4064 lines
314 KiB
Text
4064 lines
314 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
|
|
|
|
- *612570 - FIBRILLIN 2; FBN2
|
|
|
|
|
|
- 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=612570"><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">*612570</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#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">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/612570">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=ENSG00000138829;t=ENST00000262464" 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=2201" 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=612570" 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=ENSG00000138829;t=ENST00000262464" 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_001999,XM_017009228" 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_001999" 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=612570" 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=00416&isoform_id=00416_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/FBN2" 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/437972,6002331,10732616,62089050,66346695,119582792,119582793,119582794,119582795,194390808,238054385,444738187,444738189,1034644191,1802653870,1802653872,2462601419" 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/P35556" 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=2201" 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=ENSG00000138829;t=ENST00000262464" 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=FBN2" 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=FBN2" 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+2201" 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/FBN2" 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:2201" 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/2201" 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=chr5&hgg_gene=ENST00000262464.9&hgg_start=128257909&hgg_end=128538245&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:3604" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:3604" 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/fbn2" 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=612570[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=612570[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/FBN2/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/ENSG00000138829" 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=FBN2" 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=FBN2" 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=FBN2" 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="http://www.umd.be/FBN2/" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=FBN2&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/PA28017" 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:3604" 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:95490" 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/FBN2#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:95490" 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/2201/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=2201" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00022816;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-090112-3" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:2201" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://reactome.org/content/query?q=FBN2&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 205821003<br />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
612570
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
FIBRILLIN 2; FBN2
|
|
|
|
</span>
|
|
</h3>
|
|
</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=FBN2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">FBN2</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/5/413?start=-3&limit=10&highlight=413">5q23.3</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr5:128257909-128538245&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'})">5:128,257,909-128,538,245</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=121050,616118" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/5/413?start=-3&limit=10&highlight=413">
|
|
5q23.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Contractural arachnodactyly, congenital
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/121050"> 121050 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Macular degeneration, early-onset
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/616118"> 616118 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/612570" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/612570" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>While investigating the role of fibrillin-1 gene (FBN1; <a href="/entry/134797">134797</a>) in the etiology of Marfan syndrome (<a href="/entry/154700">154700</a>), <a href="#3" class="mim-tip-reference" title="Lee, B., Godfrey, M., Vitale, E., Hori, H., Mattei, M.-G., Sarfarazi, M., Tsipouras, P., Ramirez, F., Hollister, D. W. <strong>Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes.</strong> Nature 352: 330-334, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1852206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1852206</a>] [<a href="https://doi.org/10.1038/352330a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1852206">Lee et al. (1991)</a> isolated a partial cDNA for fibrillin-2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1852206" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using the partial FBN2 cDNA isolated by <a href="#3" class="mim-tip-reference" title="Lee, B., Godfrey, M., Vitale, E., Hori, H., Mattei, M.-G., Sarfarazi, M., Tsipouras, P., Ramirez, F., Hollister, D. W. <strong>Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes.</strong> Nature 352: 330-334, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1852206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1852206</a>] [<a href="https://doi.org/10.1038/352330a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1852206">Lee et al. (1991)</a> to screen an MG-63 human osteosarcoma cell line cDNA library, <a href="#17" class="mim-tip-reference" title="Zhang, H., Apfelroth, S. D., Hu, W., Davis, E. C., Sanguineti, C., Bonadio, J., Mecham, R. P., Ramirez, F. <strong>Structure and expression of fibrillin-2, a novel microfibrillar component preferentially located in elastic matrices.</strong> J. Cell Biol. 124: 855-863, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8120105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8120105</a>] [<a href="https://doi.org/10.1083/jcb.124.5.855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8120105">Zhang et al. (1994)</a> obtained a full-length FBN2 clone. The deduced 2,889-amino acid protein contains an N-terminal signal peptide, followed by a proline-rich region, 3 tandem N-terminal EGF (<a href="/entry/131530">131530</a>)-like repeats, and 41 calcium-binding EGF-like repeats interspersed with another EGF-like repeat, a glycine-rich region, 7 TGF (see <a href="/entry/190180">190180</a>)-binding protein repeats, and 2 Fib motifs. FBN2 also has 2 potential cell attachment sequences, multiple N-glycosylation sites, and 2 C-terminal polylysine stretches. The structures of FBN2 and FBN1 are highly similar, with the most significant difference being the glycine-rich sequence near the N terminus of FBN2, where FBN1 has a proline-rich sequence. FBN2 also contains 2 RGD motifs, whereas FBN1 has only 1. Northern blot analysis detected a 10- to 11-kb FBN2 transcript in MG-63 cells. Western blot analysis detected FBN2 at an apparent molecular mass of 350 kD. Immunohistochemical analysis of human fetal tissues showed colocalization of FBN1 with FBN2 in elastic and nonelastic connective tissues, with preferential accumulation of FBN2 in elastic fiber-rich matrices. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8120105+1852206" 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="#18" class="mim-tip-reference" title="Zhang, H., Hu, W., Ramirez, F. <strong>Developmental expression of fibrillin genes suggests heterogeneity of extracellular microfibrils.</strong> J. Cell Biol. 129: 1165-1176, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7744963/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7744963</a>] [<a href="https://doi.org/10.1083/jcb.129.4.1165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7744963">Zhang et al. (1995)</a> cloned mouse Fbn2, which encodes a deduced 2,907-amino acid protein that shares 97% identity with human FBN2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7744963" 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 immunohistochemical analysis, <a href="#10" class="mim-tip-reference" title="Quondamatteo, F., Reinhardt, D. P., Charbonneau, N. L., Pophal, G., Sakai, L. Y., Herken, R. <strong>Fibrillin-1 and fibrillin-2 in human embryonic and early fetal development.</strong> Matrix Biol. 21: 637-646, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12524050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12524050</a>] [<a href="https://doi.org/10.1016/s0945-053x(02)00100-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12524050">Quondamatteo et al. (2002)</a> investigated the distribution of FIB1 and FIB2 in human embryonic and early fetal tissues between gestational weeks 5 and 12. Both fibrillins were widely distributed. In most embryonic and early fetal organs, such as skin, lung, heart, aorta, central nervous system anlage, nerves, and ganglia, both fibrillins followed the same temporo-spatial pattern of distribution. However, in kidney, liver, rib anlagen, and notochord, distribution of FIB1 and FIB2 differed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12524050" 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="Ratnapriya, R., Zhan, X., Fariss, R. N., Branham, K. E., Zipprer, D., Chakarova, C. F., Sergeev, Y. V., Campos, M. M., Othman, M., Friedman, J. S., Maminishkis, A., Waseem, N. H., and 55 others. <strong>Rare and common variants in extracellular matrix gene fibrillin 2 (FBN2) are associated with macular degeneration.</strong> Hum. Molec. Genet. 23: 5827-5837, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24899048/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24899048</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24899048[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/ddu276" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24899048">Ratnapriya et al. (2014)</a> analyzed RNA sequencing (RNA-Seq) expression data from human fetal tissues and observed high levels of FBN2 transcripts in retinal pigment epithelium and choroid but not in retina. Immunostaining in human fetal eyes showed abundant FBN2 in Bruch membrane, choroid, and sclera. Similar FBN2 expression was obtained in the young adult monkey eye, although labeling was less intense. In contrast to human fetal eyes, FBN2 immunostaining was significantly reduced in choroid and sclera of human donors over 75 years of age, and was undetectable in Bruch membrane. Colabeling studies suggested that FBN2 is localized to the central elastin layer of the Bruch membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24899048" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#3" class="mim-tip-reference" title="Lee, B., Godfrey, M., Vitale, E., Hori, H., Mattei, M.-G., Sarfarazi, M., Tsipouras, P., Ramirez, F., Hollister, D. W. <strong>Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes.</strong> Nature 352: 330-334, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1852206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1852206</a>] [<a href="https://doi.org/10.1038/352330a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1852206">Lee et al. (1991)</a> mapped the FBN2 gene to chromosome 5q23-q31 by in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1852206" 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 analysis of mouse/hamster somatic hybrid cell lines, <a href="#4" class="mim-tip-reference" title="Li, X., Pereira, L., Zhang, H., Sanguineti, C., Ramirez, F., Bonadio, J., Francke, U. <strong>Fibrillin genes map to regions of conserved mouse/human synteny on mouse chromosomes 2 and 18.</strong> Genomics 18: 667-672, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307578</a>] [<a href="https://doi.org/10.1016/s0888-7543(05)80371-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8307578">Li et al. (1993)</a> mapped the mouse Fbn2 gene to chromosome 18. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307578" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneFunction" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneFunctionFold" id="mimGeneFunctionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneFunctionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneFunctionFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#17" class="mim-tip-reference" title="Zhang, H., Apfelroth, S. D., Hu, W., Davis, E. C., Sanguineti, C., Bonadio, J., Mecham, R. P., Ramirez, F. <strong>Structure and expression of fibrillin-2, a novel microfibrillar component preferentially located in elastic matrices.</strong> J. Cell Biol. 124: 855-863, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8120105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8120105</a>] [<a href="https://doi.org/10.1083/jcb.124.5.855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8120105">Zhang et al. (1994)</a> demonstrated differences of expression of fibrillin-1 and fibrillin-2 in human ear cartilage. They noted that this may account for the abnormally shaped (i.e., crumpled) auricular helices that are a hallmark of congenital contractural arachnodactyly (CCA, DA9; <a href="/entry/121050">121050</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8120105" 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 in situ hybridization and immunohistochemical analysis, <a href="#18" class="mim-tip-reference" title="Zhang, H., Hu, W., Ramirez, F. <strong>Developmental expression of fibrillin genes suggests heterogeneity of extracellular microfibrils.</strong> J. Cell Biol. 129: 1165-1176, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7744963/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7744963</a>] [<a href="https://doi.org/10.1083/jcb.129.4.1165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7744963">Zhang et al. (1995)</a> showed that Fib1 and Fib2 were differentially expressed in a temporal and spatial manner during mouse and rat development. In the majority of cases, Fib2 transcripts appeared earlier and accumulated for a shorter period of time than Fib1 transcripts. Synthesis of Fib1 correlated with late morphogenesis and the appearance of well-defined organ structures. Conversely, Fib2 synthesis coincided with early morphogenesis and the beginning of elastogenesis. <a href="#18" class="mim-tip-reference" title="Zhang, H., Hu, W., Ramirez, F. <strong>Developmental expression of fibrillin genes suggests heterogeneity of extracellular microfibrils.</strong> J. Cell Biol. 129: 1165-1176, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7744963/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7744963</a>] [<a href="https://doi.org/10.1083/jcb.129.4.1165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7744963">Zhang et al. (1995)</a> proposed that FIB1 provides mostly force-bearing structural support, whereas FIB2 predominantly regulates the early process of elastic fiber assembly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7744963" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Trask, T. M., Ritty, T. M., Broekelmann, T., Tisdale, C., Mecham, R. P. <strong>N-terminal domains of fibrillin 1 and fibrillin 2 direct the formation of homodimers: a possible first step in microfibril assembly.</strong> Biochem. J. 340: 693-701, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10359653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10359653</a>]" pmid="10359653">Trask et al. (1999)</a> found that human FIB1 and FIB2 homodimerized via an N-terminal region and that the interaction was stabilized by disulfide bonds. Dimer formation occurred intracellularly, suggesting that the process of fibrillin aggregation initiates early after biosynthesis of the molecules. No heterodimers of FIB1 and FIB2 were observed, suggesting that the pro- and gly-rich domains of FIB1 and FIB2, respectively, determine the specificity of dimer formation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10359653" 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="Lin, G., Tiedemann, K., Vollbrandt, T., Peters, H., Batge, B., Brinckmann, J., Reinhardt, D. P. <strong>Homo- and heterotypic fibrillin-1 and -2 interactions constitute the basis for the assembly of microfibrils.</strong> J. Biol. Chem. 277: 50795-50804, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12399449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12399449</a>] [<a href="https://doi.org/10.1074/jbc.M210611200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12399449">Lin et al. (2002)</a> showed that the N terminus of human FIB1 could assemble in a linear fashion with the C terminus of another FIB1 molecule to form homotypic FIB1 microfibrils in the presence of calcium. FIB1 could interact similarly with FIB2 to form heterotypic microfibrils, but FIB2 N- and C-terminal constructs showed no significant interaction with one another. In dermal fibroblasts from a 1-year-old donor, both FIB1 and FIB2 were detected in a microfibrillar network. In contrast, osteoblasts from a 42-year-old donor showed a microfibrillar network made up of FIB1 alone. <a href="#5" class="mim-tip-reference" title="Lin, G., Tiedemann, K., Vollbrandt, T., Peters, H., Batge, B., Brinckmann, J., Reinhardt, D. P. <strong>Homo- and heterotypic fibrillin-1 and -2 interactions constitute the basis for the assembly of microfibrils.</strong> J. Biol. Chem. 277: 50795-50804, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12399449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12399449</a>] [<a href="https://doi.org/10.1074/jbc.M210611200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12399449">Lin et al. (2002)</a> concluded that FIB1 can form microfibrillar structures in the absence of FIB2, and that FIB2 can occur in microfibrils with FIB1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12399449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Congenital Contractural Arachnodactyly</em></strong></p><p>
|
|
<a href="#7" class="mim-tip-reference" title="Putnam, E. A., Milewicz, D. M. <strong>A mutation in the FBN2 gene in dermal fibroblasts from a congenital contractural arachnodactyly patient. (Abstract)</strong> Am. J. Hum. Genet. 57: A225, 1995."None>Putnam and Milewicz (1995)</a> and <a href="#16" class="mim-tip-reference" title="Wang, M., Tsipouras, P., Godfrey, M. <strong>Fibrillin-2 (FBN2) mutation in congenital contractural arachnodactyly. (Abstract)</strong> Am. J. Hum. Genet. 57: A231, 1995."None>Wang et al. (1995)</a> identified heterozygous point mutations in the FBN2 gene in cases of congenital contractural arachnodactyly (CCA; <a href="/entry/121050">121050</a>). A mutation in a calcium-binding EGF-like motif (<a href="#0001">612570.0001</a>) was found by the first authors and a mutation in a TGF-binding protein-like motif (<a href="#0002">612570.0002</a>) by the second group.</p><p>In 2 patients with CCA, <a href="#9" class="mim-tip-reference" title="Putnam, E. A., Zhang, H., Ramirez, F., Milewicz, D. M. <strong>Fibrillin-2 (FBN2) mutations result in the Marfan-like disorder, congenital contractural arachnodactyly.</strong> Nature Genet. 11: 456-458, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7493032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7493032</a>] [<a href="https://doi.org/10.1038/ng1295-456" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7493032">Putnam et al. (1995)</a> identified 2 heterozygous missense mutations in FBN2 that caused substitutions of distinct cysteine residues in separate EGF-like repeats. In addition, <a href="#9" class="mim-tip-reference" title="Putnam, E. A., Zhang, H., Ramirez, F., Milewicz, D. M. <strong>Fibrillin-2 (FBN2) mutations result in the Marfan-like disorder, congenital contractural arachnodactyly.</strong> Nature Genet. 11: 456-458, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7493032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7493032</a>] [<a href="https://doi.org/10.1038/ng1295-456" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7493032">Putnam et al. (1995)</a> identified a G-to-A transition at nucleotide 2890 resulting in a val-to-ile change at amino acid 964 (V964I). They found the V964I change to be a common polymorphism with a heterozygosity index of 0.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7493032" 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>Early-Onset Macular Degeneration</em></strong></p><p>
|
|
In a father and 4 sons with early-onset macular degeneration (EOMD; <a href="/entry/616118">616118</a>), <a href="#11" class="mim-tip-reference" title="Ratnapriya, R., Zhan, X., Fariss, R. N., Branham, K. E., Zipprer, D., Chakarova, C. F., Sergeev, Y. V., Campos, M. M., Othman, M., Friedman, J. S., Maminishkis, A., Waseem, N. H., and 55 others. <strong>Rare and common variants in extracellular matrix gene fibrillin 2 (FBN2) are associated with macular degeneration.</strong> Hum. Molec. Genet. 23: 5827-5837, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24899048/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24899048</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24899048[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/ddu276" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24899048">Ratnapriya et al. (2014)</a> identified heterozygosity for a missense mutation in the FBN2 gene (E1144K; <a href="#0011">612570.0011</a>). Analysis of 96 additional patients with EOMD as well as 96 patients with age-related macular degeneration (ARMD; see <a href="/entry/603075">603075</a>) revealed 2 nonsynonymous rare variants, one in an EOMD patient (M1247T; <a href="#0012">612570.0012</a>) and another in a patient with ARMD. <a href="#11" class="mim-tip-reference" title="Ratnapriya, R., Zhan, X., Fariss, R. N., Branham, K. E., Zipprer, D., Chakarova, C. F., Sergeev, Y. V., Campos, M. M., Othman, M., Friedman, J. S., Maminishkis, A., Waseem, N. H., and 55 others. <strong>Rare and common variants in extracellular matrix gene fibrillin 2 (FBN2) are associated with macular degeneration.</strong> Hum. Molec. Genet. 23: 5827-5837, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24899048/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24899048</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24899048[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/ddu276" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24899048">Ratnapriya et al. (2014)</a> also detected suggestive association of a common FBN2 nonsynonymous variant (V965I; <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs154001;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs154001</a>) with ARMD (odds ratio, 1.10; p = 3.79 x 10(-5)). The authors concluded that rare and common variants in FBN2 contribute to both mendelian and complex forms of macular degeneration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24899048" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="allelicVariants" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<span href="#mimAllelicVariantsFold" id="mimAllelicVariantsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
|
|
</span>
|
|
<strong>12 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/612570" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=612570[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 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FBN2, CYS1252TYR
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852825 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852825;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=rs137852825" 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=rs137852825" 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=RCV000000548" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000548" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000548</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with congenital contractural arachnodactyly (CCA; <a href="/entry/121050">121050</a>), <a href="#7" class="mim-tip-reference" title="Putnam, E. A., Milewicz, D. M. <strong>A mutation in the FBN2 gene in dermal fibroblasts from a congenital contractural arachnodactyly patient. (Abstract)</strong> Am. J. Hum. Genet. 57: A225, 1995."None>Putnam and Milewicz (1995)</a> found a heterozygous G-to-A transition at nucleotide 3755 of their FBN2 cDNA that changed the cysteine at residue 1252 to a tyrosine (C1252Y). This altered one of the highly conserved cysteines in an epidermal growth factor-like domain of the fibrillin-2 protein. By analogy, many of the missense mutations found in FBN1 that result in the Marfan syndrome affect conserved cysteines in the EGF-like domains of the fibrillin-1 protein. The C1252Y mutation altered a restriction enzyme recognition sequence which they used to screen unrelated individuals for the nucleotide substitution; 106 chromosomes failed to show the alteration.</p><p>By SSCP analysis followed by direct sequencing, <a href="#9" class="mim-tip-reference" title="Putnam, E. A., Zhang, H., Ramirez, F., Milewicz, D. M. <strong>Fibrillin-2 (FBN2) mutations result in the Marfan-like disorder, congenital contractural arachnodactyly.</strong> Nature Genet. 11: 456-458, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7493032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7493032</a>] [<a href="https://doi.org/10.1038/ng1295-456" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7493032">Putnam et al. (1995)</a> identified the C1252Y mutation in 1 of 11 unrelated CCA patients. The mutation was absent in 43 unrelated control individuals and in the other 10 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7493032" 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 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FBN2, GLU390LYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852826 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852826;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=rs137852826" 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=rs137852826" 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=RCV000000549" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000549" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000549</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with congenital contractural arachnodactyly (CCA; <a href="/entry/121050">121050</a>), <a href="#16" class="mim-tip-reference" title="Wang, M., Tsipouras, P., Godfrey, M. <strong>Fibrillin-2 (FBN2) mutation in congenital contractural arachnodactyly. (Abstract)</strong> Am. J. Hum. Genet. 57: A231, 1995."None>Wang et al. (1995)</a> found a heterozygous G-to-A transition causing an E390K substitution in a transforming growth factor binding protein-like repeat. This domain is equivalent to exon 9 in the B region of FBN1. This position, in both FBN1 and FBN2, is normally occupied by a negatively charged acidic amino acid, aspartic acid, and glutamic acid, respectively. The authors speculated that the substitution of a glutamic acid by a basic and positively charged lysine could significantly alter the structure of the domain and affect higher order microfibrillar structure.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<a id="0003" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 REMOVED FROM DATABASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0004" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FBN2, IVS33, A-T, -2
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776518 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776518;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=rs587776518" 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=rs587776518" 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=RCV000000551" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000551" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000551</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#14" class="mim-tip-reference" title="Wang, M., Clericuzio, C. L., Godfrey, M. <strong>Familial occurrence of typical and severe lethal congenital contractural arachnodactyly caused by missplicing of exon 34 of fibrillin-2.</strong> Am. J. Hum. Genet. 59: 1027-1034, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900230</a>]" pmid="8900230">Wang et al. (1996)</a> described a mother and daughter with classic and severe lethal congenital contractural arachnodactyly (CCA; <a href="/entry/121050">121050</a>), respectively. The FBN2 mutation resulted in the identical missplicing of exon 34 in both patients. Significantly, the mother was somatic mosaic for the mutation, thus explaining her milder phenotype. The mutation consisted of an A-to-T transversion at the -2 position of the consensus acceptor splice site, changing AG to TG at the 3-prime end of intron 33. The mother had been born with congenital contractures of the hands, elbows, and knees. Elbow and knee contractures improved spontaneously, and in childhood she underwent surgical release of finger contractures. In adolescence, mitral valve prolapse was recognized. At the age of 24 years, she delivered a premature daughter who was recognized as having CCA on the first day of life. Pregnancy was complicated by a third-trimester polyhydramnios and spontaneous delivery at 34 weeks of gestation. She was diagnosed with type-B interrupted aortic arch with large ventricular septal defect and moderate atrial septal defect, duodenal atresia and intestinal malrotation, single umbilical artery, vertebral anomalies, and arachnodactyly with contractures of elbows and knees. Both ears showed a crumpled irregular superior helix and prominent antihelix and root of the helix. There was pectus excavatum. Duodenal atresia was repaired on day 3, interrupted aortic arch was repaired at 1 month of age, and gastrostomy tube was placed for gastroesophageal reflux requiring subsequent jejunostomy because of gastric perforation, at the age of 1.5 months. The infant experienced multiple episodes of sepsis and died at the age of 9 months. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8900230" 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 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FBN2, IVS28, A-G, -15
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776519 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776519;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=rs587776519" 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=rs587776519" 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=RCV000000552" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000552" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000552</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a clinically unaffected man with 2 children with congenital contractural arachnodactyly (CCA; <a href="/entry/121050">121050</a>), <a href="#8" class="mim-tip-reference" title="Putnam, E. A., Park, E.-S., Aalfs, C. M., Hennekam, R. C. M., Milewicz, D. M. <strong>Parental somatic and germ-line mosaicism for a FBN2 mutation and analysis of FBN2 transcript levels in dermal fibroblasts.</strong> Am. J. Hum. Genet. 60: 818-827, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9106527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9106527</a>]" pmid="9106527">Putnam et al. (1997)</a> found mosaicism for a heterozygous exon splicing error deleting nucleotides 3722 to 3844 of the FBN2 mRNA. This cDNA deletion resulted in selective removal of 1 of the 43 calcium-binding EGF-like domains of the fibrillin-2 protein. Analysis of genomic DNA indicated that the splicing error resulted from an A-to-G transition 15 nucleotides upstream from 3-prime splice site of the intron. The genomic mutation resulting in the splicing error altered a putative branch point sequence important for lariat formation, an intermediate structure of normal splicing. The mutation was detectable in DNA from the father's hair bulbs and buccal cells but not his white blood cell DNA, indicating that the father was a somatic mosaic. Analysis of transcript levels by use of dermal fibroblasts from the proband demonstrated that the FBN2 allele containing the exon deletion was expressed at a higher level than the allele inherited from the mother. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9106527" 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 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FBN2, IVS30, T-G, -26
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2126895611 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2126895611;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=rs2126895611" 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=rs2126895611" 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=RCV000000553" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000553" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000553</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 5-generation family in which 18 individuals had congenital contractural arachnodactyly (CCA; <a href="/entry/121050">121050</a>), <a href="#6" class="mim-tip-reference" title="Maslen, C., Babcock, D., Raghunath, M., Steinmann, B. <strong>A rare branch-point mutation is associated with missplicing of fibrillin-2 in a large family with congenital contractural arachnodactyly.</strong> Am. J. Hum. Genet. 60: 1389-1398, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9199560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9199560</a>] [<a href="https://doi.org/10.1086/515472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9199560">Maslen et al. (1997)</a> found partial skipping of exon 31 of the FBN2 gene in affected individuals. Approximately 25% mutant transcript was produced, which was apparently sufficient to cause a CCA phenotype. Sequence analysis of genomic DNA revealed an unusual base composition for intron 30 and identified a t-to-g transversion at position -26, in the vicinity of the splicing branch-point site in intron 30. This was the first report of a CCA mutation in a multiplex family, unequivocally establishing that mutations in FBN2 are responsible for the CCA phenotype. Branch-point mutations had only rarely been associated with human disease (e.g., <a href="/entry/600509#0005">600509.0005</a>). <a href="#6" class="mim-tip-reference" title="Maslen, C., Babcock, D., Raghunath, M., Steinmann, B. <strong>A rare branch-point mutation is associated with missplicing of fibrillin-2 in a large family with congenital contractural arachnodactyly.</strong> Am. J. Hum. Genet. 60: 1389-1398, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9199560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9199560</a>] [<a href="https://doi.org/10.1086/515472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9199560">Maslen et al. (1997)</a> pointed out that deletion in exon 31 of the FBN1 gene results in the severe neonatal Marfan syndrome (<a href="/entry/134797#0019">134797.0019</a>) and a recurrent missplicing of exon 32 (<a href="/entry/134797#0020">134797.0020</a>) has been observed in 2 unrelated cases of neonatal Marfan syndrome (<a href="#15" class="mim-tip-reference" title="Wang, M., Price, C. E., Han, J., Cisler, J., Imaizumi, K., Van Thienen, M. N., DePaepe, A., Godfrey, M. <strong>Recurrent mis-splicing of fibrillin exon 32 in two patients with neonatal Marfan syndrome.</strong> Hum. Molec. Genet. 4: 607-613, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7633409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7633409</a>] [<a href="https://doi.org/10.1093/hmg/4.4.607" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7633409">Wang et al., 1995</a>). It is of note, therefore, that deletion of a corresponding exon in FBN2 is associated with a mild phenotype. The family studied by <a href="#6" class="mim-tip-reference" title="Maslen, C., Babcock, D., Raghunath, M., Steinmann, B. <strong>A rare branch-point mutation is associated with missplicing of fibrillin-2 in a large family with congenital contractural arachnodactyly.</strong> Am. J. Hum. Genet. 60: 1389-1398, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9199560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9199560</a>] [<a href="https://doi.org/10.1086/515472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9199560">Maslen et al. (1997)</a> lived in Switzerland. Affected individuals could be identified immediately by their mothers at birth, on the basis of the hands, which were in a clenched (fist-like) position, and on the basis of their ears, which unequivocally were described as resembling 'cabbage leaves.' The auricular deformity resolved with age and was inconspicuous in all affected adults. Camptodactyly also improved with age, but remained the leading phenotypic feature. Contractures of larger joints were present in varying degrees in all affected individuals. Furthermore, all showed kyphoscoliosis, thoracic deformities, and muscular hypoplasia of calves and forearms. All affected individuals had dolichostenomelia and arachnodactyly. In most, arm span significantly exceeded body height but the discrepancy was underestimated because of contractures of elbows and fingers. This same underestimation occurred in assessment of the lower-body segment, as a result of contractures of the knees. Marked truncal adiposity was present in affected females, which contrasted with the long and slender limbs. Two patients, related as first cousins, had undergone surgery for habitual patella luxation and another affected member was observed to have elevated and hypermobile patellas. Most of the affected family members were noted to have fine and thin skin, and supragluteal striae were noted in 3 patients. No cardiovascular abnormalities were detected in any of the affected family members and there was no history or sign of lens dislocation or retinal detachment. A phenotypically particularly instructive pair of dizygotic male twins were pictured. In contrast to the unaffected twin, dolichostenomelia, arachnodactyly, pectus carinatum, hypoplastic calf muscles, elevation of the patella, and a characteristic deformity of the ear were evident. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7633409+9199560" 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 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FBN2, ASP1114HIS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852827 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852827;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=rs137852827" 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=rs137852827" 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=RCV000000554" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000554" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000554</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family in which members over 4 generations had signs and symptoms associated with congenital contractural arachnodactyly (CCA; <a href="/entry/121050">121050</a>), <a href="#1" class="mim-tip-reference" title="Babcock, D., Gasner, C., Francke, U., Maslen, C. <strong>A single mutation that results in an asp-to-his substitution and partial exon skipping in a family with congenital contractual arachnodactyly.</strong> Hum. Genet. 103: 22-28, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9737771/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9737771</a>] [<a href="https://doi.org/10.1007/s004390050777" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9737771">Babcock et al. (1998)</a> identified a heterozygous G-to-C transversion at nucleotide 3340 of the FBN2 gene. The 3340G-C mutation predicted an asp1114-to-his substitution and also altered the 5-prime donor splice site consensus sequence of exon 25. RT-PCR and DNA sequence analyses demonstrated that this missense mutation also caused low level in-frame missplicing of exon 25 with partial skipping of that exon. Consequently, this single point mutation produced a heterogeneous population of mutant fibrillin-2 molecules in a single individual. Despite the complex manifestation of the mutation, it was associated with a relatively mild phenotype. Analysis of FBN2 allele expression in cultured dermal fibroblasts derived from the proband showed that the mutant allele was preferentially expressed, contributing about 84% of the total transcript. This indicates that an overabundance of mutant transcript does not necessarily correlate with a more severe CCA phenotype. The proband was a 67-year-old woman who was 168 cm tall. Pertinent history included bilaterally dislocating patellae during childhood, chronic aches and pains in numerous joints, muscles, and tendons, and tight hamstrings throughout life. Physical examination showed dental crowding, positive wrist sign of Marfan syndrome, mild thoracic scoliosis, long halluces, tight finger joints, straight elbows, genu valgum, and underdeveloped calf muscles. The external ears were abnormal with an extra piece of cartilage present. Eye findings included myopia and astigmatism. Three daughters were similarly affected. The 39-year-old daughter was 168 cm tall and a had a history of orthopedic problems since birth, including hyperextended feet at birth, contractures of elbows, limited movement in hips, dislocated patellae treated surgically, slight scoliosis, and metatarsus varus. She also had stretch marks on her thighs and an extra piece of cartilage in the external ears. Eye findings included myopia with astigmatism. The 5-year-old son of this woman was thin and tall and had metatarsus varus, contractures of the knees, and the same external ear abnormality. The 37-year-old daughter of the proband was 170 cm tall. She had a history of scoliosis and spinal fusion surgery at age 12 years, dislocated patellae treated surgically, metatarsus varus, thin legs, and contractures of the elbows. On examination, positive thumb sign, positive wrist sign, and long halluces were also noted. She had the same unusual external ears and myopia with astigmatism as did her mother and sister. The 35-year-old daughter of the proband was 173 cm tall and had a history of metatarsus varus, contractures of the elbows, limited hip rotation, and mild myopia. No affected members of this family had abnormal cardiovascular findings. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9737771" 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 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FBN2, CYS1141PHE
|
|
</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> rs137852828 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852828;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/rs137852828?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=rs137852828" 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=rs137852828" 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=RCV000000555" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000555" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000555</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a French Canadian girl with typical features of congenital contractural arachnodactyly (CCA; <a href="/entry/121050">121050</a>), <a href="#2" class="mim-tip-reference" title="Belleh, S., Zhou, G., Wang, M., Der Kaloustian, V. M., Pagon, R. A., Godfrey, M. <strong>Two novel fibrillin-2 mutations in congenital contractural arachnodactyly.</strong> Am. J. Med. Genet. 92: 7-12, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10797416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10797416</a>]" pmid="10797416">Belleh et al. (2000)</a> identified a heterozygous 3422G-T transversion in exon 26 of the FBN2 gene, resulting in a cys1141-to-phe (C1141F) amino acid substitution. Neither parent carried the mutation. The pinnae were 'crumpled,' and there was midthoracic kyphoscoliosis. There was restriction to the extension of the thumbs at the metacarpophalangeal joint. The extension at the distal interphalangeal joints of the first to fourth fingers was also limited bilaterally. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10797416" 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 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FBN2, CYS1252TRP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28931602 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28931602;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=rs28931602" 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=rs28931602" 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=RCV000000556" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000556" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000556</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#2" class="mim-tip-reference" title="Belleh, S., Zhou, G., Wang, M., Der Kaloustian, V. M., Pagon, R. A., Godfrey, M. <strong>Two novel fibrillin-2 mutations in congenital contractural arachnodactyly.</strong> Am. J. Med. Genet. 92: 7-12, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10797416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10797416</a>]" pmid="10797416">Belleh et al. (2000)</a> described a teenaged girl with features of congenital contractural arachnodactyly (CCA; <a href="/entry/121050">121050</a>): tall stature, slender body habitus, arachnodactyly, camptodactyly, and progressive kyphoscoliosis. She had mild mental retardation and mild spasticity. Contractures of the fingers were present. As in the other patient reported by <a href="#2" class="mim-tip-reference" title="Belleh, S., Zhou, G., Wang, M., Der Kaloustian, V. M., Pagon, R. A., Godfrey, M. <strong>Two novel fibrillin-2 mutations in congenital contractural arachnodactyly.</strong> Am. J. Med. Genet. 92: 7-12, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10797416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10797416</a>]" pmid="10797416">Belleh et al. (2000)</a> (see <a href="#0008">612570.0008</a>), the legs were slender with reduced muscle mass, particularly in the calves. <a href="#2" class="mim-tip-reference" title="Belleh, S., Zhou, G., Wang, M., Der Kaloustian, V. M., Pagon, R. A., Godfrey, M. <strong>Two novel fibrillin-2 mutations in congenital contractural arachnodactyly.</strong> Am. J. Med. Genet. 92: 7-12, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10797416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10797416</a>]" pmid="10797416">Belleh et al. (2000)</a> identified a heterozygous 3756T-G transversion in exon 29 of the FBN2 gene, resulting in a cys1252-to-trp (C1252W) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10797416" 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 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FBN2, ASN1259LYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606802 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606802;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=rs267606802" 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=rs267606802" 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=RCV000000557" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000000557" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000000557</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with congenital contractural arachnodactyly (CCA; <a href="/entry/121050">121050</a>), <a href="#12" class="mim-tip-reference" title="Sampson, M. G., Coughlin, C. R., II., Kaplan, P., Conlin, L. K., Meyers, K. E. C., Zackai, E. H., Spinner, N. B., Copelovitch, L. <strong>Evidence for a recurrent microdeletion at chromosome 16p11.2 associated with congenital anomalies of the kidney and urinary tract (CAKUT) and Hirschsprung disease.</strong> Am. J. Med. Genet. 152A: 2618-2622, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20799338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20799338</a>] [<a href="https://doi.org/10.1002/ajmg.a.33628" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20799338">Sampson et al. (2010)</a> identified a heterozygous 3777T-A transversion in the FBN2 gene, resulting in an asn1259-to-lys (N1259K) substitution in a conserved residue in the calcium-binding EGF-like domain 15. He had congenital contractures of the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of the fingers and toes, contractures of the elbows, mild crumpling of the ear helices without ear pits or tags, and right intraabdominal testis. The patient's father, paternal grandmother, and a paternal cousin were reported to have contractures, but DNA samples from these individuals were not available. In addition to congenital contractures, the patient was also found to have short-segment Hirschsprung disease, pervasive developmental disorder, auditory processing difficulties, and attention deficit-hyperactivity disorder. Genomewide SNP array identified an extended 1.7-Mb deletion at chromosome 16p11.2 (see <a href="/entry/613444">613444</a>), which the authors postulated was related to the gastrointestinal abnormality. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20799338" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0011" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MACULAR DEGENERATION, EARLY-ONSET</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FBN2, GLU1144LYS
|
|
</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> rs200060005 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs200060005;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/rs200060005?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=rs200060005" 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=rs200060005" 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=RCV000148948 OR RCV000468154 OR RCV000680529 OR RCV002311021 OR RCV003313043" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000148948, RCV000468154, RCV000680529, RCV002311021, RCV003313043" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000148948...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a father and 4 sons with early-onset macular degeneration (EOMD; <a href="/entry/616118">616118</a>), <a href="#11" class="mim-tip-reference" title="Ratnapriya, R., Zhan, X., Fariss, R. N., Branham, K. E., Zipprer, D., Chakarova, C. F., Sergeev, Y. V., Campos, M. M., Othman, M., Friedman, J. S., Maminishkis, A., Waseem, N. H., and 55 others. <strong>Rare and common variants in extracellular matrix gene fibrillin 2 (FBN2) are associated with macular degeneration.</strong> Hum. Molec. Genet. 23: 5827-5837, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24899048/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24899048</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24899048[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/ddu276" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24899048">Ratnapriya et al. (2014)</a> identified heterozygosity for a c.3430G-A transition in the FBN2 gene, resulting in a glu1144-to-lys (E1144K) substitution within the twelfth Ca(2+)-EGF-like domain. The mutation was not found in an unaffected daughter and son. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24899048" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0012" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MACULAR DEGENERATION, EARLY-ONSET</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FBN2, MET1247THR
|
|
</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> rs149054177 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs149054177;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/rs149054177?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=rs149054177" 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=rs149054177" 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=RCV000148949 OR RCV000693997 OR RCV002345459 OR RCV004700475" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000148949, RCV000693997, RCV002345459, RCV004700475" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000148949...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with early-onset macular degeneration (EOMD; <a href="/entry/616118">616118</a>), <a href="#11" class="mim-tip-reference" title="Ratnapriya, R., Zhan, X., Fariss, R. N., Branham, K. E., Zipprer, D., Chakarova, C. F., Sergeev, Y. V., Campos, M. M., Othman, M., Friedman, J. S., Maminishkis, A., Waseem, N. H., and 55 others. <strong>Rare and common variants in extracellular matrix gene fibrillin 2 (FBN2) are associated with macular degeneration.</strong> Hum. Molec. Genet. 23: 5827-5837, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24899048/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24899048</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24899048[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/ddu276" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24899048">Ratnapriya et al. (2014)</a> identified heterozygosity for a c.3740T-C transition in the FBN2 gene, resulting in a met1247-to-thr (M1247T) substitution within the fifteenth Ca(2+)-EGF-like domain. The variant was not present in 4,300 exomes in the NHLBI Exome Variant Server database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24899048" 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="Babcock1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Babcock, D., Gasner, C., Francke, U., Maslen, C.
|
|
<strong>A single mutation that results in an asp-to-his substitution and partial exon skipping in a family with congenital contractual arachnodactyly.</strong>
|
|
Hum. Genet. 103: 22-28, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9737771/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9737771</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9737771" 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/s004390050777" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Belleh2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Belleh, S., Zhou, G., Wang, M., Der Kaloustian, V. M., Pagon, R. A., Godfrey, M.
|
|
<strong>Two novel fibrillin-2 mutations in congenital contractural arachnodactyly.</strong>
|
|
Am. J. Med. Genet. 92: 7-12, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10797416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10797416</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10797416" 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="Lee1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lee, B., Godfrey, M., Vitale, E., Hori, H., Mattei, M.-G., Sarfarazi, M., Tsipouras, P., Ramirez, F., Hollister, D. W.
|
|
<strong>Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes.</strong>
|
|
Nature 352: 330-334, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1852206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1852206</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1852206" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/352330a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Li1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, X., Pereira, L., Zhang, H., Sanguineti, C., Ramirez, F., Bonadio, J., Francke, U.
|
|
<strong>Fibrillin genes map to regions of conserved mouse/human synteny on mouse chromosomes 2 and 18.</strong>
|
|
Genomics 18: 667-672, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307578</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307578" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0888-7543(05)80371-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Lin2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lin, G., Tiedemann, K., Vollbrandt, T., Peters, H., Batge, B., Brinckmann, J., Reinhardt, D. P.
|
|
<strong>Homo- and heterotypic fibrillin-1 and -2 interactions constitute the basis for the assembly of microfibrils.</strong>
|
|
J. Biol. Chem. 277: 50795-50804, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12399449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12399449</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12399449" 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.M210611200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Maslen1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maslen, C., Babcock, D., Raghunath, M., Steinmann, B.
|
|
<strong>A rare branch-point mutation is associated with missplicing of fibrillin-2 in a large family with congenital contractural arachnodactyly.</strong>
|
|
Am. J. Hum. Genet. 60: 1389-1398, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9199560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9199560</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9199560" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/515472" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Putnam1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Putnam, E. A., Milewicz, D. M.
|
|
<strong>A mutation in the FBN2 gene in dermal fibroblasts from a congenital contractural arachnodactyly patient. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 57: A225, 1995.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Putnam1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Putnam, E. A., Park, E.-S., Aalfs, C. M., Hennekam, R. C. M., Milewicz, D. M.
|
|
<strong>Parental somatic and germ-line mosaicism for a FBN2 mutation and analysis of FBN2 transcript levels in dermal fibroblasts.</strong>
|
|
Am. J. Hum. Genet. 60: 818-827, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9106527/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9106527</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9106527" 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="9" class="mim-anchor"></a>
|
|
<a id="Putnam1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Putnam, E. A., Zhang, H., Ramirez, F., Milewicz, D. M.
|
|
<strong>Fibrillin-2 (FBN2) mutations result in the Marfan-like disorder, congenital contractural arachnodactyly.</strong>
|
|
Nature Genet. 11: 456-458, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7493032/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7493032</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7493032" 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/ng1295-456" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Quondamatteo2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Quondamatteo, F., Reinhardt, D. P., Charbonneau, N. L., Pophal, G., Sakai, L. Y., Herken, R.
|
|
<strong>Fibrillin-1 and fibrillin-2 in human embryonic and early fetal development.</strong>
|
|
Matrix Biol. 21: 637-646, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12524050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12524050</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12524050" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0945-053x(02)00100-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Ratnapriya2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ratnapriya, R., Zhan, X., Fariss, R. N., Branham, K. E., Zipprer, D., Chakarova, C. F., Sergeev, Y. V., Campos, M. M., Othman, M., Friedman, J. S., Maminishkis, A., Waseem, N. H., and 55 others.
|
|
<strong>Rare and common variants in extracellular matrix gene fibrillin 2 (FBN2) are associated with macular degeneration.</strong>
|
|
Hum. Molec. Genet. 23: 5827-5837, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24899048/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24899048</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24899048[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=24899048" 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/ddu276" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Sampson2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sampson, M. G., Coughlin, C. R., II., Kaplan, P., Conlin, L. K., Meyers, K. E. C., Zackai, E. H., Spinner, N. B., Copelovitch, L.
|
|
<strong>Evidence for a recurrent microdeletion at chromosome 16p11.2 associated with congenital anomalies of the kidney and urinary tract (CAKUT) and Hirschsprung disease.</strong>
|
|
Am. J. Med. Genet. 152A: 2618-2622, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20799338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20799338</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20799338" 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.33628" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Trask1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Trask, T. M., Ritty, T. M., Broekelmann, T., Tisdale, C., Mecham, R. P.
|
|
<strong>N-terminal domains of fibrillin 1 and fibrillin 2 direct the formation of homodimers: a possible first step in microfibril assembly.</strong>
|
|
Biochem. J. 340: 693-701, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10359653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10359653</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10359653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Wang1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, M., Clericuzio, C. L., Godfrey, M.
|
|
<strong>Familial occurrence of typical and severe lethal congenital contractural arachnodactyly caused by missplicing of exon 34 of fibrillin-2.</strong>
|
|
Am. J. Hum. Genet. 59: 1027-1034, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900230</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8900230" 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="15" class="mim-anchor"></a>
|
|
<a id="Wang1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, M., Price, C. E., Han, J., Cisler, J., Imaizumi, K., Van Thienen, M. N., DePaepe, A., Godfrey, M.
|
|
<strong>Recurrent mis-splicing of fibrillin exon 32 in two patients with neonatal Marfan syndrome.</strong>
|
|
Hum. Molec. Genet. 4: 607-613, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7633409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7633409</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7633409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/4.4.607" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Wang1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, M., Tsipouras, P., Godfrey, M.
|
|
<strong>Fibrillin-2 (FBN2) mutation in congenital contractural arachnodactyly. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 57: A231, 1995.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Zhang1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhang, H., Apfelroth, S. D., Hu, W., Davis, E. C., Sanguineti, C., Bonadio, J., Mecham, R. P., Ramirez, F.
|
|
<strong>Structure and expression of fibrillin-2, a novel microfibrillar component preferentially located in elastic matrices.</strong>
|
|
J. Cell Biol. 124: 855-863, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8120105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8120105</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8120105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1083/jcb.124.5.855" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Zhang1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhang, H., Hu, W., Ramirez, F.
|
|
<strong>Developmental expression of fibrillin genes suggests heterogeneity of extracellular microfibrils.</strong>
|
|
J. Cell Biol. 129: 1165-1176, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7744963/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7744963</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7744963" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1083/jcb.129.4.1165" 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">
|
|
Marla J. F. O'Neill - updated : 12/3/2014
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 11/22/2010<br>Patricia A. Hartz - updated : 2/13/2009
|
|
</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">
|
|
Carol A. Bocchini : 2/2/2009
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 02/14/2024
|
|
</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 : 07/13/2023<br>carol : 03/08/2022<br>carol : 03/07/2022<br>carol : 02/29/2016<br>carol : 12/4/2014<br>mcolton : 12/3/2014<br>carol : 2/19/2014<br>alopez : 7/24/2013<br>alopez : 6/13/2012<br>joanna : 6/12/2012<br>alopez : 6/11/2012<br>wwang : 12/22/2010<br>ckniffin : 11/22/2010<br>mgross : 2/17/2009<br>mgross : 2/17/2009<br>terry : 2/13/2009<br>carol : 2/4/2009<br>carol : 2/2/2009<br>carol : 2/2/2009
|
|
</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> 612570
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
FIBRILLIN 2; FBN2
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: FBN2</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 205821003;
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 5q23.3
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 5:128,257,909-128,538,245 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
5q23.3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Contractural arachnodactyly, congenital
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
121050
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Macular degeneration, early-onset
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
616118
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>While investigating the role of fibrillin-1 gene (FBN1; 134797) in the etiology of Marfan syndrome (154700), Lee et al. (1991) isolated a partial cDNA for fibrillin-2. </p><p>Using the partial FBN2 cDNA isolated by Lee et al. (1991) to screen an MG-63 human osteosarcoma cell line cDNA library, Zhang et al. (1994) obtained a full-length FBN2 clone. The deduced 2,889-amino acid protein contains an N-terminal signal peptide, followed by a proline-rich region, 3 tandem N-terminal EGF (131530)-like repeats, and 41 calcium-binding EGF-like repeats interspersed with another EGF-like repeat, a glycine-rich region, 7 TGF (see 190180)-binding protein repeats, and 2 Fib motifs. FBN2 also has 2 potential cell attachment sequences, multiple N-glycosylation sites, and 2 C-terminal polylysine stretches. The structures of FBN2 and FBN1 are highly similar, with the most significant difference being the glycine-rich sequence near the N terminus of FBN2, where FBN1 has a proline-rich sequence. FBN2 also contains 2 RGD motifs, whereas FBN1 has only 1. Northern blot analysis detected a 10- to 11-kb FBN2 transcript in MG-63 cells. Western blot analysis detected FBN2 at an apparent molecular mass of 350 kD. Immunohistochemical analysis of human fetal tissues showed colocalization of FBN1 with FBN2 in elastic and nonelastic connective tissues, with preferential accumulation of FBN2 in elastic fiber-rich matrices. </p><p>Zhang et al. (1995) cloned mouse Fbn2, which encodes a deduced 2,907-amino acid protein that shares 97% identity with human FBN2. </p><p>Using immunohistochemical analysis, Quondamatteo et al. (2002) investigated the distribution of FIB1 and FIB2 in human embryonic and early fetal tissues between gestational weeks 5 and 12. Both fibrillins were widely distributed. In most embryonic and early fetal organs, such as skin, lung, heart, aorta, central nervous system anlage, nerves, and ganglia, both fibrillins followed the same temporo-spatial pattern of distribution. However, in kidney, liver, rib anlagen, and notochord, distribution of FIB1 and FIB2 differed. </p><p>Ratnapriya et al. (2014) analyzed RNA sequencing (RNA-Seq) expression data from human fetal tissues and observed high levels of FBN2 transcripts in retinal pigment epithelium and choroid but not in retina. Immunostaining in human fetal eyes showed abundant FBN2 in Bruch membrane, choroid, and sclera. Similar FBN2 expression was obtained in the young adult monkey eye, although labeling was less intense. In contrast to human fetal eyes, FBN2 immunostaining was significantly reduced in choroid and sclera of human donors over 75 years of age, and was undetectable in Bruch membrane. Colabeling studies suggested that FBN2 is localized to the central elastin layer of the Bruch membrane. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Lee et al. (1991) mapped the FBN2 gene to chromosome 5q23-q31 by in situ hybridization. </p><p>By analysis of mouse/hamster somatic hybrid cell lines, Li et al. (1993) mapped the mouse Fbn2 gene to chromosome 18. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Zhang et al. (1994) demonstrated differences of expression of fibrillin-1 and fibrillin-2 in human ear cartilage. They noted that this may account for the abnormally shaped (i.e., crumpled) auricular helices that are a hallmark of congenital contractural arachnodactyly (CCA, DA9; 121050). </p><p>Using in situ hybridization and immunohistochemical analysis, Zhang et al. (1995) showed that Fib1 and Fib2 were differentially expressed in a temporal and spatial manner during mouse and rat development. In the majority of cases, Fib2 transcripts appeared earlier and accumulated for a shorter period of time than Fib1 transcripts. Synthesis of Fib1 correlated with late morphogenesis and the appearance of well-defined organ structures. Conversely, Fib2 synthesis coincided with early morphogenesis and the beginning of elastogenesis. Zhang et al. (1995) proposed that FIB1 provides mostly force-bearing structural support, whereas FIB2 predominantly regulates the early process of elastic fiber assembly. </p><p>Trask et al. (1999) found that human FIB1 and FIB2 homodimerized via an N-terminal region and that the interaction was stabilized by disulfide bonds. Dimer formation occurred intracellularly, suggesting that the process of fibrillin aggregation initiates early after biosynthesis of the molecules. No heterodimers of FIB1 and FIB2 were observed, suggesting that the pro- and gly-rich domains of FIB1 and FIB2, respectively, determine the specificity of dimer formation. </p><p>Lin et al. (2002) showed that the N terminus of human FIB1 could assemble in a linear fashion with the C terminus of another FIB1 molecule to form homotypic FIB1 microfibrils in the presence of calcium. FIB1 could interact similarly with FIB2 to form heterotypic microfibrils, but FIB2 N- and C-terminal constructs showed no significant interaction with one another. In dermal fibroblasts from a 1-year-old donor, both FIB1 and FIB2 were detected in a microfibrillar network. In contrast, osteoblasts from a 42-year-old donor showed a microfibrillar network made up of FIB1 alone. Lin et al. (2002) concluded that FIB1 can form microfibrillar structures in the absence of FIB2, and that FIB2 can occur in microfibrils with FIB1. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Congenital Contractural Arachnodactyly</em></strong></p><p>
|
|
Putnam and Milewicz (1995) and Wang et al. (1995) identified heterozygous point mutations in the FBN2 gene in cases of congenital contractural arachnodactyly (CCA; 121050). A mutation in a calcium-binding EGF-like motif (612570.0001) was found by the first authors and a mutation in a TGF-binding protein-like motif (612570.0002) by the second group.</p><p>In 2 patients with CCA, Putnam et al. (1995) identified 2 heterozygous missense mutations in FBN2 that caused substitutions of distinct cysteine residues in separate EGF-like repeats. In addition, Putnam et al. (1995) identified a G-to-A transition at nucleotide 2890 resulting in a val-to-ile change at amino acid 964 (V964I). They found the V964I change to be a common polymorphism with a heterozygosity index of 0.3. </p><p><strong><em>Early-Onset Macular Degeneration</em></strong></p><p>
|
|
In a father and 4 sons with early-onset macular degeneration (EOMD; 616118), Ratnapriya et al. (2014) identified heterozygosity for a missense mutation in the FBN2 gene (E1144K; 612570.0011). Analysis of 96 additional patients with EOMD as well as 96 patients with age-related macular degeneration (ARMD; see 603075) revealed 2 nonsynonymous rare variants, one in an EOMD patient (M1247T; 612570.0012) and another in a patient with ARMD. Ratnapriya et al. (2014) also detected suggestive association of a common FBN2 nonsynonymous variant (V965I; rs154001) with ARMD (odds ratio, 1.10; p = 3.79 x 10(-5)). The authors concluded that rare and common variants in FBN2 contribute to both mendelian and complex forms of macular degeneration. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>12 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FBN2, CYS1252TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852825,
|
|
|
|
|
|
|
|
ClinVar: RCV000000548
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with congenital contractural arachnodactyly (CCA; 121050), Putnam and Milewicz (1995) found a heterozygous G-to-A transition at nucleotide 3755 of their FBN2 cDNA that changed the cysteine at residue 1252 to a tyrosine (C1252Y). This altered one of the highly conserved cysteines in an epidermal growth factor-like domain of the fibrillin-2 protein. By analogy, many of the missense mutations found in FBN1 that result in the Marfan syndrome affect conserved cysteines in the EGF-like domains of the fibrillin-1 protein. The C1252Y mutation altered a restriction enzyme recognition sequence which they used to screen unrelated individuals for the nucleotide substitution; 106 chromosomes failed to show the alteration.</p><p>By SSCP analysis followed by direct sequencing, Putnam et al. (1995) identified the C1252Y mutation in 1 of 11 unrelated CCA patients. The mutation was absent in 43 unrelated control individuals and in the other 10 patients. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FBN2, GLU390LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852826,
|
|
|
|
|
|
|
|
ClinVar: RCV000000549
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with congenital contractural arachnodactyly (CCA; 121050), Wang et al. (1995) found a heterozygous G-to-A transition causing an E390K substitution in a transforming growth factor binding protein-like repeat. This domain is equivalent to exon 9 in the B region of FBN1. This position, in both FBN1 and FBN2, is normally occupied by a negatively charged acidic amino acid, aspartic acid, and glutamic acid, respectively. The authors speculated that the substitution of a glutamic acid by a basic and positively charged lysine could significantly alter the structure of the domain and affect higher order microfibrillar structure.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 REMOVED FROM DATABASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FBN2, IVS33, A-T, -2
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776518,
|
|
|
|
|
|
|
|
ClinVar: RCV000000551
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Wang et al. (1996) described a mother and daughter with classic and severe lethal congenital contractural arachnodactyly (CCA; 121050), respectively. The FBN2 mutation resulted in the identical missplicing of exon 34 in both patients. Significantly, the mother was somatic mosaic for the mutation, thus explaining her milder phenotype. The mutation consisted of an A-to-T transversion at the -2 position of the consensus acceptor splice site, changing AG to TG at the 3-prime end of intron 33. The mother had been born with congenital contractures of the hands, elbows, and knees. Elbow and knee contractures improved spontaneously, and in childhood she underwent surgical release of finger contractures. In adolescence, mitral valve prolapse was recognized. At the age of 24 years, she delivered a premature daughter who was recognized as having CCA on the first day of life. Pregnancy was complicated by a third-trimester polyhydramnios and spontaneous delivery at 34 weeks of gestation. She was diagnosed with type-B interrupted aortic arch with large ventricular septal defect and moderate atrial septal defect, duodenal atresia and intestinal malrotation, single umbilical artery, vertebral anomalies, and arachnodactyly with contractures of elbows and knees. Both ears showed a crumpled irregular superior helix and prominent antihelix and root of the helix. There was pectus excavatum. Duodenal atresia was repaired on day 3, interrupted aortic arch was repaired at 1 month of age, and gastrostomy tube was placed for gastroesophageal reflux requiring subsequent jejunostomy because of gastric perforation, at the age of 1.5 months. The infant experienced multiple episodes of sepsis and died at the age of 9 months. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FBN2, IVS28, A-G, -15
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776519,
|
|
|
|
|
|
|
|
ClinVar: RCV000000552
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a clinically unaffected man with 2 children with congenital contractural arachnodactyly (CCA; 121050), Putnam et al. (1997) found mosaicism for a heterozygous exon splicing error deleting nucleotides 3722 to 3844 of the FBN2 mRNA. This cDNA deletion resulted in selective removal of 1 of the 43 calcium-binding EGF-like domains of the fibrillin-2 protein. Analysis of genomic DNA indicated that the splicing error resulted from an A-to-G transition 15 nucleotides upstream from 3-prime splice site of the intron. The genomic mutation resulting in the splicing error altered a putative branch point sequence important for lariat formation, an intermediate structure of normal splicing. The mutation was detectable in DNA from the father's hair bulbs and buccal cells but not his white blood cell DNA, indicating that the father was a somatic mosaic. Analysis of transcript levels by use of dermal fibroblasts from the proband demonstrated that the FBN2 allele containing the exon deletion was expressed at a higher level than the allele inherited from the mother. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FBN2, IVS30, T-G, -26
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2126895611,
|
|
|
|
|
|
|
|
ClinVar: RCV000000553
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 5-generation family in which 18 individuals had congenital contractural arachnodactyly (CCA; 121050), Maslen et al. (1997) found partial skipping of exon 31 of the FBN2 gene in affected individuals. Approximately 25% mutant transcript was produced, which was apparently sufficient to cause a CCA phenotype. Sequence analysis of genomic DNA revealed an unusual base composition for intron 30 and identified a t-to-g transversion at position -26, in the vicinity of the splicing branch-point site in intron 30. This was the first report of a CCA mutation in a multiplex family, unequivocally establishing that mutations in FBN2 are responsible for the CCA phenotype. Branch-point mutations had only rarely been associated with human disease (e.g., 600509.0005). Maslen et al. (1997) pointed out that deletion in exon 31 of the FBN1 gene results in the severe neonatal Marfan syndrome (134797.0019) and a recurrent missplicing of exon 32 (134797.0020) has been observed in 2 unrelated cases of neonatal Marfan syndrome (Wang et al., 1995). It is of note, therefore, that deletion of a corresponding exon in FBN2 is associated with a mild phenotype. The family studied by Maslen et al. (1997) lived in Switzerland. Affected individuals could be identified immediately by their mothers at birth, on the basis of the hands, which were in a clenched (fist-like) position, and on the basis of their ears, which unequivocally were described as resembling 'cabbage leaves.' The auricular deformity resolved with age and was inconspicuous in all affected adults. Camptodactyly also improved with age, but remained the leading phenotypic feature. Contractures of larger joints were present in varying degrees in all affected individuals. Furthermore, all showed kyphoscoliosis, thoracic deformities, and muscular hypoplasia of calves and forearms. All affected individuals had dolichostenomelia and arachnodactyly. In most, arm span significantly exceeded body height but the discrepancy was underestimated because of contractures of elbows and fingers. This same underestimation occurred in assessment of the lower-body segment, as a result of contractures of the knees. Marked truncal adiposity was present in affected females, which contrasted with the long and slender limbs. Two patients, related as first cousins, had undergone surgery for habitual patella luxation and another affected member was observed to have elevated and hypermobile patellas. Most of the affected family members were noted to have fine and thin skin, and supragluteal striae were noted in 3 patients. No cardiovascular abnormalities were detected in any of the affected family members and there was no history or sign of lens dislocation or retinal detachment. A phenotypically particularly instructive pair of dizygotic male twins were pictured. In contrast to the unaffected twin, dolichostenomelia, arachnodactyly, pectus carinatum, hypoplastic calf muscles, elevation of the patella, and a characteristic deformity of the ear were evident. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FBN2, ASP1114HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852827,
|
|
|
|
|
|
|
|
ClinVar: RCV000000554
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family in which members over 4 generations had signs and symptoms associated with congenital contractural arachnodactyly (CCA; 121050), Babcock et al. (1998) identified a heterozygous G-to-C transversion at nucleotide 3340 of the FBN2 gene. The 3340G-C mutation predicted an asp1114-to-his substitution and also altered the 5-prime donor splice site consensus sequence of exon 25. RT-PCR and DNA sequence analyses demonstrated that this missense mutation also caused low level in-frame missplicing of exon 25 with partial skipping of that exon. Consequently, this single point mutation produced a heterogeneous population of mutant fibrillin-2 molecules in a single individual. Despite the complex manifestation of the mutation, it was associated with a relatively mild phenotype. Analysis of FBN2 allele expression in cultured dermal fibroblasts derived from the proband showed that the mutant allele was preferentially expressed, contributing about 84% of the total transcript. This indicates that an overabundance of mutant transcript does not necessarily correlate with a more severe CCA phenotype. The proband was a 67-year-old woman who was 168 cm tall. Pertinent history included bilaterally dislocating patellae during childhood, chronic aches and pains in numerous joints, muscles, and tendons, and tight hamstrings throughout life. Physical examination showed dental crowding, positive wrist sign of Marfan syndrome, mild thoracic scoliosis, long halluces, tight finger joints, straight elbows, genu valgum, and underdeveloped calf muscles. The external ears were abnormal with an extra piece of cartilage present. Eye findings included myopia and astigmatism. Three daughters were similarly affected. The 39-year-old daughter was 168 cm tall and a had a history of orthopedic problems since birth, including hyperextended feet at birth, contractures of elbows, limited movement in hips, dislocated patellae treated surgically, slight scoliosis, and metatarsus varus. She also had stretch marks on her thighs and an extra piece of cartilage in the external ears. Eye findings included myopia with astigmatism. The 5-year-old son of this woman was thin and tall and had metatarsus varus, contractures of the knees, and the same external ear abnormality. The 37-year-old daughter of the proband was 170 cm tall. She had a history of scoliosis and spinal fusion surgery at age 12 years, dislocated patellae treated surgically, metatarsus varus, thin legs, and contractures of the elbows. On examination, positive thumb sign, positive wrist sign, and long halluces were also noted. She had the same unusual external ears and myopia with astigmatism as did her mother and sister. The 35-year-old daughter of the proband was 173 cm tall and had a history of metatarsus varus, contractures of the elbows, limited hip rotation, and mild myopia. No affected members of this family had abnormal cardiovascular findings. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FBN2, CYS1141PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852828,
|
|
|
|
|
|
gnomAD: rs137852828,
|
|
|
|
|
|
ClinVar: RCV000000555
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a French Canadian girl with typical features of congenital contractural arachnodactyly (CCA; 121050), Belleh et al. (2000) identified a heterozygous 3422G-T transversion in exon 26 of the FBN2 gene, resulting in a cys1141-to-phe (C1141F) amino acid substitution. Neither parent carried the mutation. The pinnae were 'crumpled,' and there was midthoracic kyphoscoliosis. There was restriction to the extension of the thumbs at the metacarpophalangeal joint. The extension at the distal interphalangeal joints of the first to fourth fingers was also limited bilaterally. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FBN2, CYS1252TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28931602,
|
|
|
|
|
|
|
|
ClinVar: RCV000000556
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Belleh et al. (2000) described a teenaged girl with features of congenital contractural arachnodactyly (CCA; 121050): tall stature, slender body habitus, arachnodactyly, camptodactyly, and progressive kyphoscoliosis. She had mild mental retardation and mild spasticity. Contractures of the fingers were present. As in the other patient reported by Belleh et al. (2000) (see 612570.0008), the legs were slender with reduced muscle mass, particularly in the calves. Belleh et al. (2000) identified a heterozygous 3756T-G transversion in exon 29 of the FBN2 gene, resulting in a cys1252-to-trp (C1252W) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 CONTRACTURAL ARACHNODACTYLY, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FBN2, ASN1259LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606802,
|
|
|
|
|
|
|
|
ClinVar: RCV000000557
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with congenital contractural arachnodactyly (CCA; 121050), Sampson et al. (2010) identified a heterozygous 3777T-A transversion in the FBN2 gene, resulting in an asn1259-to-lys (N1259K) substitution in a conserved residue in the calcium-binding EGF-like domain 15. He had congenital contractures of the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of the fingers and toes, contractures of the elbows, mild crumpling of the ear helices without ear pits or tags, and right intraabdominal testis. The patient's father, paternal grandmother, and a paternal cousin were reported to have contractures, but DNA samples from these individuals were not available. In addition to congenital contractures, the patient was also found to have short-segment Hirschsprung disease, pervasive developmental disorder, auditory processing difficulties, and attention deficit-hyperactivity disorder. Genomewide SNP array identified an extended 1.7-Mb deletion at chromosome 16p11.2 (see 613444), which the authors postulated was related to the gastrointestinal abnormality. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MACULAR DEGENERATION, EARLY-ONSET</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FBN2, GLU1144LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs200060005,
|
|
|
|
|
|
gnomAD: rs200060005,
|
|
|
|
|
|
ClinVar: RCV000148948, RCV000468154, RCV000680529, RCV002311021, RCV003313043
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a father and 4 sons with early-onset macular degeneration (EOMD; 616118), Ratnapriya et al. (2014) identified heterozygosity for a c.3430G-A transition in the FBN2 gene, resulting in a glu1144-to-lys (E1144K) substitution within the twelfth Ca(2+)-EGF-like domain. The mutation was not found in an unaffected daughter and son. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 MACULAR DEGENERATION, EARLY-ONSET</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FBN2, MET1247THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs149054177,
|
|
|
|
|
|
gnomAD: rs149054177,
|
|
|
|
|
|
ClinVar: RCV000148949, RCV000693997, RCV002345459, RCV004700475
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with early-onset macular degeneration (EOMD; 616118), Ratnapriya et al. (2014) identified heterozygosity for a c.3740T-C transition in the FBN2 gene, resulting in a met1247-to-thr (M1247T) substitution within the fifteenth Ca(2+)-EGF-like domain. The variant was not present in 4,300 exomes in the NHLBI Exome Variant Server database. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Babcock, D., Gasner, C., Francke, U., Maslen, C.
|
|
<strong>A single mutation that results in an asp-to-his substitution and partial exon skipping in a family with congenital contractual arachnodactyly.</strong>
|
|
Hum. Genet. 103: 22-28, 1998.
|
|
|
|
|
|
[PubMed: 9737771]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050777]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Belleh, S., Zhou, G., Wang, M., Der Kaloustian, V. M., Pagon, R. A., Godfrey, M.
|
|
<strong>Two novel fibrillin-2 mutations in congenital contractural arachnodactyly.</strong>
|
|
Am. J. Med. Genet. 92: 7-12, 2000.
|
|
|
|
|
|
[PubMed: 10797416]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lee, B., Godfrey, M., Vitale, E., Hori, H., Mattei, M.-G., Sarfarazi, M., Tsipouras, P., Ramirez, F., Hollister, D. W.
|
|
<strong>Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes.</strong>
|
|
Nature 352: 330-334, 1991.
|
|
|
|
|
|
[PubMed: 1852206]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/352330a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, X., Pereira, L., Zhang, H., Sanguineti, C., Ramirez, F., Bonadio, J., Francke, U.
|
|
<strong>Fibrillin genes map to regions of conserved mouse/human synteny on mouse chromosomes 2 and 18.</strong>
|
|
Genomics 18: 667-672, 1993.
|
|
|
|
|
|
[PubMed: 8307578]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0888-7543(05)80371-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lin, G., Tiedemann, K., Vollbrandt, T., Peters, H., Batge, B., Brinckmann, J., Reinhardt, D. P.
|
|
<strong>Homo- and heterotypic fibrillin-1 and -2 interactions constitute the basis for the assembly of microfibrils.</strong>
|
|
J. Biol. Chem. 277: 50795-50804, 2002.
|
|
|
|
|
|
[PubMed: 12399449]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M210611200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maslen, C., Babcock, D., Raghunath, M., Steinmann, B.
|
|
<strong>A rare branch-point mutation is associated with missplicing of fibrillin-2 in a large family with congenital contractural arachnodactyly.</strong>
|
|
Am. J. Hum. Genet. 60: 1389-1398, 1997.
|
|
|
|
|
|
[PubMed: 9199560]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/515472]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Putnam, E. A., Milewicz, D. M.
|
|
<strong>A mutation in the FBN2 gene in dermal fibroblasts from a congenital contractural arachnodactyly patient. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 57: A225, 1995.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Putnam, E. A., Park, E.-S., Aalfs, C. M., Hennekam, R. C. M., Milewicz, D. M.
|
|
<strong>Parental somatic and germ-line mosaicism for a FBN2 mutation and analysis of FBN2 transcript levels in dermal fibroblasts.</strong>
|
|
Am. J. Hum. Genet. 60: 818-827, 1997.
|
|
|
|
|
|
[PubMed: 9106527]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Putnam, E. A., Zhang, H., Ramirez, F., Milewicz, D. M.
|
|
<strong>Fibrillin-2 (FBN2) mutations result in the Marfan-like disorder, congenital contractural arachnodactyly.</strong>
|
|
Nature Genet. 11: 456-458, 1995.
|
|
|
|
|
|
[PubMed: 7493032]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1295-456]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Quondamatteo, F., Reinhardt, D. P., Charbonneau, N. L., Pophal, G., Sakai, L. Y., Herken, R.
|
|
<strong>Fibrillin-1 and fibrillin-2 in human embryonic and early fetal development.</strong>
|
|
Matrix Biol. 21: 637-646, 2002.
|
|
|
|
|
|
[PubMed: 12524050]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0945-053x(02)00100-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ratnapriya, R., Zhan, X., Fariss, R. N., Branham, K. E., Zipprer, D., Chakarova, C. F., Sergeev, Y. V., Campos, M. M., Othman, M., Friedman, J. S., Maminishkis, A., Waseem, N. H., and 55 others.
|
|
<strong>Rare and common variants in extracellular matrix gene fibrillin 2 (FBN2) are associated with macular degeneration.</strong>
|
|
Hum. Molec. Genet. 23: 5827-5837, 2014.
|
|
|
|
|
|
[PubMed: 24899048]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddu276]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sampson, M. G., Coughlin, C. R., II., Kaplan, P., Conlin, L. K., Meyers, K. E. C., Zackai, E. H., Spinner, N. B., Copelovitch, L.
|
|
<strong>Evidence for a recurrent microdeletion at chromosome 16p11.2 associated with congenital anomalies of the kidney and urinary tract (CAKUT) and Hirschsprung disease.</strong>
|
|
Am. J. Med. Genet. 152A: 2618-2622, 2010.
|
|
|
|
|
|
[PubMed: 20799338]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.33628]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Trask, T. M., Ritty, T. M., Broekelmann, T., Tisdale, C., Mecham, R. P.
|
|
<strong>N-terminal domains of fibrillin 1 and fibrillin 2 direct the formation of homodimers: a possible first step in microfibril assembly.</strong>
|
|
Biochem. J. 340: 693-701, 1999.
|
|
|
|
|
|
[PubMed: 10359653]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, M., Clericuzio, C. L., Godfrey, M.
|
|
<strong>Familial occurrence of typical and severe lethal congenital contractural arachnodactyly caused by missplicing of exon 34 of fibrillin-2.</strong>
|
|
Am. J. Hum. Genet. 59: 1027-1034, 1996.
|
|
|
|
|
|
[PubMed: 8900230]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, M., Price, C. E., Han, J., Cisler, J., Imaizumi, K., Van Thienen, M. N., DePaepe, A., Godfrey, M.
|
|
<strong>Recurrent mis-splicing of fibrillin exon 32 in two patients with neonatal Marfan syndrome.</strong>
|
|
Hum. Molec. Genet. 4: 607-613, 1995.
|
|
|
|
|
|
[PubMed: 7633409]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.4.607]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, M., Tsipouras, P., Godfrey, M.
|
|
<strong>Fibrillin-2 (FBN2) mutation in congenital contractural arachnodactyly. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 57: A231, 1995.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, H., Apfelroth, S. D., Hu, W., Davis, E. C., Sanguineti, C., Bonadio, J., Mecham, R. P., Ramirez, F.
|
|
<strong>Structure and expression of fibrillin-2, a novel microfibrillar component preferentially located in elastic matrices.</strong>
|
|
J. Cell Biol. 124: 855-863, 1994.
|
|
|
|
|
|
[PubMed: 8120105]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1083/jcb.124.5.855]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, H., Hu, W., Ramirez, F.
|
|
<strong>Developmental expression of fibrillin genes suggests heterogeneity of extracellular microfibrils.</strong>
|
|
J. Cell Biol. 129: 1165-1176, 1995.
|
|
|
|
|
|
[PubMed: 7744963]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1083/jcb.129.4.1165]
|
|
|
|
|
|
</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">
|
|
Marla J. F. O'Neill - updated : 12/3/2014<br>Cassandra L. Kniffin - updated : 11/22/2010<br>Patricia A. Hartz - updated : 2/13/2009
|
|
</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">
|
|
Carol A. Bocchini : 2/2/2009
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 02/14/2024<br>carol : 07/13/2023<br>carol : 03/08/2022<br>carol : 03/07/2022<br>carol : 02/29/2016<br>carol : 12/4/2014<br>mcolton : 12/3/2014<br>carol : 2/19/2014<br>alopez : 7/24/2013<br>alopez : 6/13/2012<br>joanna : 6/12/2012<br>alopez : 6/11/2012<br>wwang : 12/22/2010<br>ckniffin : 11/22/2010<br>mgross : 2/17/2009<br>mgross : 2/17/2009<br>terry : 2/13/2009<br>carol : 2/4/2009<br>carol : 2/2/2009<br>carol : 2/2/2009
|
|
</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>
|
|
|
|
|