3832 lines
313 KiB
Text
3832 lines
313 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
|
|
|
|
- *604633 - EGF-CONTAINING FIBULIN-LIKE EXTRACELLULAR MATRIX PROTEIN 2; EFEMP2
|
|
|
|
|
|
- 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=604633"><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">*604633</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="#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/604633">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=ENSG00000172638;t=ENST00000307998" 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=30008" 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=604633" 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=ENSG00000172638;t=ENST00000307998" 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_016938,NR_037718" 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_016938" 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=604633" 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=05221&isoform_id=05221_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/EFEMP2" 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/3676824,4456473,7328921,7634793,12017760,14714634,37182916,49456823,62087822,119594861,119594862,119594863,119594864,119594865,119594866,119594867,119594868,134047775,158257590,189054797,193785477,193786820,320118911" 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/O95967" 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=30008" 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=ENSG00000172638;t=ENST00000307998" 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=EFEMP2" 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=EFEMP2" 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+30008" 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/EFEMP2" 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:30008" 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/30008" 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=chr11&hgg_gene=ENST00000307998.11&hgg_start=65866441&hgg_end=65872800&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:3219" 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/efemp2" 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=604633[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=604633[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/EFEMP2/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/ENSG00000172638" 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=EFEMP2" 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=EFEMP2" 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=EFEMP2" 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=EFEMP2&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/PA27653" 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:3219" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:1891209" 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/EFEMP2#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:1891209" 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/30008/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=30008" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-030219-125" 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://reactome.org/content/query?q=EFEMP2&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>
|
|
604633
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
EGF-CONTAINING FIBULIN-LIKE EXTRACELLULAR MATRIX PROTEIN 2; EFEMP2
|
|
|
|
</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">
|
|
FIBULIN 4; FBLN4
|
|
</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=EFEMP2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">EFEMP2</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/11/611?start=-3&limit=10&highlight=611">11q13.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr11:65866441-65872800&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'})">11:65,866,441-65,872,800</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/11/611?start=-3&limit=10&highlight=611">
|
|
11q13.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Cutis laxa, autosomal recessive, type IB
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/614437"> 614437 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
</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/604633" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/604633" 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>Members of the fibulin family of proteins, like EFEMP2, are extracellular matrix proteins characterized by tandem arrays of EGF (<a href="/entry/131530">131530</a>)-like domains and a C-terminal fibulin (see FBLN1; <a href="/entry/135820">135820</a>)-type module (<a href="#9" class="mim-tip-reference" title="Kobayashi, N., Kostka, G., Garbe, J. H. O., Keene, D. R., Bachinger, H. P., Hanisch, F.-G., Markova, D., Tsuda, T., Timpl, R., Chu, M.-L., Sasaki, T. <strong>A comparative analysis of the fibulin protein family: biochemical characterization, binding interactions, and tissue localization.</strong> J. Biol. Chem. 282: 11805-11816, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17324935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17324935</a>] [<a href="https://doi.org/10.1074/jbc.M611029200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17324935">Kobayashi et al., 2007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17324935" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 large number of extracellular matrix proteins contain variations of the EGF domain, e.g., fibrillin (FBN1; <a href="/entry/134797">134797</a>) and Notch (<a href="/entry/190198">190198</a>). As part of their efforts in transcriptional mapping of the human 11q13.1-q13.2 genomic region, <a href="#8" class="mim-tip-reference" title="Katsanis, N., Venable, S., Smith, J. R., Lupski, J. R. <strong>Isolation of a paralog of the Doyne honeycomb retinal dystrophy gene from the multiple retinopathy critical region on 11q13.</strong> Hum. Genet. 106: 66-72, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10982184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10982184</a>] [<a href="https://doi.org/10.1007/s004390051011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10982184">Katsanis et al. (2000)</a> identified a novel partial cDNA from a human brain cDNA library. They called the cDNA 'EGF-containing fibulin-like extracellular matrix protein-2' (EFEMP2) because of its significant homology to EFEMP1 (<a href="/entry/601548">601548</a>). Sequence analysis detected 6 putative calcium-binding EGF domains and 4 EGF modules. <a href="#8" class="mim-tip-reference" title="Katsanis, N., Venable, S., Smith, J. R., Lupski, J. R. <strong>Isolation of a paralog of the Doyne honeycomb retinal dystrophy gene from the multiple retinopathy critical region on 11q13.</strong> Hum. Genet. 106: 66-72, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10982184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10982184</a>] [<a href="https://doi.org/10.1007/s004390051011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10982184">Katsanis et al. (2000)</a> observed expression of a 2.0-kb EFEMP2 transcript in all adult tissues tested by Northern blot analysis, with highest levels in heart. RT-PCR detected a 105-bp amplicon from the 3-prime untranslated region in fetal brain, kidney, and heart, but not in lung. EFEMP1 is likewise expressed in a wide range of adult and fetal tissues. In contrast to EFEMP1, however, EFEMP2 was not significantly overexpressed in senescent or quiescent fibroblasts, suggesting a diversity of function within this EGF-like domain subfamily. <a href="#8" class="mim-tip-reference" title="Katsanis, N., Venable, S., Smith, J. R., Lupski, J. R. <strong>Isolation of a paralog of the Doyne honeycomb retinal dystrophy gene from the multiple retinopathy critical region on 11q13.</strong> Hum. Genet. 106: 66-72, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10982184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10982184</a>] [<a href="https://doi.org/10.1007/s004390051011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10982184">Katsanis et al. (2000)</a> also cloned the mouse Efemp2 homolog. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10982184" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using radioimmunoassays, <a href="#9" class="mim-tip-reference" title="Kobayashi, N., Kostka, G., Garbe, J. H. O., Keene, D. R., Bachinger, H. P., Hanisch, F.-G., Markova, D., Tsuda, T., Timpl, R., Chu, M.-L., Sasaki, T. <strong>A comparative analysis of the fibulin protein family: biochemical characterization, binding interactions, and tissue localization.</strong> J. Biol. Chem. 282: 11805-11816, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17324935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17324935</a>] [<a href="https://doi.org/10.1074/jbc.M611029200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17324935">Kobayashi et al. (2007)</a> found variable Fbln4 expression in all 14 mouse tissues examined, with highest expression in aorta, and lowest expression in heart and thymus. Immunohistochemical analysis localized Fbln4 in perichondrium of developing bone in day-15 mouse embryos and in lung parenchyma in day-14 mouse embryos. Electron microscopy after rotary shadowing revealed that recombinant mouse Fbln4, like Fbln3 (EFEMP1; <a href="/entry/601548">601548</a>) and Fbln5 (<a href="/entry/604580">604580</a>), appeared as a 20-nm rod with a globular domain at one end, which represented the N-terminal EGF modules. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17324935" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>By analysis of a somatic cell hybrid panel and by placement on a series of genomic clones by PCR, <a href="#8" class="mim-tip-reference" title="Katsanis, N., Venable, S., Smith, J. R., Lupski, J. R. <strong>Isolation of a paralog of the Doyne honeycomb retinal dystrophy gene from the multiple retinopathy critical region on 11q13.</strong> Hum. Genet. 106: 66-72, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10982184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10982184</a>] [<a href="https://doi.org/10.1007/s004390051011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10982184">Katsanis et al. (2000)</a> mapped the EFEMP2 gene to chromosome 11q13, in an area where several retinopathies have shown genetic linkage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10982184" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#9" class="mim-tip-reference" title="Kobayashi, N., Kostka, G., Garbe, J. H. O., Keene, D. R., Bachinger, H. P., Hanisch, F.-G., Markova, D., Tsuda, T., Timpl, R., Chu, M.-L., Sasaki, T. <strong>A comparative analysis of the fibulin protein family: biochemical characterization, binding interactions, and tissue localization.</strong> J. Biol. Chem. 282: 11805-11816, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17324935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17324935</a>] [<a href="https://doi.org/10.1074/jbc.M611029200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17324935">Kobayashi et al. (2007)</a> found that mouse Fbln3 and Fbln4 and both mouse and human FBLN5 were secreted into the culture media of transfected HEK293 cells. Solid-phase binding assays showed that these proteins bound differentially to extracellular proteins. Mouse Fbln4 bound to collagen XIV (see <a href="/entry/120324">120324</a>), nidogen-2 (NID2; <a href="/entry/605399">605399</a>), tropoelastin (ELN; <a href="/entry/130160">130160</a>), and collagen XV (see <a href="/entry/120325">120325</a>)-derived endostatin, but not to fibronectin (<a href="/entry/135600">135600</a>) or most basement membrane proteins examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17324935" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 immunoprecipitation analysis, <a href="#13" class="mim-tip-reference" title="Schiavinato, A., Keene, D. R., Imhof, T., Doliana, R., Sasaki, T., Sengle, G. <strong>Fibulin-4 deposition requires EMILIN-1 in the extracellular matrix of osteoblasts.</strong> Sci. Rep. 7: 5526, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28717224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28717224</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28717224[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41598-017-05835-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28717224">Schiavinato et al. (2017)</a> identified fibulin-4 as a direct binding partner of Emilin1 (<a href="/entry/130660">130660</a>). Further analysis showed that fibulin-4 and Emilin1 colocalized in mouse calvarial bone and that fibulin-4 deposition required Emilin1 in extracellular matrix of osteoblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28717224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Doyne Honeycomb Retinal Dystrophy</em></strong></p><p>
|
|
Given that EFEMP1 is the site of mutations causing Doyne honeycomb retinal dystrophy (<a href="/entry/126600">126600</a>), <a href="#8" class="mim-tip-reference" title="Katsanis, N., Venable, S., Smith, J. R., Lupski, J. R. <strong>Isolation of a paralog of the Doyne honeycomb retinal dystrophy gene from the multiple retinopathy critical region on 11q13.</strong> Hum. Genet. 106: 66-72, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10982184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10982184</a>] [<a href="https://doi.org/10.1007/s004390051011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10982184">Katsanis et al. (2000)</a> suggested EFEMP2 as a candidate for retinal dystrophies. <a href="#14" class="mim-tip-reference" title="Toto, L., Parodi, M. B., Baralle, F., Casari, G., Ravalico, G., Romano, M. <strong>Genetic heterogeneity in malattia leventinese.</strong> Clin. Genet. 62: 399-403, 2002. Note: Erratum: Clin. Genet. 66: 251 only, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12431256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12431256</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2002.620508.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12431256">Toto et al. (2002)</a> studied linkage of both the EFEMP2 and EFEMP1 genes to malattia leventinese in a 3-generation Swiss-Italian family. Linkage was found only to EFEMP1 in 2 of 5 affected family members. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12431256+10982184" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Autosomal Recessive Cutis Laxa Type IB</em></strong></p><p>
|
|
Cutis laxa is a condition characterized by redundant, pendulous, and inelastic skin. A severe autosomal recessive form of cutis laxa (ARCL1A; <a href="/entry/219100">219100</a>) is caused by mutation in the fibulin-5 gene (FBLN5; <a href="/entry/604580">604580</a>). <a href="#6" class="mim-tip-reference" title="Hucthagowder, V., Sausgruber, N., Kim, K. H., Angle, B., Marmorstein, L. Y., Urban, Z. <strong>Fibulin-4: a novel gene for an autosomal recessive cutis laxa syndrome.</strong> Am. J. Hum. Genet. 78: 1075-1080, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16685658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16685658</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16685658[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/504304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16685658">Hucthagowder et al. (2006)</a> hypothesized that mutations in other members of the fibulin gene family may cause cutis laxa as well. In a child of Iraqi descent with cutis laxa and severe systemic connective tissue abnormalities (ARCL1B; <a href="/entry/614437">614437</a>), <a href="#6" class="mim-tip-reference" title="Hucthagowder, V., Sausgruber, N., Kim, K. H., Angle, B., Marmorstein, L. Y., Urban, Z. <strong>Fibulin-4: a novel gene for an autosomal recessive cutis laxa syndrome.</strong> Am. J. Hum. Genet. 78: 1075-1080, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16685658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16685658</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16685658[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/504304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16685658">Hucthagowder et al. (2006)</a> detected a homozygous missense mutation in the FBLN4 gene (<a href="#0001">604633.0001</a>). The role of fibulin-4 in elastic fiber formation is evolutionarily conserved in mammals (<a href="#10" class="mim-tip-reference" title="McLaughlin, P. J., Chen, Q., Horiguchi, M., Starcher, B. C., Stanton, J. B., Broekelmann, T. J., Marmorstein, A. D., McKay, B., Mecham, R., Nakamura, T., Marmorstein, L. Y. <strong>Targeted disruption of fibulin-4 abolishes elastogenesis and causes perinatal lethality in mice.</strong> Molec. Cell. Biol. 26: 1700-1709, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16478991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16478991</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16478991[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/10.1128/MCB.26.5.1700-1709.2006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16478991">McLaughlin et al., 2006</a>); however, additional observations in the patient of <a href="#6" class="mim-tip-reference" title="Hucthagowder, V., Sausgruber, N., Kim, K. H., Angle, B., Marmorstein, L. Y., Urban, Z. <strong>Fibulin-4: a novel gene for an autosomal recessive cutis laxa syndrome.</strong> Am. J. Hum. Genet. 78: 1075-1080, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16685658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16685658</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16685658[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/504304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16685658">Hucthagowder et al. (2006)</a> suggested that fibulin-4 may have additional pleiotropic functions in vascular patterning and collagen biosynthesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16685658+16478991" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 an infant girl who died at day 27 of life with apparent arachnodactyly, cutis laxa, and severe systemic vascular abnormalities similar to those of the patient described by <a href="#6" class="mim-tip-reference" title="Hucthagowder, V., Sausgruber, N., Kim, K. H., Angle, B., Marmorstein, L. Y., Urban, Z. <strong>Fibulin-4: a novel gene for an autosomal recessive cutis laxa syndrome.</strong> Am. J. Hum. Genet. 78: 1075-1080, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16685658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16685658</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16685658[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/504304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16685658">Hucthagowder et al. (2006)</a>, and who was negative for mutation in the FBLN5 gene, <a href="#3" class="mim-tip-reference" title="Dasouki, M., Markova, D., Garola, R., Sasaki, T., Charbonneau, N. L., Sakai, L. Y., Chu, M.-L. <strong>Compound heterozygous mutations in fibulin-4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa.</strong> Am. J. Med. Genet. 143A: 2635-2641, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17937443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17937443</a>] [<a href="https://doi.org/10.1002/ajmg.a.31980" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17937443">Dasouki et al. (2007)</a> identified compound heterozygosity for a missense mutation and a 4-bp duplication in the FBLN4 gene (<a href="#0002">604633.0002</a> and <a href="#0003">604633.0003</a>, respectively). <a href="#3" class="mim-tip-reference" title="Dasouki, M., Markova, D., Garola, R., Sasaki, T., Charbonneau, N. L., Sakai, L. Y., Chu, M.-L. <strong>Compound heterozygous mutations in fibulin-4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa.</strong> Am. J. Med. Genet. 143A: 2635-2641, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17937443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17937443</a>] [<a href="https://doi.org/10.1002/ajmg.a.31980" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17937443">Dasouki et al. (2007)</a> concluded that deficiency in fibulin-4 leads to a perinatal lethal condition associated with elastic tissue abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16685658+17937443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Hoyer, J., Kraus, C., Hammersen, G., Geppert, J.-P., Rauch, A. <strong>Lethal cutis laxa with contractual arachnodactyly, overgrowth and soft tissue bleeding due to a novel homozygous fibulin-4 gene mutation.</strong> Clin. Genet. 76: 276-281, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19664000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19664000</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2009.01204.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19664000">Hoyer et al. (2009)</a> reported the third case of cutis laxa due to mutation in FBLN4, an infant girl who died immediately after birth with extreme bradycardia and who was found to be homozygous for a missense mutation (<a href="#0004">604633.0004</a>). <a href="#5" class="mim-tip-reference" title="Hoyer, J., Kraus, C., Hammersen, G., Geppert, J.-P., Rauch, A. <strong>Lethal cutis laxa with contractual arachnodactyly, overgrowth and soft tissue bleeding due to a novel homozygous fibulin-4 gene mutation.</strong> Clin. Genet. 76: 276-281, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19664000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19664000</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2009.01204.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19664000">Hoyer et al. (2009)</a> stated that this case extended the phenotypic spectrum of FBLN4 mutations to include microcephaly, overgrowth, and arachnodactyly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19664000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#12" class="mim-tip-reference" title="Renard, M., Holm, T., Veith, R., Callewaert, B. L., Ades, L. C., Baspinar, O., Pickart, A., Dasouki, M., Hoyer, J., Rauch, A., Trapane, P., Earing, M. G., Coucke, P. J., Sakai, L. Y., Dietz, H. C., De Paepe, A. M., Loeys, B. L. <strong>Altered TGF-beta signaling and cardiovascular manifestations in patients with autosomal recessive cutis laxa type I caused by fibulin-4 deficiency.</strong> Europ. J. Hum. Genet. 18: 895-901, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20389311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20389311</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20389311[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2010.45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20389311">Renard et al. (2010)</a> sequenced the FBLN4 gene in 17 patients with prominent cutis laxa but no major cardiovascular findings, and detected no mutations. Analysis of FBLN4 in a second cohort of 22 patients who had mild skin involvement but significant cardiovascular features, including arterial tortuosity, stenosis, and aneurysms, revealed homozygosity or compound heterozygosity for mutations in the FBLN4 gene in 3 patients (<a href="#0005">604633.0005</a>-<a href="#0008">604633.0008</a>). <a href="#12" class="mim-tip-reference" title="Renard, M., Holm, T., Veith, R., Callewaert, B. L., Ades, L. C., Baspinar, O., Pickart, A., Dasouki, M., Hoyer, J., Rauch, A., Trapane, P., Earing, M. G., Coucke, P. J., Sakai, L. Y., Dietz, H. C., De Paepe, A. M., Loeys, B. L. <strong>Altered TGF-beta signaling and cardiovascular manifestations in patients with autosomal recessive cutis laxa type I caused by fibulin-4 deficiency.</strong> Europ. J. Hum. Genet. 18: 895-901, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20389311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20389311</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20389311[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2010.45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20389311">Renard et al. (2010)</a> concluded that patients with recessive FBLN4 mutations are predominantly characterized by aortic aneurysms and arterial tortuosity and stenosis. Immunostaining of aortic and lung tissue showed an increase in TGF-beta (<a href="/entry/190180">190180</a>), which was confirmed by phosphorylated SMAD2 (<a href="/entry/601366">601366</a>) immunoblotting of fibroblast cultures; <a href="#12" class="mim-tip-reference" title="Renard, M., Holm, T., Veith, R., Callewaert, B. L., Ades, L. C., Baspinar, O., Pickart, A., Dasouki, M., Hoyer, J., Rauch, A., Trapane, P., Earing, M. G., Coucke, P. J., Sakai, L. Y., Dietz, H. C., De Paepe, A. M., Loeys, B. L. <strong>Altered TGF-beta signaling and cardiovascular manifestations in patients with autosomal recessive cutis laxa type I caused by fibulin-4 deficiency.</strong> Europ. J. Hum. Genet. 18: 895-901, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20389311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20389311</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20389311[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2010.45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20389311">Renard et al. (2010)</a> stated that this was the first evidence of involvement of altered TGFB signaling in the pathogenesis of FBLN4 mutations in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20389311" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Kappanayil, M., Nampoothiri, S., Kannan, R., Renard, M., Coucke, P., Malfait, F., Menon, S., Ravindran, H. K., Kurup, R., Faiyaz-Ul-Haque, M., Kumar, K., De Paepe, A. <strong>Characterization of a distinct lethal arteriopathy syndrome in twenty-two infants associated with an identical, novel mutation in the FBLN4 gene, confirms fibulin-4 as a critical determinant of human vascular elastogenesis.</strong> Orphanet J. Rare Dis. 7: 61, 2012. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22943132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22943132</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22943132[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/10.1186/1750-1172-7-61" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22943132">Kappanayil et al. (2012)</a> reported 22 unrelated infants from the Malabar region of the southern Indian state of Kerala. All were Muslims and came from the community known as the Mappilas. Twenty-one of 22 were homozygous for a missense mutation in exon 7 of FBLN4 (<a href="#0009">604633.0009</a>). One patient was compound heterozygous for this mutation and a second, de novo, mutation (<a href="#0010">604633.0010</a>) on her paternal chromosome. Both mutations occurred in the same calcium-binding EGF domain of the protein. Neither mutation was found among 200 control alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22943132" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#4" class="mim-tip-reference" title="Horiguchi, M., Inoue, T., Ohbayashi, T., Hirai, M., Noda, K., Marmorstein, L. Y., Yabe, D., Takagi, K., Akama, T. O., Kita, T., Kimura, T., Nakamura, T. <strong>Fibulin-4 conducts proper elastogenesis via interaction with cross-linking enzyme lysyl oxidase.</strong> Proc. Nat. Acad. Sci. 106: 19029-19034, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19855011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19855011</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19855011[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0908268106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19855011">Horiguchi et al. (2009)</a> found that mice homozygous for conditional knockout of Fbln4 specifically in smooth muscle and mice compound heterozygous for smooth muscle-specific Flbn4 knockout and constitutive Fbln4 knockout had normal growth, fertility, and survival up to 1 year. Arteries of homozygous conditional knockout mice had residual (18.5%) expression of Fbln4, which was sufficient for embryonic development of elastic laminae, but was insufficient to support the development of elastic laminae after birth. Compound heterozygous mice had a greater reduction in Fbln4 expression (8.4%) and were unable to organize elastic laminae in embryogenesis, leading to ascending aortic aneurysm. Moreover, disruption of Fbln4 led to morphologically and physiologically impaired aortic elastic laminae, resulting in significantly stiff aortae. Further analysis revealed that Fbln4 specifically interacted with the propeptide of Lox (<a href="/entry/153455">153455</a>) through its N-terminal domain and colocalized with Lox on elastic fibers. By interacting with the Lox propeptide, Fbln4 tethered it on tropoelastin, thereby playing a role in elastogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19855011" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Papke, C. L., Tsunezumi, J., Ringuette, L.-J., Nagaoka, H., Terajima, M., Yamashiro, Y., Urquhart, G., Yamauchi, M., Davis, E. C., Yanagisawa, H. <strong>Loss of fibulin-4 disrupts collagen synthesis and maturation: implications for pathology resulting from EFEMP2 mutations.</strong> Hum. Molec. Genet. 24: 5867-5879, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26220971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26220971</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26220971[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/hmg/ddv308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26220971">Papke et al. (2015)</a> found that knockout of Efemp2 targeted to mouse smooth muscle (SMKO) resulted in altered fibrillar collagen localization with larger, profoundly disorganized fibrils. Collagen pro-lysyl oxidase (LOX) activity was reduced in Efemp2-null mouse embryonic fibroblasts, and collagen cross-linking was diminished in SMKO aorta, but elastin cross-linking was unaffected, and the level of mature Lox was maintained to that of wildtype aorta. Proteomic screening identified multiple potential Efemp2 binding partners involved in procollagen processing and maturation. The authors confirmed that Efemp2 bound procollagen C-endopeptise enhancer-1 (PCOLCE; <a href="/entry/600270">600270</a>), which enhances proteolytic cleavage of the procollagen C-terminal propeptide. However, procollagen cleavage was not affected by loss of Efemp2. <a href="#11" class="mim-tip-reference" title="Papke, C. L., Tsunezumi, J., Ringuette, L.-J., Nagaoka, H., Terajima, M., Yamashiro, Y., Urquhart, G., Yamauchi, M., Davis, E. C., Yanagisawa, H. <strong>Loss of fibulin-4 disrupts collagen synthesis and maturation: implications for pathology resulting from EFEMP2 mutations.</strong> Hum. Molec. Genet. 24: 5867-5879, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26220971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26220971</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26220971[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/hmg/ddv308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26220971">Papke et al. (2015)</a> concluded that EFEMP2 may function as a scaffolding protein during collagen maturation in the extracellular space. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26220971" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>10 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/604633" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=604633[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 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
EFEMP2, GLU57LYS
|
|
</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> rs119489101 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119489101;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/rs119489101?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=rs119489101" 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=rs119489101" 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=RCV000005756 OR RCV000032268" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005756, RCV000032268" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005756...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a child of nonconsanguineous parents of Iraqi descent with cutis laxa (ARCL1B; <a href="/entry/614437">614437</a>), <a href="#6" class="mim-tip-reference" title="Hucthagowder, V., Sausgruber, N., Kim, K. H., Angle, B., Marmorstein, L. Y., Urban, Z. <strong>Fibulin-4: a novel gene for an autosomal recessive cutis laxa syndrome.</strong> Am. J. Hum. Genet. 78: 1075-1080, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16685658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16685658</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16685658[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/504304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16685658">Hucthagowder et al. (2006)</a> found homozygosity for a 169G-A transition in the FBLN4 gene that resulted in a glu57-to-lys (E57K) amino acid substitution. Each of her parents was heterozygous for this mutation. Multiple alignments showed that the E57 residue was completely conserved in calcium-binding epidermal growth factor (EGF) modules, consistent with this residue being essential for calcium binding. <a href="#6" class="mim-tip-reference" title="Hucthagowder, V., Sausgruber, N., Kim, K. H., Angle, B., Marmorstein, L. Y., Urban, Z. <strong>Fibulin-4: a novel gene for an autosomal recessive cutis laxa syndrome.</strong> Am. J. Hum. Genet. 78: 1075-1080, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16685658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16685658</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16685658[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/504304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16685658">Hucthagowder et al. (2006)</a> pointed out that the same substitution at a homologous residue in fibulin-1, E1073K (<a href="/entry/134797#0038">134797.0038</a>), causes severe, neonatal Marfan syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16685658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
EFEMP2, ARG279CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs119489102 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs119489102;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=rs119489102" 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=rs119489102" 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=RCV000005757 OR RCV000032275" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005757, RCV000032275" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005757...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant girl with cutis laxa, apparent arachnodactyly, and severe systemic vascular abnormalities (ARCL1B; <a href="/entry/614437">614437</a>), who died at day 27 of life, <a href="#3" class="mim-tip-reference" title="Dasouki, M., Markova, D., Garola, R., Sasaki, T., Charbonneau, N. L., Sakai, L. Y., Chu, M.-L. <strong>Compound heterozygous mutations in fibulin-4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa.</strong> Am. J. Med. Genet. 143A: 2635-2641, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17937443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17937443</a>] [<a href="https://doi.org/10.1002/ajmg.a.31980" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17937443">Dasouki et al. (2007)</a> identified compound heterozygosity for an 835C-T transition in exon 8 of the EFEMP2 gene, resulting in an arg279-to-cys (R279C) substitution at a highly conserved residue at the end of the fifth cbEGF module, and a 4-bp duplication in exon 10 (1070dupCCGC; <a href="#0003">604633.0003</a>), predicted to truncate the protein and replace the last 85 amino acids of the FC domain with an incorrect arg residue. The missense mutation was not found in 50 controls. Analysis of the patient's fibroblasts revealed that fibulin-4 protein was barely detectable in culture medium and not seen in cell extract and matrix, and immunostaining of patient fibroblasts showed a total absence of fibulin-4 fibers from the extracellular matrix. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17937443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#12" class="mim-tip-reference" title="Renard, M., Holm, T., Veith, R., Callewaert, B. L., Ades, L. C., Baspinar, O., Pickart, A., Dasouki, M., Hoyer, J., Rauch, A., Trapane, P., Earing, M. G., Coucke, P. J., Sakai, L. Y., Dietz, H. C., De Paepe, A. M., Loeys, B. L. <strong>Altered TGF-beta signaling and cardiovascular manifestations in patients with autosomal recessive cutis laxa type I caused by fibulin-4 deficiency.</strong> Europ. J. Hum. Genet. 18: 895-901, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20389311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20389311</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20389311[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2010.45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20389311">Renard et al. (2010)</a> performed immunohistochemical staining of fibulin-4 on aortic tissue from the patient previously studied by <a href="#3" class="mim-tip-reference" title="Dasouki, M., Markova, D., Garola, R., Sasaki, T., Charbonneau, N. L., Sakai, L. Y., Chu, M.-L. <strong>Compound heterozygous mutations in fibulin-4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa.</strong> Am. J. Med. Genet. 143A: 2635-2641, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17937443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17937443</a>] [<a href="https://doi.org/10.1002/ajmg.a.31980" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17937443">Dasouki et al. (2007)</a> and confirmed the near absence of extracellular fibulin-4 in the aortic wall compared to the control, whereas intracellular staining was similar to that of the control, suggesting that the mutant protein is either not secreted or is secreted into extracellular space to a lesser extent. Immunohistochemical staining for phosphorylated SMAD2 (<a href="/entry/601366">601366</a>) and CTGF (<a href="/entry/121009">121009</a>), an effector of TGF-beta (<a href="/entry/190180">190180</a>) signaling and a TGF-beta-driven gene product, respectively, in patient aorta and lungs showed a more intense and increased nuclear staining compared to control tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17937443+20389311" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
EFEMP2, 4-BP DUP, 1070CCGC
|
|
</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> rs193302865 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193302865;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/rs193302865?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=rs193302865" 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=rs193302865" 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=RCV000005758 OR RCV000032265" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005758, RCV000032265" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005758...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 4-bp duplication in the EFEMP2 gene (1070dupCCGC) that was found in compound heterozygous state in a patient with cutis laxa, apparent arachnodactyly, and severe systemic vascular abnormalities (ARCL1B; <a href="/entry/614437">614437</a>) by <a href="#3" class="mim-tip-reference" title="Dasouki, M., Markova, D., Garola, R., Sasaki, T., Charbonneau, N. L., Sakai, L. Y., Chu, M.-L. <strong>Compound heterozygous mutations in fibulin-4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa.</strong> Am. J. Med. Genet. 143A: 2635-2641, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17937443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17937443</a>] [<a href="https://doi.org/10.1002/ajmg.a.31980" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17937443">Dasouki et al. (2007)</a>, see <a href="#0002">604633.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17937443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
EFEMP2, CYS267TYR
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193302866 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193302866;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=rs193302866" 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=rs193302866" 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=RCV000023384 OR RCV000032274" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023384, RCV000032274" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023384...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant girl with cutis laxa (ARCL1B; <a href="/entry/614437">614437</a>), born of consanguineous Iraqi parents, <a href="#5" class="mim-tip-reference" title="Hoyer, J., Kraus, C., Hammersen, G., Geppert, J.-P., Rauch, A. <strong>Lethal cutis laxa with contractual arachnodactyly, overgrowth and soft tissue bleeding due to a novel homozygous fibulin-4 gene mutation.</strong> Clin. Genet. 76: 276-281, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19664000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19664000</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2009.01204.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19664000">Hoyer et al. (2009)</a> identified homozygosity for an 800G-A transition in exon 7 of the FBLN4 gene, resulting in a cys267-to-tyr (C267Y) substitution involving the fifth of six highly conserved residues in the fifth cbEGF module. The unaffected parents were heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19664000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#12" class="mim-tip-reference" title="Renard, M., Holm, T., Veith, R., Callewaert, B. L., Ades, L. C., Baspinar, O., Pickart, A., Dasouki, M., Hoyer, J., Rauch, A., Trapane, P., Earing, M. G., Coucke, P. J., Sakai, L. Y., Dietz, H. C., De Paepe, A. M., Loeys, B. L. <strong>Altered TGF-beta signaling and cardiovascular manifestations in patients with autosomal recessive cutis laxa type I caused by fibulin-4 deficiency.</strong> Europ. J. Hum. Genet. 18: 895-901, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20389311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20389311</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20389311[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2010.45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20389311">Renard et al. (2010)</a> performed immunoblotting experiments on the culture medium of dermal fibroblasts from the patient previously studied by <a href="#5" class="mim-tip-reference" title="Hoyer, J., Kraus, C., Hammersen, G., Geppert, J.-P., Rauch, A. <strong>Lethal cutis laxa with contractual arachnodactyly, overgrowth and soft tissue bleeding due to a novel homozygous fibulin-4 gene mutation.</strong> Clin. Genet. 76: 276-281, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19664000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19664000</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2009.01204.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19664000">Hoyer et al. (2009)</a>, and observed a complete absence of fibulin-4. Immunoblotting after TGF-beta (TGFB; <a href="/entry/190180">190180</a>) stimulation of patient fibroblast cultures indicated a significantly increased phosphorylated SMAD2 (<a href="/entry/601366">601366</a>) signal compared to controls, suggesting that mutation in FBLN4 has an effect on the TGFB signaling pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20389311+19664000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
EFEMP2, GLU126LYS
|
|
</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> rs193302867 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193302867;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/rs193302867?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=rs193302867" 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=rs193302867" 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=RCV000032269 OR RCV000033125 OR RCV000724423" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032269, RCV000033125, RCV000724423" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032269...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 20-year-old woman with velvety skin and severe arterial tortuosity, aneurysm, and stenosis (ARCL1B; <a href="/entry/614437">614437</a>), originally reported by <a href="#1" class="mim-tip-reference" title="Ades, L. C., Knight, W. B., Byard, R. W., Bateman, J. F., Esquivel, J. A. D., Mee, R. B. B., Haan, E. A., Milewicz, D. M. <strong>Clinicopathologic findings in congenital aneurysms of the great vessels.</strong> Am. J. Med. Genet. 66: 289-299, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8985490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8985490</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19961218)66:3<289::AID-AJMG11>3.0.CO;2-I" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8985490">Ades et al. (1996)</a>, <a href="#12" class="mim-tip-reference" title="Renard, M., Holm, T., Veith, R., Callewaert, B. L., Ades, L. C., Baspinar, O., Pickart, A., Dasouki, M., Hoyer, J., Rauch, A., Trapane, P., Earing, M. G., Coucke, P. J., Sakai, L. Y., Dietz, H. C., De Paepe, A. M., Loeys, B. L. <strong>Altered TGF-beta signaling and cardiovascular manifestations in patients with autosomal recessive cutis laxa type I caused by fibulin-4 deficiency.</strong> Europ. J. Hum. Genet. 18: 895-901, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20389311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20389311</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20389311[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2010.45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20389311">Renard et al. (2010)</a> identified homozygosity for a 376G-A transition in exon 5 of the EFEMP2 gene, resulting in a glu126-to-lys (E126K) substitution at an evolutionarily conserved residue in the DINE consensus sequence of the second cbEGF-like domain. The mutation was not found in 200 control chromosomes. Immunoblotting experiments on dermal fibroblast culture medium showed only a slightly diminished amount of fibulin-4 compared to control, which the authors suggested was consistent with the longer survival of the patient. In addition, immunoblotting after TGFB (<a href="/entry/190180">190180</a>) stimulation of patient fibroblast cultures indicated a significantly increased phosphorylated SMAD2 (<a href="/entry/601366">601366</a>) signal compared to controls, suggesting that mutation in FBLN4 has an effect on the TGFB signaling pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8985490+20389311" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
EFEMP2, GLU126VAL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193302869 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193302869;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=rs193302869" 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=rs193302869" 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=RCV000032270 OR RCV000033126" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032270, RCV000033126" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032270...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a female infant with arterial tortuosity and aneurysm (ARCL1B; <a href="/entry/614437">614437</a>), who suffered a large hemispheric stroke at 5 weeks of age and died at age 18 months from cardiorespiratory failure, <a href="#12" class="mim-tip-reference" title="Renard, M., Holm, T., Veith, R., Callewaert, B. L., Ades, L. C., Baspinar, O., Pickart, A., Dasouki, M., Hoyer, J., Rauch, A., Trapane, P., Earing, M. G., Coucke, P. J., Sakai, L. Y., Dietz, H. C., De Paepe, A. M., Loeys, B. L. <strong>Altered TGF-beta signaling and cardiovascular manifestations in patients with autosomal recessive cutis laxa type I caused by fibulin-4 deficiency.</strong> Europ. J. Hum. Genet. 18: 895-901, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20389311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20389311</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20389311[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2010.45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20389311">Renard et al. (2010)</a> identified compound heterozygosity for a 377A-T transversion in exon 5 of the EFEMP2 gene, resulting in a glu126-to-val (E126V) substitution at an evolutionarily conserved residue in the DINE consensus sequence of the second cbEGF-like domain, and a 1-bp deletion (577delC; <a href="#0007">604633.0007</a>) in exon 6, causing a frameshift predicted to result in a premature termination codon (Q193Sfs*12). The unaffected parents were each heterozygous for 1 of the mutations, neither of which was present in 200 control chromosomes. Clinical features in this patient included a prominent forehead, mild hypertelorism, downslanting palpebral fissures, depressed nasal bridge, low-set and distorted external ears, and long fingers. Echocardiogram showed severe dilation of the ascending aorta and severe tortuosity of the entire aorta with hypoplasia of the transverse aortic arch, proximal descending, thoracic, and abdominal aorta. MRI showed severe tortuosity of the carotid and cerebral arteries. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20389311" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
EFEMP2, 1-BP DEL, 577C
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193302870 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193302870;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=rs193302870" 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=rs193302870" 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=RCV000032271 OR RCV000033127" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032271, RCV000033127" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032271...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp deletion in the EFEMP2 gene (577delC) that was found in compound heterozygous state in a patient with arterial tortuosity and aneurysm (ARCL1B; <a href="/entry/614437">614437</a>) by <a href="#12" class="mim-tip-reference" title="Renard, M., Holm, T., Veith, R., Callewaert, B. L., Ades, L. C., Baspinar, O., Pickart, A., Dasouki, M., Hoyer, J., Rauch, A., Trapane, P., Earing, M. G., Coucke, P. J., Sakai, L. Y., Dietz, H. C., De Paepe, A. M., Loeys, B. L. <strong>Altered TGF-beta signaling and cardiovascular manifestations in patients with autosomal recessive cutis laxa type I caused by fibulin-4 deficiency.</strong> Europ. J. Hum. Genet. 18: 895-901, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20389311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20389311</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20389311[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2010.45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20389311">Renard et al. (2010)</a>, see <a href="#0006">604633.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20389311" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
EFEMP2, ALA397THR
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs193302868 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193302868;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=rs193302868" 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=rs193302868" 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=RCV000032266 OR RCV000033128" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032266, RCV000033128" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032266...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old boy with arterial tortuosity, aneurysm, and joint laxity (ARCL1B; <a href="/entry/614437">614437</a>), originally reported by <a href="#2" class="mim-tip-reference" title="Baspinar, O., Kilinc, M., Bajat, A., Celkan, M. A., Coskun, Y. <strong>Long tortuous aorta in a child with Larsen syndrome.</strong> Canad. J. Cardiol. 21: 299-301, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15776121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15776121</a>]" pmid="15776121">Baspinar et al. (2005)</a>, <a href="#12" class="mim-tip-reference" title="Renard, M., Holm, T., Veith, R., Callewaert, B. L., Ades, L. C., Baspinar, O., Pickart, A., Dasouki, M., Hoyer, J., Rauch, A., Trapane, P., Earing, M. G., Coucke, P. J., Sakai, L. Y., Dietz, H. C., De Paepe, A. M., Loeys, B. L. <strong>Altered TGF-beta signaling and cardiovascular manifestations in patients with autosomal recessive cutis laxa type I caused by fibulin-4 deficiency.</strong> Europ. J. Hum. Genet. 18: 895-901, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20389311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20389311</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20389311[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2010.45" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20389311">Renard et al. (2010)</a> identified homozygosity for a 1189G-A transition in exon 11 of the EFEMP2 gene, resulting in an ala397-to-thr (A397T) substitution at a highly conserved residue in the C-terminal fibulin-like module. His unaffected parents were heterozygous for the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20389311+15776121" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE 1B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
EFEMP2, ASP203ALA
|
|
</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> rs193302864 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs193302864;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/rs193302864?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=rs193302864" 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=rs193302864" 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=RCV000032272 OR RCV000034873 OR RCV003332092" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000032272, RCV000034873, RCV003332092" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000032272...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 21 patients, 11 male and 10 female, with autosomal recessive cutis laxa type 1B (ARCL1B; <a href="/entry/614437">614437</a>), <a href="#7" class="mim-tip-reference" title="Kappanayil, M., Nampoothiri, S., Kannan, R., Renard, M., Coucke, P., Malfait, F., Menon, S., Ravindran, H. K., Kurup, R., Faiyaz-Ul-Haque, M., Kumar, K., De Paepe, A. <strong>Characterization of a distinct lethal arteriopathy syndrome in twenty-two infants associated with an identical, novel mutation in the FBLN4 gene, confirms fibulin-4 as a critical determinant of human vascular elastogenesis.</strong> Orphanet J. Rare Dis. 7: 61, 2012. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22943132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22943132</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22943132[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/10.1186/1750-1172-7-61" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22943132">Kappanayil et al. (2012)</a> identified homozygosity for an A-to-C transversion at nucleotide 608 in exon 7 of the EFEMP2 gene that resulted in an aspartic acid-to-alanine substitution at codon 203 (D203A). All patients were Muslims from the Mappila community of the Malabar region of the Indian state of Kerala; 8 came from consanguineous families. All parents tested were normal and carried this mutation in heterozygosity. Homozygosity was lethal in 17 of the 21 patients, who died at a median age of 4 months. In another patient from the same community, <a href="#7" class="mim-tip-reference" title="Kappanayil, M., Nampoothiri, S., Kannan, R., Renard, M., Coucke, P., Malfait, F., Menon, S., Ravindran, H. K., Kurup, R., Faiyaz-Ul-Haque, M., Kumar, K., De Paepe, A. <strong>Characterization of a distinct lethal arteriopathy syndrome in twenty-two infants associated with an identical, novel mutation in the FBLN4 gene, confirms fibulin-4 as a critical determinant of human vascular elastogenesis.</strong> Orphanet J. Rare Dis. 7: 61, 2012. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22943132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22943132</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22943132[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/10.1186/1750-1172-7-61" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22943132">Kappanayil et al. (2012)</a> detected compound heterozygosity for this mutation and a de novo missense mutation (<a href="#0010">604633.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22943132" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE 1B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
EFEMP2, ARG227CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs397514683 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397514683;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=rs397514683" 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=rs397514683" 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=RCV000034874" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034874" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034874</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 patient with autosomal recessive cutis laxa type 1B (ARCL1B; <a href="/entry/614437">614437</a>) from the Indian Mappila community, <a href="#7" class="mim-tip-reference" title="Kappanayil, M., Nampoothiri, S., Kannan, R., Renard, M., Coucke, P., Malfait, F., Menon, S., Ravindran, H. K., Kurup, R., Faiyaz-Ul-Haque, M., Kumar, K., De Paepe, A. <strong>Characterization of a distinct lethal arteriopathy syndrome in twenty-two infants associated with an identical, novel mutation in the FBLN4 gene, confirms fibulin-4 as a critical determinant of human vascular elastogenesis.</strong> Orphanet J. Rare Dis. 7: 61, 2012. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22943132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22943132</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22943132[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/10.1186/1750-1172-7-61" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22943132">Kappanayil et al. (2012)</a> detected compound heterozygosity for an asp203-to-ala mutation (D203A; <a href="#0009">604633.0009</a>) and a de novo C-to-T transition at nucleotide 679 resulting in an arginine-to-cysteine substitution at codon 227 (R227C). The mutation was found on the paternal allele; paternity was proven. Both the D203A and R227C mutations occurred in the same calcium-binding EGF domain of FBLN4. While this patient had vascular abnormalities similar to those seen in D203A homozygotes, the majority of whom died before the age of 4 months, she remained asymptomatic at the age of 7 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22943132" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Ades1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ades, L. C., Knight, W. B., Byard, R. W., Bateman, J. F., Esquivel, J. A. D., Mee, R. B. B., Haan, E. A., Milewicz, D. M.
|
|
<strong>Clinicopathologic findings in congenital aneurysms of the great vessels.</strong>
|
|
Am. J. Med. Genet. 66: 289-299, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8985490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8985490</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8985490" 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(19961218)66:3<289::AID-AJMG11>3.0.CO;2-I" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Baspinar2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Baspinar, O., Kilinc, M., Bajat, A., Celkan, M. A., Coskun, Y.
|
|
<strong>Long tortuous aorta in a child with Larsen syndrome.</strong>
|
|
Canad. J. Cardiol. 21: 299-301, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15776121/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15776121</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15776121" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Dasouki2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dasouki, M., Markova, D., Garola, R., Sasaki, T., Charbonneau, N. L., Sakai, L. Y., Chu, M.-L.
|
|
<strong>Compound heterozygous mutations in fibulin-4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa.</strong>
|
|
Am. J. Med. Genet. 143A: 2635-2641, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17937443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17937443</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17937443" 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.31980" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Horiguchi2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Horiguchi, M., Inoue, T., Ohbayashi, T., Hirai, M., Noda, K., Marmorstein, L. Y., Yabe, D., Takagi, K., Akama, T. O., Kita, T., Kimura, T., Nakamura, T.
|
|
<strong>Fibulin-4 conducts proper elastogenesis via interaction with cross-linking enzyme lysyl oxidase.</strong>
|
|
Proc. Nat. Acad. Sci. 106: 19029-19034, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19855011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19855011</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19855011[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=19855011" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0908268106" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Hoyer2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hoyer, J., Kraus, C., Hammersen, G., Geppert, J.-P., Rauch, A.
|
|
<strong>Lethal cutis laxa with contractual arachnodactyly, overgrowth and soft tissue bleeding due to a novel homozygous fibulin-4 gene mutation.</strong>
|
|
Clin. Genet. 76: 276-281, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19664000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19664000</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19664000" 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.1399-0004.2009.01204.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Hucthagowder2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hucthagowder, V., Sausgruber, N., Kim, K. H., Angle, B., Marmorstein, L. Y., Urban, Z.
|
|
<strong>Fibulin-4: a novel gene for an autosomal recessive cutis laxa syndrome.</strong>
|
|
Am. J. Hum. Genet. 78: 1075-1080, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16685658/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16685658</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16685658[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=16685658" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/504304" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Kappanayil2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kappanayil, M., Nampoothiri, S., Kannan, R., Renard, M., Coucke, P., Malfait, F., Menon, S., Ravindran, H. K., Kurup, R., Faiyaz-Ul-Haque, M., Kumar, K., De Paepe, A.
|
|
<strong>Characterization of a distinct lethal arteriopathy syndrome in twenty-two infants associated with an identical, novel mutation in the FBLN4 gene, confirms fibulin-4 as a critical determinant of human vascular elastogenesis.</strong>
|
|
Orphanet J. Rare Dis. 7: 61, 2012. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22943132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22943132</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22943132[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=22943132" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1186/1750-1172-7-61" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Katsanis2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Katsanis, N., Venable, S., Smith, J. R., Lupski, J. R.
|
|
<strong>Isolation of a paralog of the Doyne honeycomb retinal dystrophy gene from the multiple retinopathy critical region on 11q13.</strong>
|
|
Hum. Genet. 106: 66-72, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10982184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10982184</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10982184" 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/s004390051011" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Kobayashi2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kobayashi, N., Kostka, G., Garbe, J. H. O., Keene, D. R., Bachinger, H. P., Hanisch, F.-G., Markova, D., Tsuda, T., Timpl, R., Chu, M.-L., Sasaki, T.
|
|
<strong>A comparative analysis of the fibulin protein family: biochemical characterization, binding interactions, and tissue localization.</strong>
|
|
J. Biol. Chem. 282: 11805-11816, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17324935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17324935</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17324935" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M611029200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="McLaughlin2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McLaughlin, P. J., Chen, Q., Horiguchi, M., Starcher, B. C., Stanton, J. B., Broekelmann, T. J., Marmorstein, A. D., McKay, B., Mecham, R., Nakamura, T., Marmorstein, L. Y.
|
|
<strong>Targeted disruption of fibulin-4 abolishes elastogenesis and causes perinatal lethality in mice.</strong>
|
|
Molec. Cell. Biol. 26: 1700-1709, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16478991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16478991</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16478991[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=16478991" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/MCB.26.5.1700-1709.2006" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Papke2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Papke, C. L., Tsunezumi, J., Ringuette, L.-J., Nagaoka, H., Terajima, M., Yamashiro, Y., Urquhart, G., Yamauchi, M., Davis, E. C., Yanagisawa, H.
|
|
<strong>Loss of fibulin-4 disrupts collagen synthesis and maturation: implications for pathology resulting from EFEMP2 mutations.</strong>
|
|
Hum. Molec. Genet. 24: 5867-5879, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26220971/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26220971</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26220971[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=26220971" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddv308" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Renard2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Renard, M., Holm, T., Veith, R., Callewaert, B. L., Ades, L. C., Baspinar, O., Pickart, A., Dasouki, M., Hoyer, J., Rauch, A., Trapane, P., Earing, M. G., Coucke, P. J., Sakai, L. Y., Dietz, H. C., De Paepe, A. M., Loeys, B. L.
|
|
<strong>Altered TGF-beta signaling and cardiovascular manifestations in patients with autosomal recessive cutis laxa type I caused by fibulin-4 deficiency.</strong>
|
|
Europ. J. Hum. Genet. 18: 895-901, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20389311/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20389311</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20389311[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=20389311" 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/ejhg.2010.45" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Schiavinato2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schiavinato, A., Keene, D. R., Imhof, T., Doliana, R., Sasaki, T., Sengle, G.
|
|
<strong>Fibulin-4 deposition requires EMILIN-1 in the extracellular matrix of osteoblasts.</strong>
|
|
Sci. Rep. 7: 5526, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28717224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28717224</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28717224[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=28717224" 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/s41598-017-05835-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Toto2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Toto, L., Parodi, M. B., Baralle, F., Casari, G., Ravalico, G., Romano, M.
|
|
<strong>Genetic heterogeneity in malattia leventinese.</strong>
|
|
Clin. Genet. 62: 399-403, 2002. Note: Erratum: Clin. Genet. 66: 251 only, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12431256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12431256</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12431256" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1034/j.1399-0004.2002.620508.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Bao Lige - updated : 09/04/2024
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Patricia A. Hartz - updated : 02/03/2016<br>Patricia A. Hartz - updated : 11/4/2013<br>Patricia A. Hartz - updated : 11/4/2013<br>Ada Hamosh - updated : 4/26/2013<br>Marla J. F. O'Neill - updated : 2/13/2013<br>Marla J. F. O'Neill - updated : 2/7/2011<br>Marla J. F. O'Neill - updated : 8/5/2009<br>Anne M. Stumpf - updated : 5/22/2006<br>Victor A. McKusick - updated : 5/18/2006<br>Victor A. McKusick - updated : 12/18/2002
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 2/29/2000
|
|
</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">
|
|
mgross : 09/04/2024
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 02/22/2022<br>mgross : 02/03/2016<br>carol : 7/13/2015<br>mcolton : 7/10/2015<br>mgross : 12/9/2013<br>mcolton : 11/4/2013<br>mcolton : 11/4/2013<br>alopez : 4/26/2013<br>alopez : 4/26/2013<br>carol : 2/15/2013<br>terry : 2/13/2013<br>terry : 2/13/2013<br>alopez : 1/26/2012<br>alopez : 1/24/2012<br>wwang : 2/24/2011<br>terry : 2/7/2011<br>wwang : 9/1/2009<br>terry : 8/5/2009<br>alopez : 5/22/2006<br>terry : 5/18/2006<br>carol : 5/4/2005<br>carol : 8/31/2004<br>carol : 8/11/2004<br>carol : 12/23/2002<br>carol : 12/23/2002<br>tkritzer : 12/20/2002<br>terry : 12/18/2002<br>alopez : 3/3/2000<br>alopez : 2/29/2000
|
|
</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> 604633
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
EGF-CONTAINING FIBULIN-LIKE EXTRACELLULAR MATRIX PROTEIN 2; EFEMP2
|
|
|
|
</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">
|
|
FIBULIN 4; FBLN4
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: EFEMP2</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 11q13.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 11:65,866,441-65,872,800 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
11q13.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Cutis laxa, autosomal recessive, type IB
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
614437
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Members of the fibulin family of proteins, like EFEMP2, are extracellular matrix proteins characterized by tandem arrays of EGF (131530)-like domains and a C-terminal fibulin (see FBLN1; 135820)-type module (Kobayashi et al., 2007). </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>A large number of extracellular matrix proteins contain variations of the EGF domain, e.g., fibrillin (FBN1; 134797) and Notch (190198). As part of their efforts in transcriptional mapping of the human 11q13.1-q13.2 genomic region, Katsanis et al. (2000) identified a novel partial cDNA from a human brain cDNA library. They called the cDNA 'EGF-containing fibulin-like extracellular matrix protein-2' (EFEMP2) because of its significant homology to EFEMP1 (601548). Sequence analysis detected 6 putative calcium-binding EGF domains and 4 EGF modules. Katsanis et al. (2000) observed expression of a 2.0-kb EFEMP2 transcript in all adult tissues tested by Northern blot analysis, with highest levels in heart. RT-PCR detected a 105-bp amplicon from the 3-prime untranslated region in fetal brain, kidney, and heart, but not in lung. EFEMP1 is likewise expressed in a wide range of adult and fetal tissues. In contrast to EFEMP1, however, EFEMP2 was not significantly overexpressed in senescent or quiescent fibroblasts, suggesting a diversity of function within this EGF-like domain subfamily. Katsanis et al. (2000) also cloned the mouse Efemp2 homolog. </p><p>Using radioimmunoassays, Kobayashi et al. (2007) found variable Fbln4 expression in all 14 mouse tissues examined, with highest expression in aorta, and lowest expression in heart and thymus. Immunohistochemical analysis localized Fbln4 in perichondrium of developing bone in day-15 mouse embryos and in lung parenchyma in day-14 mouse embryos. Electron microscopy after rotary shadowing revealed that recombinant mouse Fbln4, like Fbln3 (EFEMP1; 601548) and Fbln5 (604580), appeared as a 20-nm rod with a globular domain at one end, which represented the N-terminal EGF modules. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By analysis of a somatic cell hybrid panel and by placement on a series of genomic clones by PCR, Katsanis et al. (2000) mapped the EFEMP2 gene to chromosome 11q13, in an area where several retinopathies have shown genetic linkage. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Kobayashi et al. (2007) found that mouse Fbln3 and Fbln4 and both mouse and human FBLN5 were secreted into the culture media of transfected HEK293 cells. Solid-phase binding assays showed that these proteins bound differentially to extracellular proteins. Mouse Fbln4 bound to collagen XIV (see 120324), nidogen-2 (NID2; 605399), tropoelastin (ELN; 130160), and collagen XV (see 120325)-derived endostatin, but not to fibronectin (135600) or most basement membrane proteins examined. </p><p>By immunoprecipitation analysis, Schiavinato et al. (2017) identified fibulin-4 as a direct binding partner of Emilin1 (130660). Further analysis showed that fibulin-4 and Emilin1 colocalized in mouse calvarial bone and that fibulin-4 deposition required Emilin1 in extracellular matrix of osteoblasts. </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>Doyne Honeycomb Retinal Dystrophy</em></strong></p><p>
|
|
Given that EFEMP1 is the site of mutations causing Doyne honeycomb retinal dystrophy (126600), Katsanis et al. (2000) suggested EFEMP2 as a candidate for retinal dystrophies. Toto et al. (2002) studied linkage of both the EFEMP2 and EFEMP1 genes to malattia leventinese in a 3-generation Swiss-Italian family. Linkage was found only to EFEMP1 in 2 of 5 affected family members. </p><p><strong><em>Autosomal Recessive Cutis Laxa Type IB</em></strong></p><p>
|
|
Cutis laxa is a condition characterized by redundant, pendulous, and inelastic skin. A severe autosomal recessive form of cutis laxa (ARCL1A; 219100) is caused by mutation in the fibulin-5 gene (FBLN5; 604580). Hucthagowder et al. (2006) hypothesized that mutations in other members of the fibulin gene family may cause cutis laxa as well. In a child of Iraqi descent with cutis laxa and severe systemic connective tissue abnormalities (ARCL1B; 614437), Hucthagowder et al. (2006) detected a homozygous missense mutation in the FBLN4 gene (604633.0001). The role of fibulin-4 in elastic fiber formation is evolutionarily conserved in mammals (McLaughlin et al., 2006); however, additional observations in the patient of Hucthagowder et al. (2006) suggested that fibulin-4 may have additional pleiotropic functions in vascular patterning and collagen biosynthesis. </p><p>In an infant girl who died at day 27 of life with apparent arachnodactyly, cutis laxa, and severe systemic vascular abnormalities similar to those of the patient described by Hucthagowder et al. (2006), and who was negative for mutation in the FBLN5 gene, Dasouki et al. (2007) identified compound heterozygosity for a missense mutation and a 4-bp duplication in the FBLN4 gene (604633.0002 and 604633.0003, respectively). Dasouki et al. (2007) concluded that deficiency in fibulin-4 leads to a perinatal lethal condition associated with elastic tissue abnormalities. </p><p>Hoyer et al. (2009) reported the third case of cutis laxa due to mutation in FBLN4, an infant girl who died immediately after birth with extreme bradycardia and who was found to be homozygous for a missense mutation (604633.0004). Hoyer et al. (2009) stated that this case extended the phenotypic spectrum of FBLN4 mutations to include microcephaly, overgrowth, and arachnodactyly. </p><p>Renard et al. (2010) sequenced the FBLN4 gene in 17 patients with prominent cutis laxa but no major cardiovascular findings, and detected no mutations. Analysis of FBLN4 in a second cohort of 22 patients who had mild skin involvement but significant cardiovascular features, including arterial tortuosity, stenosis, and aneurysms, revealed homozygosity or compound heterozygosity for mutations in the FBLN4 gene in 3 patients (604633.0005-604633.0008). Renard et al. (2010) concluded that patients with recessive FBLN4 mutations are predominantly characterized by aortic aneurysms and arterial tortuosity and stenosis. Immunostaining of aortic and lung tissue showed an increase in TGF-beta (190180), which was confirmed by phosphorylated SMAD2 (601366) immunoblotting of fibroblast cultures; Renard et al. (2010) stated that this was the first evidence of involvement of altered TGFB signaling in the pathogenesis of FBLN4 mutations in humans. </p><p>Kappanayil et al. (2012) reported 22 unrelated infants from the Malabar region of the southern Indian state of Kerala. All were Muslims and came from the community known as the Mappilas. Twenty-one of 22 were homozygous for a missense mutation in exon 7 of FBLN4 (604633.0009). One patient was compound heterozygous for this mutation and a second, de novo, mutation (604633.0010) on her paternal chromosome. Both mutations occurred in the same calcium-binding EGF domain of the protein. Neither mutation was found among 200 control alleles. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Horiguchi et al. (2009) found that mice homozygous for conditional knockout of Fbln4 specifically in smooth muscle and mice compound heterozygous for smooth muscle-specific Flbn4 knockout and constitutive Fbln4 knockout had normal growth, fertility, and survival up to 1 year. Arteries of homozygous conditional knockout mice had residual (18.5%) expression of Fbln4, which was sufficient for embryonic development of elastic laminae, but was insufficient to support the development of elastic laminae after birth. Compound heterozygous mice had a greater reduction in Fbln4 expression (8.4%) and were unable to organize elastic laminae in embryogenesis, leading to ascending aortic aneurysm. Moreover, disruption of Fbln4 led to morphologically and physiologically impaired aortic elastic laminae, resulting in significantly stiff aortae. Further analysis revealed that Fbln4 specifically interacted with the propeptide of Lox (153455) through its N-terminal domain and colocalized with Lox on elastic fibers. By interacting with the Lox propeptide, Fbln4 tethered it on tropoelastin, thereby playing a role in elastogenesis. </p><p>Papke et al. (2015) found that knockout of Efemp2 targeted to mouse smooth muscle (SMKO) resulted in altered fibrillar collagen localization with larger, profoundly disorganized fibrils. Collagen pro-lysyl oxidase (LOX) activity was reduced in Efemp2-null mouse embryonic fibroblasts, and collagen cross-linking was diminished in SMKO aorta, but elastin cross-linking was unaffected, and the level of mature Lox was maintained to that of wildtype aorta. Proteomic screening identified multiple potential Efemp2 binding partners involved in procollagen processing and maturation. The authors confirmed that Efemp2 bound procollagen C-endopeptise enhancer-1 (PCOLCE; 600270), which enhances proteolytic cleavage of the procollagen C-terminal propeptide. However, procollagen cleavage was not affected by loss of Efemp2. Papke et al. (2015) concluded that EFEMP2 may function as a scaffolding protein during collagen maturation in the extracellular space. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>10 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFEMP2, GLU57LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs119489101,
|
|
|
|
|
|
gnomAD: rs119489101,
|
|
|
|
|
|
ClinVar: RCV000005756, RCV000032268
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a child of nonconsanguineous parents of Iraqi descent with cutis laxa (ARCL1B; 614437), Hucthagowder et al. (2006) found homozygosity for a 169G-A transition in the FBLN4 gene that resulted in a glu57-to-lys (E57K) amino acid substitution. Each of her parents was heterozygous for this mutation. Multiple alignments showed that the E57 residue was completely conserved in calcium-binding epidermal growth factor (EGF) modules, consistent with this residue being essential for calcium binding. Hucthagowder et al. (2006) pointed out that the same substitution at a homologous residue in fibulin-1, E1073K (134797.0038), causes severe, neonatal Marfan syndrome. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFEMP2, ARG279CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs119489102,
|
|
|
|
|
|
|
|
ClinVar: RCV000005757, RCV000032275
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant girl with cutis laxa, apparent arachnodactyly, and severe systemic vascular abnormalities (ARCL1B; 614437), who died at day 27 of life, Dasouki et al. (2007) identified compound heterozygosity for an 835C-T transition in exon 8 of the EFEMP2 gene, resulting in an arg279-to-cys (R279C) substitution at a highly conserved residue at the end of the fifth cbEGF module, and a 4-bp duplication in exon 10 (1070dupCCGC; 604633.0003), predicted to truncate the protein and replace the last 85 amino acids of the FC domain with an incorrect arg residue. The missense mutation was not found in 50 controls. Analysis of the patient's fibroblasts revealed that fibulin-4 protein was barely detectable in culture medium and not seen in cell extract and matrix, and immunostaining of patient fibroblasts showed a total absence of fibulin-4 fibers from the extracellular matrix. </p><p>Renard et al. (2010) performed immunohistochemical staining of fibulin-4 on aortic tissue from the patient previously studied by Dasouki et al. (2007) and confirmed the near absence of extracellular fibulin-4 in the aortic wall compared to the control, whereas intracellular staining was similar to that of the control, suggesting that the mutant protein is either not secreted or is secreted into extracellular space to a lesser extent. Immunohistochemical staining for phosphorylated SMAD2 (601366) and CTGF (121009), an effector of TGF-beta (190180) signaling and a TGF-beta-driven gene product, respectively, in patient aorta and lungs showed a more intense and increased nuclear staining compared to control tissues. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFEMP2, 4-BP DUP, 1070CCGC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193302865,
|
|
|
|
|
|
gnomAD: rs193302865,
|
|
|
|
|
|
ClinVar: RCV000005758, RCV000032265
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 4-bp duplication in the EFEMP2 gene (1070dupCCGC) that was found in compound heterozygous state in a patient with cutis laxa, apparent arachnodactyly, and severe systemic vascular abnormalities (ARCL1B; 614437) by Dasouki et al. (2007), see 604633.0002. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFEMP2, CYS267TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193302866,
|
|
|
|
|
|
|
|
ClinVar: RCV000023384, RCV000032274
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an infant girl with cutis laxa (ARCL1B; 614437), born of consanguineous Iraqi parents, Hoyer et al. (2009) identified homozygosity for an 800G-A transition in exon 7 of the FBLN4 gene, resulting in a cys267-to-tyr (C267Y) substitution involving the fifth of six highly conserved residues in the fifth cbEGF module. The unaffected parents were heterozygous for the mutation. </p><p>Renard et al. (2010) performed immunoblotting experiments on the culture medium of dermal fibroblasts from the patient previously studied by Hoyer et al. (2009), and observed a complete absence of fibulin-4. Immunoblotting after TGF-beta (TGFB; 190180) stimulation of patient fibroblast cultures indicated a significantly increased phosphorylated SMAD2 (601366) signal compared to controls, suggesting that mutation in FBLN4 has an effect on the TGFB signaling pathway. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFEMP2, GLU126LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193302867,
|
|
|
|
|
|
gnomAD: rs193302867,
|
|
|
|
|
|
ClinVar: RCV000032269, RCV000033125, RCV000724423
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 20-year-old woman with velvety skin and severe arterial tortuosity, aneurysm, and stenosis (ARCL1B; 614437), originally reported by Ades et al. (1996), Renard et al. (2010) identified homozygosity for a 376G-A transition in exon 5 of the EFEMP2 gene, resulting in a glu126-to-lys (E126K) substitution at an evolutionarily conserved residue in the DINE consensus sequence of the second cbEGF-like domain. The mutation was not found in 200 control chromosomes. Immunoblotting experiments on dermal fibroblast culture medium showed only a slightly diminished amount of fibulin-4 compared to control, which the authors suggested was consistent with the longer survival of the patient. In addition, immunoblotting after TGFB (190180) stimulation of patient fibroblast cultures indicated a significantly increased phosphorylated SMAD2 (601366) signal compared to controls, suggesting that mutation in FBLN4 has an effect on the TGFB signaling pathway. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFEMP2, GLU126VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193302869,
|
|
|
|
|
|
|
|
ClinVar: RCV000032270, RCV000033126
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a female infant with arterial tortuosity and aneurysm (ARCL1B; 614437), who suffered a large hemispheric stroke at 5 weeks of age and died at age 18 months from cardiorespiratory failure, Renard et al. (2010) identified compound heterozygosity for a 377A-T transversion in exon 5 of the EFEMP2 gene, resulting in a glu126-to-val (E126V) substitution at an evolutionarily conserved residue in the DINE consensus sequence of the second cbEGF-like domain, and a 1-bp deletion (577delC; 604633.0007) in exon 6, causing a frameshift predicted to result in a premature termination codon (Q193Sfs*12). The unaffected parents were each heterozygous for 1 of the mutations, neither of which was present in 200 control chromosomes. Clinical features in this patient included a prominent forehead, mild hypertelorism, downslanting palpebral fissures, depressed nasal bridge, low-set and distorted external ears, and long fingers. Echocardiogram showed severe dilation of the ascending aorta and severe tortuosity of the entire aorta with hypoplasia of the transverse aortic arch, proximal descending, thoracic, and abdominal aorta. MRI showed severe tortuosity of the carotid and cerebral arteries. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFEMP2, 1-BP DEL, 577C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193302870,
|
|
|
|
|
|
|
|
ClinVar: RCV000032271, RCV000033127
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 1-bp deletion in the EFEMP2 gene (577delC) that was found in compound heterozygous state in a patient with arterial tortuosity and aneurysm (ARCL1B; 614437) by Renard et al. (2010), see 604633.0006. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IB</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFEMP2, ALA397THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193302868,
|
|
|
|
|
|
|
|
ClinVar: RCV000032266, RCV000033128
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old boy with arterial tortuosity, aneurysm, and joint laxity (ARCL1B; 614437), originally reported by Baspinar et al. (2005), Renard et al. (2010) identified homozygosity for a 1189G-A transition in exon 11 of the EFEMP2 gene, resulting in an ala397-to-thr (A397T) substitution at a highly conserved residue in the C-terminal fibulin-like module. His unaffected parents were heterozygous for the mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE 1B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFEMP2, ASP203ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs193302864,
|
|
|
|
|
|
gnomAD: rs193302864,
|
|
|
|
|
|
ClinVar: RCV000032272, RCV000034873, RCV003332092
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 21 patients, 11 male and 10 female, with autosomal recessive cutis laxa type 1B (ARCL1B; 614437), Kappanayil et al. (2012) identified homozygosity for an A-to-C transversion at nucleotide 608 in exon 7 of the EFEMP2 gene that resulted in an aspartic acid-to-alanine substitution at codon 203 (D203A). All patients were Muslims from the Mappila community of the Malabar region of the Indian state of Kerala; 8 came from consanguineous families. All parents tested were normal and carried this mutation in heterozygosity. Homozygosity was lethal in 17 of the 21 patients, who died at a median age of 4 months. In another patient from the same community, Kappanayil et al. (2012) detected compound heterozygosity for this mutation and a de novo missense mutation (604633.0010). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE 1B</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
EFEMP2, ARG227CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs397514683,
|
|
|
|
|
|
|
|
ClinVar: RCV000034874
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 patient with autosomal recessive cutis laxa type 1B (ARCL1B; 614437) from the Indian Mappila community, Kappanayil et al. (2012) detected compound heterozygosity for an asp203-to-ala mutation (D203A; 604633.0009) and a de novo C-to-T transition at nucleotide 679 resulting in an arginine-to-cysteine substitution at codon 227 (R227C). The mutation was found on the paternal allele; paternity was proven. Both the D203A and R227C mutations occurred in the same calcium-binding EGF domain of FBLN4. While this patient had vascular abnormalities similar to those seen in D203A homozygotes, the majority of whom died before the age of 4 months, she remained asymptomatic at the age of 7 years. </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., Knight, W. B., Byard, R. W., Bateman, J. F., Esquivel, J. A. D., Mee, R. B. B., Haan, E. A., Milewicz, D. M.
|
|
<strong>Clinicopathologic findings in congenital aneurysms of the great vessels.</strong>
|
|
Am. J. Med. Genet. 66: 289-299, 1996.
|
|
|
|
|
|
[PubMed: 8985490]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19961218)66:3<289::AID-AJMG11>3.0.CO;2-I]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Baspinar, O., Kilinc, M., Bajat, A., Celkan, M. A., Coskun, Y.
|
|
<strong>Long tortuous aorta in a child with Larsen syndrome.</strong>
|
|
Canad. J. Cardiol. 21: 299-301, 2005.
|
|
|
|
|
|
[PubMed: 15776121]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dasouki, M., Markova, D., Garola, R., Sasaki, T., Charbonneau, N. L., Sakai, L. Y., Chu, M.-L.
|
|
<strong>Compound heterozygous mutations in fibulin-4 causing neonatal lethal pulmonary artery occlusion, aortic aneurysm, arachnodactyly, and mild cutis laxa.</strong>
|
|
Am. J. Med. Genet. 143A: 2635-2641, 2007.
|
|
|
|
|
|
[PubMed: 17937443]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31980]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Horiguchi, M., Inoue, T., Ohbayashi, T., Hirai, M., Noda, K., Marmorstein, L. Y., Yabe, D., Takagi, K., Akama, T. O., Kita, T., Kimura, T., Nakamura, T.
|
|
<strong>Fibulin-4 conducts proper elastogenesis via interaction with cross-linking enzyme lysyl oxidase.</strong>
|
|
Proc. Nat. Acad. Sci. 106: 19029-19034, 2009.
|
|
|
|
|
|
[PubMed: 19855011]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0908268106]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hoyer, J., Kraus, C., Hammersen, G., Geppert, J.-P., Rauch, A.
|
|
<strong>Lethal cutis laxa with contractual arachnodactyly, overgrowth and soft tissue bleeding due to a novel homozygous fibulin-4 gene mutation.</strong>
|
|
Clin. Genet. 76: 276-281, 2009.
|
|
|
|
|
|
[PubMed: 19664000]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2009.01204.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hucthagowder, V., Sausgruber, N., Kim, K. H., Angle, B., Marmorstein, L. Y., Urban, Z.
|
|
<strong>Fibulin-4: a novel gene for an autosomal recessive cutis laxa syndrome.</strong>
|
|
Am. J. Hum. Genet. 78: 1075-1080, 2006.
|
|
|
|
|
|
[PubMed: 16685658]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/504304]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kappanayil, M., Nampoothiri, S., Kannan, R., Renard, M., Coucke, P., Malfait, F., Menon, S., Ravindran, H. K., Kurup, R., Faiyaz-Ul-Haque, M., Kumar, K., De Paepe, A.
|
|
<strong>Characterization of a distinct lethal arteriopathy syndrome in twenty-two infants associated with an identical, novel mutation in the FBLN4 gene, confirms fibulin-4 as a critical determinant of human vascular elastogenesis.</strong>
|
|
Orphanet J. Rare Dis. 7: 61, 2012. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 22943132]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1186/1750-1172-7-61]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Katsanis, N., Venable, S., Smith, J. R., Lupski, J. R.
|
|
<strong>Isolation of a paralog of the Doyne honeycomb retinal dystrophy gene from the multiple retinopathy critical region on 11q13.</strong>
|
|
Hum. Genet. 106: 66-72, 2000.
|
|
|
|
|
|
[PubMed: 10982184]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390051011]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kobayashi, N., Kostka, G., Garbe, J. H. O., Keene, D. R., Bachinger, H. P., Hanisch, F.-G., Markova, D., Tsuda, T., Timpl, R., Chu, M.-L., Sasaki, T.
|
|
<strong>A comparative analysis of the fibulin protein family: biochemical characterization, binding interactions, and tissue localization.</strong>
|
|
J. Biol. Chem. 282: 11805-11816, 2007.
|
|
|
|
|
|
[PubMed: 17324935]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M611029200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McLaughlin, P. J., Chen, Q., Horiguchi, M., Starcher, B. C., Stanton, J. B., Broekelmann, T. J., Marmorstein, A. D., McKay, B., Mecham, R., Nakamura, T., Marmorstein, L. Y.
|
|
<strong>Targeted disruption of fibulin-4 abolishes elastogenesis and causes perinatal lethality in mice.</strong>
|
|
Molec. Cell. Biol. 26: 1700-1709, 2006.
|
|
|
|
|
|
[PubMed: 16478991]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.26.5.1700-1709.2006]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Papke, C. L., Tsunezumi, J., Ringuette, L.-J., Nagaoka, H., Terajima, M., Yamashiro, Y., Urquhart, G., Yamauchi, M., Davis, E. C., Yanagisawa, H.
|
|
<strong>Loss of fibulin-4 disrupts collagen synthesis and maturation: implications for pathology resulting from EFEMP2 mutations.</strong>
|
|
Hum. Molec. Genet. 24: 5867-5879, 2015.
|
|
|
|
|
|
[PubMed: 26220971]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddv308]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Renard, M., Holm, T., Veith, R., Callewaert, B. L., Ades, L. C., Baspinar, O., Pickart, A., Dasouki, M., Hoyer, J., Rauch, A., Trapane, P., Earing, M. G., Coucke, P. J., Sakai, L. Y., Dietz, H. C., De Paepe, A. M., Loeys, B. L.
|
|
<strong>Altered TGF-beta signaling and cardiovascular manifestations in patients with autosomal recessive cutis laxa type I caused by fibulin-4 deficiency.</strong>
|
|
Europ. J. Hum. Genet. 18: 895-901, 2010.
|
|
|
|
|
|
[PubMed: 20389311]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ejhg.2010.45]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schiavinato, A., Keene, D. R., Imhof, T., Doliana, R., Sasaki, T., Sengle, G.
|
|
<strong>Fibulin-4 deposition requires EMILIN-1 in the extracellular matrix of osteoblasts.</strong>
|
|
Sci. Rep. 7: 5526, 2017.
|
|
|
|
|
|
[PubMed: 28717224]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41598-017-05835-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Toto, L., Parodi, M. B., Baralle, F., Casari, G., Ravalico, G., Romano, M.
|
|
<strong>Genetic heterogeneity in malattia leventinese.</strong>
|
|
Clin. Genet. 62: 399-403, 2002. Note: Erratum: Clin. Genet. 66: 251 only, 2004.
|
|
|
|
|
|
[PubMed: 12431256]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2002.620508.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Bao Lige - updated : 09/04/2024<br>Patricia A. Hartz - updated : 02/03/2016<br>Patricia A. Hartz - updated : 11/4/2013<br>Patricia A. Hartz - updated : 11/4/2013<br>Ada Hamosh - updated : 4/26/2013<br>Marla J. F. O'Neill - updated : 2/13/2013<br>Marla J. F. O'Neill - updated : 2/7/2011<br>Marla J. F. O'Neill - updated : 8/5/2009<br>Anne M. Stumpf - updated : 5/22/2006<br>Victor A. McKusick - updated : 5/18/2006<br>Victor A. McKusick - updated : 12/18/2002
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 2/29/2000
|
|
</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">
|
|
mgross : 09/04/2024<br>carol : 02/22/2022<br>mgross : 02/03/2016<br>carol : 7/13/2015<br>mcolton : 7/10/2015<br>mgross : 12/9/2013<br>mcolton : 11/4/2013<br>mcolton : 11/4/2013<br>alopez : 4/26/2013<br>alopez : 4/26/2013<br>carol : 2/15/2013<br>terry : 2/13/2013<br>terry : 2/13/2013<br>alopez : 1/26/2012<br>alopez : 1/24/2012<br>wwang : 2/24/2011<br>terry : 2/7/2011<br>wwang : 9/1/2009<br>terry : 8/5/2009<br>alopez : 5/22/2006<br>terry : 5/18/2006<br>carol : 5/4/2005<br>carol : 8/31/2004<br>carol : 8/11/2004<br>carol : 12/23/2002<br>carol : 12/23/2002<br>tkritzer : 12/20/2002<br>terry : 12/18/2002<br>alopez : 3/3/2000<br>alopez : 2/29/2000
|
|
</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>
|
|
|
|
|