. L., Chen, J., Neptune, E. R., Judge, D. P., Podowski, M., Holm, T., Meyers, J., Leitch, C. C., Katsanis, N., Sharifi, N., Xu, F. L., Myers, L. A., and 12 others.
|
|
<strong>A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2.</strong>
|
|
Nature Genet. 37: 275-281, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15731757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15731757</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15731757" 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/ng1511" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Loeys2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Loeys, B. L., Schwarze, U., Holm, T., Callewaert, B. L., Thomas, G. H., Pannu, H., De Backer, J. F., Oswald, G. L., Symoens, S., Manouvrier, S., Roberts, A. E., Faravelli, F., and 9 others.
|
|
<strong>Aneurysm syndromes caused by mutations in the TGF-beta receptor.</strong>
|
|
New Eng. J. Med. 355: 788-798, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16928994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16928994</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16928994" 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/NEJMoa055695" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Matyas2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matyas, G., Arnold, E., Carrel, T., Baumgartner, D., Boileau, C., Berger, W., Steinmann, B.
|
|
<strong>Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations in Marfan syndrome-related disorders.</strong>
|
|
Hum. Mutat. 27: 760-769, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16791849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16791849</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16791849" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.20353" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Nicod1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nicod, P., Bloor, C., Godfrey, M., Hollister, D., Pyeritz, R. E., Dittrich, H., Polikar, R., Peterson, K. L.
|
|
<strong>Familial aortic dissecting aneurysm.</strong>
|
|
J. Am. Coll. Cardiol. 13: 811-819, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2647812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2647812</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2647812" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0735-1097(89)90221-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Pasche1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pasche, B., Luo, Y., Rao, P. H., Nimer, S. D., Dmitrovsky, E., Caron, P., Luzzatto, L., Offit, K., Cordon-Cardo, C., Renault, B., Satagopan, J. M., Murty, V. V., Massague, J.
|
|
<strong>Type I transforming growth factor beta receptor maps to 9q22 and exhibits a polymorphism and a rare variant within a polyalanine tract.</strong>
|
|
Cancer Res. 58: 2727-2732, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9661882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9661882</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9661882" 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="19" class="mim-anchor"></a>
|
|
<a id="Singh2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Singh, K. K., Rommel, K., Mishra, A., Karck, M., Haverich, A., Schmidtke, J., Arslan-Kirchner, M.
|
|
<strong>TGFBR1 and TGFBR2 mutations in patients with features of Marfan syndrome and Loeys-Dietz syndrome.</strong>
|
|
Hum. Mutat. 27: 770-777, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16799921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16799921</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16799921" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.20354" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Tran-Fadulu2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tran-Fadulu, V., Pannu, H., Kim, D. H., Vick, G. W., III, Lonsford, C. M., Lafont, A. L., Boccalandro, C., Smart, S., Peterson, K. L., Hain, J. Z., Willing, M. C., Coselli, J. S., LeMaire, S. A., Ahn, C., Byers, P. H., Milewicz, D. M.
|
|
<strong>Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations.</strong>
|
|
J. Med. Genet. 46: 607-613, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19542084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19542084</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19542084" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2008.062844" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Valle2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Valle, L., Serena-Acedo, T., Liyanarachchi, S., Hampel, H., Comeras, I., Li, Z., Zeng, Q., Zhang, H.-T., Pennison, M. J., Sadim, M., Pasche, B., Tanner, S. M., de la Chapelle, A.
|
|
<strong>Germline allele-specific expression of TGFBR1 confers an increased risk of colorectal cancer.</strong>
|
|
Science 321: 1361-1365, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18703712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18703712</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18703712[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=18703712" 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.1159397" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Vellucci1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vellucci, V. F., Reiss, M.
|
|
<strong>Cloning and genomic organization of the human transforming growth factor-beta type I receptor gene.</strong>
|
|
Genomics 46: 278-283, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9417915/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9417915</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9417915" 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.1997.5023" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Wang1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, T., Donahoe, P. K., Zervos, A. S.
|
|
<strong>Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12.</strong>
|
|
Science 265: 674-676, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7518616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7518616</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7518616" 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.7518616" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 4/22/2011
|
|
</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">
|
|
Marla J. F. O'Neill - updated : 1/28/2010<br>Ada Hamosh - updated : 10/1/2008<br>Cassandra L. Kniffin - updated : 5/6/2008<br>Victor A. McKusick - updated : 9/20/2006<br>Victor A. McKusick - updated : 8/24/2006<br>Victor A. McKusick - updated : 6/5/2006<br>Ada Hamosh - updated : 6/1/2005<br>Victor A. McKusick - updated : 2/4/2005<br>Patricia A. Hartz - updated : 12/16/2002<br>Stylianos E. Antonarakis - updated : 9/11/2002<br>Paul J. Converse - updated : 7/17/2000<br>Carol A. Bocchini - updated : 11/30/1999<br>Victor A. McKusick - updated : 2/19/1998<br>Victor A. McKusick - updated : 2/4/1998
|
|
</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 : 6/10/1993
|
|
</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">
|
|
alopez : 06/29/2021
|
|
</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 : 09/28/2018<br>carol : 12/15/2014<br>alopez : 4/22/2014<br>alopez : 4/7/2014<br>alopez : 1/11/2012<br>wwang : 4/25/2011<br>ckniffin : 4/22/2011<br>wwang : 2/2/2010<br>terry : 1/28/2010<br>alopez : 10/3/2008<br>alopez : 10/3/2008<br>terry : 10/1/2008<br>wwang : 5/13/2008<br>ckniffin : 5/6/2008<br>alopez : 3/31/2008<br>alopez : 3/7/2008<br>alopez : 10/11/2006<br>terry : 9/20/2006<br>alopez : 9/7/2006<br>alopez : 9/5/2006<br>terry : 8/24/2006<br>alopez : 6/8/2006<br>terry : 6/5/2006<br>carol : 1/18/2006<br>wwang : 6/2/2005<br>wwang : 6/1/2005<br>terry : 6/1/2005<br>alopez : 3/2/2005<br>alopez : 2/7/2005<br>terry : 2/4/2005<br>mgross : 12/18/2002<br>terry : 12/16/2002<br>mgross : 9/11/2002<br>mgross : 7/17/2000<br>carol : 12/1/1999<br>carol : 12/1/1999<br>carol : 11/30/1999<br>carol : 11/30/1999<br>alopez : 11/3/1998<br>dkim : 9/11/1998<br>terry : 2/19/1998<br>mark : 2/5/1998<br>terry : 2/4/1998<br>mark : 8/25/1995<br>carol : 9/30/1994<br>carol : 6/10/1993
|
|
</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> 190181
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
TRANSFORMING GROWTH FACTOR-BETA RECEPTOR, TYPE I; TGFBR1
|
|
|
|
</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">
|
|
ACTIVIN RECEPTOR-LIKE KINASE 5; ALK5
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: TGFBR1</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 9q22.33
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 9:99,103,647-99,154,192 </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="2">
|
|
<span class="mim-font">
|
|
9q22.33
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
{Multiple self-healing squamous epithelioma, susceptibility to}
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
132800
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Loeys-Dietz syndrome 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
609192
|
|
</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 TGFBR1 gene encodes a serine/threonine kinase receptor for transforming growth factor-beta (TGFB1; 190180). Most growth factor receptors are transmembrane tyrosine kinases or are associated with cytoplasmic tyrosine kinases. Another class of transmembrane receptors, however, is predicted to function as serine/threonine kinases. On the basis of their various biologic activities, different species of TGF-beta are probably potent developmental regulators of cell proliferation and differentiation. Several types of TGF-beta-binding proteins have been detected at the cell surface. Type I and type II receptors are defined on the basis of the mobility of their (125)I-TGF-beta cross-linked products in denaturing gels. These receptors probably mediate most activities of TGF-beta. The type II receptor (TGFBR2; 190182) functions as a transmembrane serine/threonine kinase and is required for the antiproliferative activity of TGF-beta, whereas the type I receptor mediates the induction of several genes involved in cell-matrix interactions (summary by Ebner et al., 1993). </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>Ebner et al. (1993) cloned a murine serine/threonine kinase receptor that shares a conserved extracellular domain with the type II TGF-beta receptor. Overexpression of this receptor alone did not increase cell surface binding of TGF-beta, but coexpression with the type II TGF-beta receptor caused TGF-beta to bind to this receptor, which had the size of the type I TGF-beta receptor. Overexpression of this newly cloned receptor inhibited binding of TGF-beta to the type II receptor in a dominant-negative fashion. Combinatorial interactions and stoichiometric ratios between the type I and II receptors may therefore determine the extent of TGF-beta binding and the resulting biologic activities. </p><p>By PCR analysis on human erythroleukemia cell cDNA using degenerate primers based on conserved regions of ser/thr kinase receptors, Franzen et al. (1993) isolated a cDNA encoding TGFBR1, which they called ALK5 (activin receptor-like kinase-5). The deduced 503-amino acid, 53-kD TGFBR1 ser/thr kinase contains a signal peptide; an extracellular cysteine-rich region with a single N-glycosylation site; a transmembrane region; and a putative cytoplasmic protein kinase domain. SDS-PAGE analysis showed that immunoprecipitation of TGFBR1 incubated with labeled TGFB1 produced a 70-kD complex as well as a heteromeric 94-kD TGFBR2 complex. Northern blot analysis detected a 5.5-kb TGFBR1 transcript in all tissues tested, with highest expression in placenta and lowest expression in brain and heart. Transient expression of TGFBR1 in a receptor-negative cell line led to the production of plasminogen activator inhibitor-1 (PAI1; 173360) in response to stimulation with TGFB1. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>TGFB1 regulates cell cycle progression by a unique signaling mechanism that involves its binding to TGFBR2 and activation of TGFBR1. Both are transmembrane serine/threonine receptor kinases. The TGFBR1 receptor may be inactivated in many of the cases of human tumor cells refractory to TGFB-mediated cell cycle arrest. Vellucci and Reiss (1997) reported that the TGFBR1 gene is approximately 31 kb long and contains 9 exons. The organization of the segment of the gene that encodes the C-terminal portion of the serine/threonine kinase domain appears to be highly conserved among members of the gene family. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Johnson et al. (1995) used PCR with a hybrid cell DNA panel and FISH to localize the TGFBR1 gene to chromosome 9q33-q34. By FISH, Pasche et al. (1998) localized the gene to chromosome 9q22. Kuan and Kono (1998) mapped the Tgfbr1 gene to mouse chromosome 4. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Wang et al. (1994) reported that the type I receptor may be a natural ligand for immunophilin FKBP12 (186945). </p><p>The membrane-bound protein encoded by TGFBR1 binds TGF-beta and forms a heterodimeric complex with the TGF-beta II receptor (Franzen et al., 1993; Johnson et al., 1995). Ligand binding by TGF-beta I receptors is dependent on coexpression with type II receptors. Type II receptors alone can bind ligand, but require association with type I receptors for activation of their kinase (signaling) function. </p><p>TGFB stimulation leads to phosphorylation and activation of SMAD2 (601366) and SMAD3 (603109), which form complexes with SMAD4 (600993) that accumulate in the nucleus and regulate transcription of target genes. Inman et al. (2002) demonstrated that following TGFB stimulation of epithelial cells, receptors remain active for at least 3 to 4 hours, and continuous receptor activity is required to maintain active SMADs in the nucleus and for TGFB-induced transcription. Continuous nucleocytoplasmic shuttling of the SMADs during active TGFB signaling provides the mechanism whereby the intracellular transducers of the signal continuously monitor receptor activity. These data explain how, at all times, the concentration of active SMADs in the nucleus is directly dictated by the levels of activated receptors in the cytoplasm. </p><p>Barrios-Rodiles et al. (2005) developed LUMIER (luminescence-based mammalian interactome mapping), an automated high-throughput technology, to map protein-protein interaction networks systematically in mammalian cells and applied it to the TGFB pathway. Analysis using self-organizing maps and k-means clustering identified links of the TGF-beta pathway to the p21-activated kinase (PAK; see 602590) network, to the polarity complex, and to occludin (602876), a structural component of tight junctions. Barrios-Rodiles et al. (2005) showed the occludin regulates TGFBR1 localization for efficient TGF-beta-dependent dissolution of tight junctions during epithelial-mesenchymal transitions. </p><p>Studying a Caucasian-dominated population in the U.S., Valle et al. (2008) showed that germline allele-specific expression (ASE) of the TGFBR1 gene is a quantitative trait that occurs in 10 to 20% of CRC patients and 1 to 3% of controls. ASE results in a reduced expression of the gene, is dominantly inherited, segregates in families, and occurs in sporadic CRC cases. Although subtle, the reduction in constitutive TGFBR1 expression alters SMAD-mediated TGF-beta signaling. Two major TGFBR1 haplotypes are predominant among ASE cases, which suggested ancestral mutations, but causative germline changes were not identified. Conservative estimates suggested that ASE confers a substantially increased risk of CRC (odds ratio, 8.7; 95% confidence interval, 2.6 to 29.1), but these estimates required confirmation and were predicted to show ethnic differences. </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>Loeys-Dietz Syndrome</em></strong></p><p>
|
|
Loeys et al. (2005) described 10 families with an aortic aneurysm syndrome characterized by hypertelorism, bifid uvula and/or cleft palate, and generalized arterial tortuosity with ascending aortic aneurysm and dissection (see LDS1, 609192). This syndrome showed autosomal dominant inheritance and variable clinical expression. Other findings in multiple systems included craniosynostosis, structural brain abnormalities such as type I Chiari malformation (118420), mental retardation, congenital heart disease (patent ductus arteriosus, atrial septal defect), and aneurysms with dissection throughout the arterial tree. Heterozygous mutations were found in the TGFBR1 gene in 4 of the 10 families and in the TGFBR2 gene (190182) in 6. Tissues derived from affected individuals showed increased expression of both collagen (see 120150) and connective tissue growth factor (CTGF; 121009), as well as nuclear enrichment of phosphorylated SMAD2, indicative of increased TGF-beta signaling. </p><p>Loeys et al. (2006) undertook the clinical and molecular characterization of the families of 40 probands presenting with typical manifestations of Loeys-Dietz syndrome (LDS1). In view of the phenotypic overlap between this syndrome and vascular Ehlers-Danlos syndrome (EDS; 130050), they screened an additional cohort of 40 patients who had been diagnosed provisionally with vascular EDS but lacked the characteristic abnormalities of type III collagen (120180). Of these 40 probands, 4 carried a heterozygous mutation in TGFBR1 (3 of which involved codon 487; see, e.g., 190181.0004 and 190181.0007) and were classified as having Loeys-Dietz syndrome-2, a phenotypic classification denoting absence of craniofacial involvement. Overall, 13 mutations were found in TGFBR1. </p><p>Ades et al. (2006) discussed the phenotypes and genotypes of 5 individuals with conditions within the Marfan syndrome/marfanoid-craniosynostosis/marfanoid-metal retardation spectrum in light of evidence of abnormal TGF-beta signaling in the pathogenesis of Marfan-like phenotypes. In 2 unrelated patients with Furlong syndrome (see 609192) they described the same missense mutation in TGFBR1 (190181.0005). The other 3 patients had alterations of the FBN1 gene (134797). Ades et al. (2006) concluded that their findings supported the notion that perturbation of extracellular matrix homeostasis and/or remodeling caused by abnormal TGF-beta signaling is the core pathogenetic mechanism in Marfan syndrome and related entities. </p><p>In patients with phenotypes classified as type 2 Marfan syndrome, Loeys-Dietz syndrome, or thoracic aortic aneurysm with dissection (TAAD), Matyas et al. (2006) detected 3 novel mutations in the TGFBR1 gene. A heterozygous arg487-to-gln (R487Q) mutation (190181.0006) was present in a patient with TAAD; mutation of the same residue to pro (R487P; 190181.0004) had been previously reported in a family whose phenotype was identified as Loeys-Dietz syndrome. </p><p>Singh et al. (2006) searched for TGFBR1 and TGFBR2 mutations in 41 unrelated patients fulfilling the diagnostic criteria of the Ghent nosology (De Paepe et al., 1996) or with a tentative diagnosis of Marfan syndrome, in whom mutations in the FBN1 coding region were not identified. In TGFBR1, 2 mutations and 2 polymorphisms were detected. In TGFBR2, 5 mutations and 6 polymorphisms were identified. Reexamination of patients with a TGFBR1 or TGFBR2 mutation revealed extensive clinical overlap between these patients. </p><p><strong><em>Susceptibility To Multiple Self-Healing Squamous Epithelioma</em></strong></p><p>
|
|
In affected members of 18 different families with autosomal dominant multiple self-healing squamous epithelioma (MSSE; 132800), Goudie et al. (2011) identified 11 different heterozygous mutations in the TGFBR1 gene (see, e.g., 190181.0009-190181.0012). The phenotype is characterized by the development of multiple squamous carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before showing spontaneous regression, leaving scars. The mutations identified by Goudie et al. (2011) occurred in either the extracellular ligand-binding domain (exon 2) or in the serine/threonine kinase domain (exons 4, 6, and 7), and all were predicted or demonstrated to result in loss of receptor function. Several mutation carriers were unaffected, and tumor tissue from some patients showed loss of heterozygosity for the wildtype allele. Overall, the findings were consistent with wildtype TGFBR1 acting as a tumor suppressor, until somatic deletion by a classic second hit results in carcinogenesis. Goudie et al. (2011) noted that TGFBR1 mutations causing Loeys-Dietz syndrome result in activation of the TGFB1 signaling pathway, whereas TGFBR1 mutations causing MSSE result in loss of the TGFB1 signaling pathway. </p><p><strong><em>Susceptibility To Abdominal Aortic Aneurysm</em></strong></p><p>
|
|
For discussion of a possible association between variation in the TGFBR1 gene and susceptibility to abdominal aortic aneurysm, see AAA (100070).</p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
For discussion of a possible association between variation near the TGFBR1 gene and age-related macular degeneration, see ARMD1 (603075).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>To better define the function of TGF-beta in hematopoiesis and angiogenesis, Larsson et al. (2001) used gene targeting to inactivate the Tgfbr1 gene in mice. Mice lacking Tgfbr1 died at midgestation, exhibited severe defects in the vascular development of the yolk sac and placenta, and lacked circulating red blood cells. Analysis of yolk sac-derived hematopoietic precursors of Tgfbr1 null mice revealed normal hematopoietic potential. However, endothelial cells from these embryos showed enhanced cell proliferation, improper migratory behavior, and impaired fibronectin (135600) production in vitro. Larsson et al. (2001) noted that these endothelial defects are associated with the vascular defects seen in vivo. They concluded that Tgfbr1-dependent signaling is required for angiogenesis, but not for the development of hematopoietic progenitor cells and functional hematopoiesis. </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 LOEYS-DIETZ SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TGFBR1, MET318ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918710,
|
|
|
|
|
|
|
|
ClinVar: RCV000119102
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with Loeys-Dietz syndrome (LDS1; 609192), Loeys et al. (2005) found a 953T-G transversion on exon 5 of the TGFBR1 gene that resulted in a met318-to-arg (M318R) substitution in the kinase domain of the protein. The mutation occurred de novo. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 LOEYS-DIETZ SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TGFBR1, ASP400GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918711,
|
|
|
|
|
|
|
|
ClinVar: RCV000013346
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with Loeys-Dietz syndrome (LDS1; 609192), Loeys et al. (2005) identified an 1199A-G transition in exon 7 of the TGFBR1 gene, resulting in an asp400-to-gly (D400G) substitution in the kinase domain of the protein. The mutation occurred de novo. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 LOEYS-DIETZ SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TGFBR1, THR200ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918712,
|
|
|
|
|
|
|
|
ClinVar: RCV000013347
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with Loeys-Dietz syndrome (LDS1; 609192), Loeys et al. (2005) identified a 599C-T transition in exon 4 of the TGFBR1 gene that resulted in a thr200-to-ile (T200I) substitution at the junction of the glycine-serine-rich domain and the kinase domain of the TGFBR1 protein. The mutation occurred de novo. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 LOEYS-DIETZ SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TGFBR1, ARG487PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs113605875,
|
|
|
|
|
|
|
|
ClinVar: RCV000013348
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with Loeys-Dietz syndrome (LDS1; 609192), Loeys et al. (2005) found a 1460G-C transversion in exon 9 of the TGFBR1 gene that resulted in an arg487-to-pro (R487P) amino acid substitution. The R487P mutation segregated with the disorder in a father and 2 sons. </p><p>Loeys et al. (2006) classified LDS in the family reported by Loeys et al. (2005) as LDS1 on the basis of craniofacial findings, but found the same mutation in another patient with LDS classified as LDS2 (lacking typical craniofacial findings). Other missense mutations involving the same codon, R487Q (190181.0007) and R487W (190181.0007), have been identified. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 LOEYS-DIETZ SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TGFBR1, SER241LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs111854391,
|
|
|
|
|
|
gnomAD: rs111854391,
|
|
|
|
|
|
ClinVar: RCV000013350, RCV000030540, RCV000244262, RCV000442105, RCV000617152, RCV000845292, RCV003224094
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 patients judged to have Furlong syndrome (see LDS1, 609192), Ades et al. (2006) found an identical heterozygous missense mutation, ser241 to leu (S241L), in the TGFBR1 gene. The mutation, which arose from a C-to-T transition at nucleotide position 722, alters a highly conserved nonpolar serine in the serine-threonine kinase domain to a polar leucine residue. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 LOEYS-DIETZ SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TGFBR1, ARG487GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs113605875,
|
|
|
|
|
|
|
|
ClinVar: RCV000013351, RCV000196834, RCV000211857, RCV000463090, RCV001194075, RCV004730845
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 43-year-old patient with thoracic aortic aneurysm and dissection (see 609192), Matyas et al. (2006) found a de novo heterozygous 1460G-A transition in exon 9 of the TGFBR1 gene that caused an arg487-to-gln substitution in the protein (R487Q). Mutation at this codon had been found previously (190181.0004). The mutation occurred in the kinase domain of the protein and was predicted to affect protein function. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 LOEYS-DIETZ SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TGFBR1, ARG487TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs111426349,
|
|
|
|
|
|
gnomAD: rs111426349,
|
|
|
|
|
|
ClinVar: RCV000013352, RCV000200764, RCV000211856, RCV000251089, RCV000763611, RCV004802936
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a woman with Loeys-Dietz syndrome without typical craniofacial findings (LDS1; 609192), Loeys et al. (2006) found an arg487-to-trp (R487W) missense mutation in the TGFBR1 gene. The patient had aortic root aneurysm with dissection, other arterial aneurysm, arterial tortuosity, vascular rupture during pregnancy, uterine hemorrhage, bowel rupture, inguinal hernia, velvety skin, skin hyperextensibility, atrophic scars, and joint laxity. Another missense mutation at the same codon had been described (R487P; 190181.0004). </p><p>In 11 affected members of a 4-generation family with thoracic aortic aneurysm as well as aneurysms and dissections of other arteries, originally reported by Nicod et al. (1989), Tran-Fadulu et al. (2009) identified heterozygosity for the R487W mutation in the TGFBR1 gene. Imaging of the cerebrovascular circulation in 2 affected family members showed tortuous vessels and fusiform dilation of the basilar artery. Tran-Fadulu et al. (2009) stated that examination of 6 family members revealed no features of Loeys-Dietz syndrome type 1; specifically, none had bifid uvula, craniosynostosis, hypertelorism, or translucent skin. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 LOEYS-DIETZ SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TGFBR1, GLY174VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918713,
|
|
|
|
|
|
gnomAD: rs121918713,
|
|
|
|
|
|
ClinVar: RCV000013353, RCV005054137
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 45-year-old Italian man with Loeys-Dietz syndrome (LDS1; 609192), Drera et al. (2008) identified a heterozygous 521G-T transversion in exon 3 of the TGFBR1 gene, resulting in a gly174-to-val (G174V) substitution in the intracellular region of the receptor. The mutation was not identified in 200 chromosomes from Italian controls nor in the patient's unaffected daughter. The patient had a prominent and narrow nose, thin lips, bifid uvula and cleft palate, hypermobility of small joints, and soft skin. He also had a history of dissection of both internal iliac arteries and the right femoral artery. There was no aortic root dilatation or tortuosity of the great vessels. The patient had been classified phenotypically as type 2. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MULTIPLE SELF-HEALING SQUAMOUS EPITHELIOMA, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TGFBR1, ASN45SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906696,
|
|
|
|
|
|
gnomAD: rs387906696,
|
|
|
|
|
|
ClinVar: RCV000022802, RCV000454530, RCV000654793, RCV000766900, RCV001374784, RCV002477006, RCV003996113
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 symptomatic members of a Scottish family with autosomal dominant multiple self-healing squamous epithelioma (MSSE; 132800), Goudie et al. (2011) identified a heterozygous 134A-G transition in exon 2 of the TGFBR1 gene, resulting in an asn45-to-ser (N45S) substitution in the extracellular ligand-binding domain. One additional asymptomatic family member also carried the mutation, which was not found in 80 Scottish controls. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MULTIPLE SELF-HEALING SQUAMOUS EPITHELIOMA, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TGFBR1, GLY52ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776865,
|
|
|
|
|
|
|
|
ClinVar: RCV000022803, RCV000777702
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected individuals from 7 Scottish families with autosomal dominant multiple self-healing squamous epithelioma (MSSE; 132800), previously reported by Ferguson-Smith et al., 1971 and Goudie et al., 1993, Goudie et al. (2011) identified a heterozygous 154G-C transversion in exon 2 of the TGFBR1 gene, resulting in a gly52-to-arg (G52R) substitution in the extracellular ligand-binding domain. Asymptomatic family members in several families also carried the mutation, which was not found in 80 Scottish controls. Studies of tumor tissue from an affected individual showed that the mutant protein was expressed and localized to the plasma membrane, but there was some loss of heterozygosity for the wildtype allele. SMAD reporter assay showed that the mutant G52R receptor protein gave lower activation than the wildtype protein in response to TGFB1 stimulation, consistent with a loss of function. Overall, the findings were consistent with wildtype TGFBR1 acting as a tumor suppressor, until somatic deletion by a classic second hit results in carcinogenesis. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MULTIPLE SELF-HEALING SQUAMOUS EPITHELIOMA, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TGFBR1, IVS4AS, A-C, -2
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776866,
|
|
|
|
|
|
|
|
ClinVar: RCV000022804, RCV004802947
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 affected individuals from an English family with autosomal dominant multiple self-healing squamous epithelioma (MSSE; 132800), Goudie et al. (2011) identified a heterozygous A-to-C transversion (806-2A-C) in intron 4 of the TGFBR1 gene, resulting in a splice site mutation in a region containing the serine/threonine kinase domain. The mutation was predicted to result in loss of receptor signaling. The mutation was not found in 80 Scottish controls. Tumor tissue from an affected individual showed loss of heterozygosity for the wildtype allele. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MULTIPLE SELF-HEALING SQUAMOUS EPITHELIOMA, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TGFBR1, ARG414TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906697,
|
|
|
|
|
|
|
|
ClinVar: RCV000022805, RCV000474057
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 affected individuals from an English family with autosomal dominant multiple self-healing squamous epithelioma (MSSE; 132800), Goudie et al. (2011) identified a heterozygous 1240C-T transition in exon 7 of the TGFBR1 gene, resulting in an arg414-to-ter (R414X) substitution in the serine/threonine kinase domain. The mutation resulted in nonsense-mediated mRNA decay, causing a loss of receptor signaling. The mutation was not found in 80 Scottish controls. </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">
|
|
Ades, L. C., Sullivan, K., Biggin, A., Haan, E. A., Brett, M., Holman, K. J., Dixon, J., Robertson, S., Holmes, A. D., Rogers, J., Bennetts, B.
|
|
<strong>FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited.</strong>
|
|
Am. J. Med. Genet. 140A: 1047-1058, 2006.
|
|
|
|
|
|
[PubMed: 16596670]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31202]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Barrios-Rodiles, M., Brown, K. R., Ozdamar, B., Bose, R., Liu, Z., Donovan, R. S., Shinjo, F., Liu, Y., Dembowy, J., Taylor, I. W., Luga, V., Przulj, N., Robinson, M., Suzuki, H., Hayashizaki, Y., Jurisica, I., Wrana, J. L.
|
|
<strong>High-throughput mapping of a dynamic signaling network in mammalian cells.</strong>
|
|
Science 307: 1621-1625, 2005.
|
|
|
|
|
|
[PubMed: 15761153]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1105776]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
De Paepe, A., Devereux, R. B., Dietz, H. C., Hennekam, R. C. M., Pyeritz, R. E.
|
|
<strong>Revised diagnostic criteria for the Marfan syndrome.</strong>
|
|
Am. J. Med. Genet. 62: 417-426, 1996.
|
|
|
|
|
|
[PubMed: 8723076]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19960424)62:4<417::AID-AJMG15>3.0.CO;2-R]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Drera, B., Tadini, G., Barlati, S., Colombi, M.
|
|
<strong>Identification of a novel TGFBR1 mutation in a Loeys-Dietz syndrome type II patient with vascular Ehlers-Danlos syndrome phenotype. (Letter)</strong>
|
|
Clin. Genet. 73: 290-293, 2008.
|
|
|
|
|
|
[PubMed: 18070134]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2007.00942.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ebner, R., Chen, R.-H., Shum, L., Lawler, S., Zioncheck, T. F., Lee, A., Lopez, A. R., Derynck, R.
|
|
<strong>Cloning of a type I TGF-beta receptor and its effect on TGF-beta binding to the type II receptor.</strong>
|
|
Science 260: 1344-1348, 1993.
|
|
|
|
|
|
[PubMed: 8388127]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.8388127]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ferguson-Smith, M. A., Wallace, D. C., James, Z. H., Renwick, J. H.
|
|
<strong>Multiple self-healing squamous epithelioma.</strong>
|
|
Birth Defects Orig. Art. Ser. VII(8): 157-163, 1971.
|
|
|
|
|
|
[PubMed: 5173258]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Franzen, P., ten Dijke, P., Ichijo, H., Yamashita, H., Schulz, P., Heldin, C.-H., Miyazono, K.
|
|
<strong>Cloning of a TGF-beta type I receptor that forms a heteromeric complex with the TGF-beta type II receptor.</strong>
|
|
Cell 75: 681-692, 1993.
|
|
|
|
|
|
[PubMed: 8242743]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(93)90489-d]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goudie, D. R., D'Alessandro, M., Merriman, B., Lee, H., Szeverenyi, I., Avery, S., O'Connor, B. D., Nelson, S. F., Coats, S. E., Stewart, A., Christie, L., Pichert, G., and 11 others.
|
|
<strong>Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1.</strong>
|
|
Nature Genet. 43: 365-369, 2011.
|
|
|
|
|
|
[PubMed: 21358634]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.780]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goudie, D. R., Yuille, M. A. R., Leversha, M. A., Furlong, R. A., Carter, N. P., Lush, M. J., Affara, N. A., Ferguson-Smith, M. A.
|
|
<strong>Multiple self-healing squamous epitheliomata (ESS1) mapped to chromosome 9q22-q31 in families with common ancestry.</strong>
|
|
Nature Genet. 3: 165-169, 1993.
|
|
|
|
|
|
[PubMed: 8499949]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0293-165]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Inman, G. J., Nicolas, F. J., Hill, C. S.
|
|
<strong>Nucleocytoplasmic shuttling of Smads 2, 3, and 4 permits sensing of TGF-beta receptor activity.</strong>
|
|
Molec. Cell 10: 283-294, 2002.
|
|
|
|
|
|
[PubMed: 12191474]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s1097-2765(02)00585-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johnson, D. W., Qumsiyeh, M., Benkhalifa, M., Marchuk, D. A.
|
|
<strong>Assignment of human transforming growth factor-beta type I and type III receptor genes (TGFBR1 and TGFBR3) to 9q33-q34 and 1p32-p33, respectively.</strong>
|
|
Genomics 28: 356-357, 1995.
|
|
|
|
|
|
[PubMed: 8530052]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1995.1157]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kuan, J., Kono, D. H.
|
|
<strong>Tgfbr1 maps to chromosome 4.</strong>
|
|
Mammalian Genome 9: 95-96, 1998.
|
|
|
|
|
|
[PubMed: 9434964]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s003359900695]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Larsson, J., Goumans, M.-J., Sjostrand, L. J., van Rooijen, M. A., Ward, D., Leveen, P., Xu, X., Dijke, P., Mummery, C. L., Karlsson, S.
|
|
<strong>Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient mice.</strong>
|
|
EMBO J. 20: 1663-1673, 2001.
|
|
|
|
|
|
[PubMed: 11285230]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/emboj/20.7.1663]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Loeys, B. L., Chen, J., Neptune, E. R., Judge, D. P., Podowski, M., Holm, T., Meyers, J., Leitch, C. C., Katsanis, N., Sharifi, N., Xu, F. L., Myers, L. A., and 12 others.
|
|
<strong>A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2.</strong>
|
|
Nature Genet. 37: 275-281, 2005.
|
|
|
|
|
|
[PubMed: 15731757]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1511]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Loeys, B. L., Schwarze, U., Holm, T., Callewaert, B. L., Thomas, G. H., Pannu, H., De Backer, J. F., Oswald, G. L., Symoens, S., Manouvrier, S., Roberts, A. E., Faravelli, F., and 9 others.
|
|
<strong>Aneurysm syndromes caused by mutations in the TGF-beta receptor.</strong>
|
|
New Eng. J. Med. 355: 788-798, 2006.
|
|
|
|
|
|
[PubMed: 16928994]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa055695]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matyas, G., Arnold, E., Carrel, T., Baumgartner, D., Boileau, C., Berger, W., Steinmann, B.
|
|
<strong>Identification and in silico analyses of novel TGFBR1 and TGFBR2 mutations in Marfan syndrome-related disorders.</strong>
|
|
Hum. Mutat. 27: 760-769, 2006.
|
|
|
|
|
|
[PubMed: 16791849]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20353]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nicod, P., Bloor, C., Godfrey, M., Hollister, D., Pyeritz, R. E., Dittrich, H., Polikar, R., Peterson, K. L.
|
|
<strong>Familial aortic dissecting aneurysm.</strong>
|
|
J. Am. Coll. Cardiol. 13: 811-819, 1989.
|
|
|
|
|
|
[PubMed: 2647812]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0735-1097(89)90221-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pasche, B., Luo, Y., Rao, P. H., Nimer, S. D., Dmitrovsky, E., Caron, P., Luzzatto, L., Offit, K., Cordon-Cardo, C., Renault, B., Satagopan, J. M., Murty, V. V., Massague, J.
|
|
<strong>Type I transforming growth factor beta receptor maps to 9q22 and exhibits a polymorphism and a rare variant within a polyalanine tract.</strong>
|
|
Cancer Res. 58: 2727-2732, 1998.
|
|
|
|
|
|
[PubMed: 9661882]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Singh, K. K., Rommel, K., Mishra, A., Karck, M., Haverich, A., Schmidtke, J., Arslan-Kirchner, M.
|
|
<strong>TGFBR1 and TGFBR2 mutations in patients with features of Marfan syndrome and Loeys-Dietz syndrome.</strong>
|
|
Hum. Mutat. 27: 770-777, 2006.
|
|
|
|
|
|
[PubMed: 16799921]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20354]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tran-Fadulu, V., Pannu, H., Kim, D. H., Vick, G. W., III, Lonsford, C. M., Lafont, A. L., Boccalandro, C., Smart, S., Peterson, K. L., Hain, J. Z., Willing, M. C., Coselli, J. S., LeMaire, S. A., Ahn, C., Byers, P. H., Milewicz, D. M.
|
|
<strong>Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations.</strong>
|
|
J. Med. Genet. 46: 607-613, 2009.
|
|
|
|
|
|
[PubMed: 19542084]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2008.062844]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Valle, L., Serena-Acedo, T., Liyanarachchi, S., Hampel, H., Comeras, I., Li, Z., Zeng, Q., Zhang, H.-T., Pennison, M. J., Sadim, M., Pasche, B., Tanner, S. M., de la Chapelle, A.
|
|
<strong>Germline allele-specific expression of TGFBR1 confers an increased risk of colorectal cancer.</strong>
|
|
Science 321: 1361-1365, 2008.
|
|
|
|
|
|
[PubMed: 18703712]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1159397]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vellucci, V. F., Reiss, M.
|
|
<strong>Cloning and genomic organization of the human transforming growth factor-beta type I receptor gene.</strong>
|
|
Genomics 46: 278-283, 1997.
|
|
|
|
|
|
[PubMed: 9417915]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1997.5023]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, T., Donahoe, P. K., Zervos, A. S.
|
|
<strong>Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12.</strong>
|
|
Science 265: 674-676, 1994.
|
|
|
|
|
|
[PubMed: 7518616]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.7518616]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 4/22/2011<br>Marla J. F. O'Neill - updated : 1/28/2010<br>Ada Hamosh - updated : 10/1/2008<br>Cassandra L. Kniffin - updated : 5/6/2008<br>Victor A. McKusick - updated : 9/20/2006<br>Victor A. McKusick - updated : 8/24/2006<br>Victor A. McKusick - updated : 6/5/2006<br>Ada Hamosh - updated : 6/1/2005<br>Victor A. McKusick - updated : 2/4/2005<br>Patricia A. Hartz - updated : 12/16/2002<br>Stylianos E. Antonarakis - updated : 9/11/2002<br>Paul J. Converse - updated : 7/17/2000<br>Carol A. Bocchini - updated : 11/30/1999<br>Victor A. McKusick - updated : 2/19/1998<br>Victor A. McKusick - updated : 2/4/1998
|
|
</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 : 6/10/1993
|
|
</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">
|
|
alopez : 06/29/2021<br>carol : 09/28/2018<br>carol : 12/15/2014<br>alopez : 4/22/2014<br>alopez : 4/7/2014<br>alopez : 1/11/2012<br>wwang : 4/25/2011<br>ckniffin : 4/22/2011<br>wwang : 2/2/2010<br>terry : 1/28/2010<br>alopez : 10/3/2008<br>alopez : 10/3/2008<br>terry : 10/1/2008<br>wwang : 5/13/2008<br>ckniffin : 5/6/2008<br>alopez : 3/31/2008<br>alopez : 3/7/2008<br>alopez : 10/11/2006<br>terry : 9/20/2006<br>alopez : 9/7/2006<br>alopez : 9/5/2006<br>terry : 8/24/2006<br>alopez : 6/8/2006<br>terry : 6/5/2006<br>carol : 1/18/2006<br>wwang : 6/2/2005<br>wwang : 6/1/2005<br>terry : 6/1/2005<br>alopez : 3/2/2005<br>alopez : 2/7/2005<br>terry : 2/4/2005<br>mgross : 12/18/2002<br>terry : 12/16/2002<br>mgross : 9/11/2002<br>mgross : 7/17/2000<br>carol : 12/1/1999<br>carol : 12/1/1999<br>carol : 11/30/1999<br>carol : 11/30/1999<br>alopez : 11/3/1998<br>dkim : 9/11/1998<br>terry : 2/19/1998<br>mark : 2/5/1998<br>terry : 2/4/1998<br>mark : 8/25/1995<br>carol : 9/30/1994<br>carol : 6/10/1993
|
|
</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>
|
|
|
|
|