12020 lines
1.3 MiB
12020 lines
1.3 MiB
|
|
|
|
|
|
|
|
|
|
<!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
|
|
|
|
- *134934 - FIBROBLAST GROWTH FACTOR RECEPTOR 3; FGFR3
|
|
|
|
|
|
- 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=134934"><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">*134934</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/134934">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=ENSG00000068078;t=ENST00000440486" 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=2261" 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=134934" 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=ENSG00000068078;t=ENST00000440486" 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_000142,NM_001163213,NM_001354809,NM_001354810,NM_022965,NR_148971,XM_006713868,XM_006713869,XM_006713870,XM_006713871,XM_006713873,XM_011513420,XM_011513422,XM_047449820,XM_047449821,XM_047449822,XM_047449823,XM_047449824" 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_000142" 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=134934" 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=00624&isoform_id=00624_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/FGFR3" 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/120050,182565,182569,186623,695549,841314,914202,1922308,4503711,7533125,9719332,13112048,14161388,14161390,14161392,20452380,20452381,53689008,62088462,113197970,119602968,119602969,119602970,119602971,119602972,119602973,119602974,124504641,157743183,254028242,305678515,578808120,578808122,578808124,578808126,578808130,608785275,608785555,608785614,767929030,767929032,1236498658,1237937822,1354531435,1354531437,1768406746,2217349483,2217349487,2217349492,2217349495,2217349497,2462595619,2462595621,2462595623,2462595625,2462595627,2462595629,2462595631,2462595633" 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/P22607" 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=2261" 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=ENSG00000068078;t=ENST00000440486" 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=FGFR3" 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=FGFR3" 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+2261" 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/FGFR3" 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:2261" 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/2261" 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=chr4&hgg_gene=ENST00000440486.8&hgg_start=1793293&hgg_end=1808867&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:3690" 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:3690" 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=134934[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=134934[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/FGFR3/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/ENSG00000068078" 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=FGFR3" 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=FGFR3" 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=FGFR3" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=FGFR3&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/PA28129" 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:3690" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://flybase.org/reports/FBgn0010389.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:95524" 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/FGFR3#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:95524" 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/2261/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://omia.org/OMIA001703/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=2261" 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=WBGene00001184;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-000816-1" 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="mimCellLines">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cell Lines</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:134934" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</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:2261" 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=FGFR3&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> 205468002, 389157002, 389158007, 440350001, 702361006, 720601000, 787407003, 83015004, 86268005<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> Q77.4<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>
|
|
134934
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
FIBROBLAST GROWTH FACTOR RECEPTOR 3; FGFR3
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="includedTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
FGFR3/TACC3 FUSION GENE, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=FGFR3" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">FGFR3</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/4/34?start=-3&limit=10&highlight=34">4p16.3</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr4:1793293-1808867&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'})">4:1,793,293-1,808,867</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=100800,109800,610474,603956,114500,612247,146000,620192,602849,162900,616482,273300,187600,187601" 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="14">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/4/34?start=-3&limit=10&highlight=34">
|
|
4p16.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Achondroplasia
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/100800"> 100800 </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">
|
|
Bladder cancer, somatic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/109800"> 109800 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
CATSHL syndrome
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/610474"> 610474 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Cervical cancer, somatic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/603956"> 603956 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Colorectal cancer, somatic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/114500"> 114500 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Crouzon syndrome with acanthosis nigricans
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/612247"> 612247 </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">
|
|
Hypochondroplasia
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/146000"> 146000 </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">
|
|
LADD syndrome 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/620192"> 620192 </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">
|
|
Muenke syndrome
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/602849"> 602849 </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">
|
|
Nevus, epidermal, somatic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/162900"> 162900 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
SADDAN
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/616482"> 616482 </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">
|
|
Spermatocytic seminoma, somatic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/273300"> 273300 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Thanatophoric dysplasia, type I
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/187600"> 187600 </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">
|
|
Thanatophoric dysplasia, type II
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/187601"> 187601 </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/134934" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/134934" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>Fibroblast growth factors (FGFs; see <a href="/entry/131220">131220</a>) are a family of polypeptide growth factors involved in a variety of activities, including mitogenesis, angiogenesis, and wound healing. FGF receptors, such as FGFR3, contain an extracellular domain with either 2 or 3 immunoglobulin (Ig)-like domains, a transmembrane domain, and a cytoplasmic tyrosine kinase domain (summary by <a href="#53" class="mim-tip-reference" title="Keegan, K., Johnson, D. E., Williams, L. T., Hayman, M. J. <strong>Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3.</strong> Proc. Nat. Acad. Sci. 88: 1095-1099, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1847508/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1847508</a>] [<a href="https://doi.org/10.1073/pnas.88.4.1095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1847508">Keegan et al., 1991</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1847508" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>By screening a human K562 cell cDNA library for novel tyrosine kinase receptors, <a href="#53" class="mim-tip-reference" title="Keegan, K., Johnson, D. E., Williams, L. T., Hayman, M. J. <strong>Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3.</strong> Proc. Nat. Acad. Sci. 88: 1095-1099, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1847508/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1847508</a>] [<a href="https://doi.org/10.1073/pnas.88.4.1095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1847508">Keegan et al. (1991)</a> isolated a cDNA encoding FGFR3, which is highly homologous to previously described FGFRs. The deduced 806-amino acid protein has an N-terminal signal sequence, followed by 3 extracellular Ig-like domains, a transmembrane domain, and a split C-terminal cytoplasmic kinase domain. The kinase domain contains a GxGxxG motif and a conserved lysine, both of which are characteristic of ATP-binding motifs, and a DFGLAR motif conserved in tyrosine kinases. Northern blot analysis of K562 cells revealed a major transcript of 4.5 kb and a minor transcript of 7.0 kb. Expression of FGFR3 cDNA in COS cells directed formation of a 125-kD glycoprotein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1847508" 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="#122" class="mim-tip-reference" title="Thompson, L. M., Plummer, S., Schalling, M., Altherr, M. R., Gusella, J. F., Housman, D. E., Wasmuth, J. J. <strong>A gene encoding a fibroblast growth factor receptor isolated from the Huntington disease gene region of human chromosome 4.</strong> Genomics 11: 1133-1142, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1664411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1664411</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90041-c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1664411">Thompson et al. (1991)</a> isolated the FGFR3 gene from the Huntington disease (HD; <a href="/entry/143100">143100</a>) region on chromosome 4p16.3. Histochemical analysis using in situ hybridization showed that the FGFR3 gene was expressed in many areas of brain, including caudate and putamen. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1664411" 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="#85" class="mim-tip-reference" title="Perez-Castro, A. V., Wilson, J., Altherr, M. R. <strong>Genomic organization of the human fibroblast growth factor receptor 3 (FGFR3) gene and comparative sequence analysis with the mouse Fgfr3 gene.</strong> Genomics 41: 10-16, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9126476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9126476</a>] [<a href="https://doi.org/10.1006/geno.1997.4616" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9126476">Perez-Castro et al. (1997)</a> reported that the human and mouse FGFR3 amino acid sequences share 92% homology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9126476" 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="#104" class="mim-tip-reference" title="Scotet, E., Houssaint, E. <strong>The choice between alternative IIIb and IIIc exons of the FGFR-3 gene is not strictly tissue-specific.</strong> Biochim. Biophys. Acta 1264: 238-242, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7495869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7495869</a>] [<a href="https://doi.org/10.1016/0167-4781(95)00156-b" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7495869">Scotet and Houssaint (1995)</a> identified splice variants of FGFR3 that use 2 alternative exons, 3b and 3c, encoding the C-terminal half of Ig domain 3. They found that epithelial cells show exclusively the 3b transcripts, while fibroblastic cells show a mixture of 3b and 3c transcripts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7495869" 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="#106" class="mim-tip-reference" title="Shimizu, A., Tada, K., Shukunami, C., Hiraki, Y., Kurokawa, T., Magane, N., Kurokawa-Seo, M. <strong>A novel alternatively spliced fibroblast growth factor receptor 3 isoform lacking the acid box domain is expressed during chondrogenic differentiation of ATDC5 cells.</strong> J. Biol. Chem. 276: 11031-11040, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11134040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11134040</a>] [<a href="https://doi.org/10.1074/jbc.M003535200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11134040">Shimizu et al. (2001)</a> identified an Fgfr3 isoform in mouse that lacks the acid box region within the extracellular domain. PCR analysis showed that this variant, which the authors called delta-AB, was expressed in rat rib cartilage chondrocytes and in undifferentiated cultures of mouse chondroprogenitor cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11134040" 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="#51" class="mim-tip-reference" title="Jang, J.-H. <strong>Identification and characterization of soluble isoform of fibroblast growth factor receptor 3 in human SaOS-2 osteosarcoma cells.</strong> Biochem. Biophys. Res. Commun. 292: 378-382, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11906172/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11906172</a>] [<a href="https://doi.org/10.1006/bbrc.2002.6668" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11906172">Jang (2002)</a> identified a soluble variant of FGFR3 produced by skipping exons 8, 9, and 10 in a human osteosarcoma cell line. This splicing event leads to the generation of an mRNA encoding an FGFR3 protein in which the C-terminal portion of the Ig-like-3 domain and the transmembrane domain are deleted, while the remainder of the mature molecule is fused in-frame to the C-terminal cytoplasmic kinase domains. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11906172" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneStructure" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneStructureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneStructureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#85" class="mim-tip-reference" title="Perez-Castro, A. V., Wilson, J., Altherr, M. R. <strong>Genomic organization of the human fibroblast growth factor receptor 3 (FGFR3) gene and comparative sequence analysis with the mouse Fgfr3 gene.</strong> Genomics 41: 10-16, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9126476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9126476</a>] [<a href="https://doi.org/10.1006/geno.1997.4616" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9126476">Perez-Castro et al. (1997)</a> reported that the FGFR3 gene contains 19 exons spanning 16.5 kb. The overall structure and organization of the human FGFR3 gene is nearly identical to that of the mouse Fgfr3 gene. The 5-prime flanking region lacks the typical TATA or CAAT boxes. However, several putative binding sites for transcription factors SP1 (<a href="/entry/189906">189906</a>), AP2 (<a href="/entry/107580">107580</a>), KROX24 (<a href="/entry/128990">128990</a>), IgHC.4, and Zeste (see <a href="/entry/601674">601674</a>) are present. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9126476" 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="#122" class="mim-tip-reference" title="Thompson, L. M., Plummer, S., Schalling, M., Altherr, M. R., Gusella, J. F., Housman, D. E., Wasmuth, J. J. <strong>A gene encoding a fibroblast growth factor receptor isolated from the Huntington disease gene region of human chromosome 4.</strong> Genomics 11: 1133-1142, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1664411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1664411</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90041-c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1664411">Thompson et al. (1991)</a> mapped the FGFR3 gene to the HD region on chromosome 4p16.3. Using an interspecific backcross mapping panel, <a href="#4" class="mim-tip-reference" title="Avraham, K. B., Givol, D., Avivi, A., Yayon, A., Copeland, N. G., Jenkins, N. A. <strong>Mapping of murine fibroblast growth factor receptors refines regions of homology between mouse and human chromosomes.</strong> Genomics 21: 656-658, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7959747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7959747</a>] [<a href="https://doi.org/10.1006/geno.1994.1330" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7959747">Avraham et al. (1994)</a> mapped the Fgfr3 gene to mouse chromosome 5 in a region of homology of synteny with human chromosome 4. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1664411+7959747" 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="#53" class="mim-tip-reference" title="Keegan, K., Johnson, D. E., Williams, L. T., Hayman, M. J. <strong>Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3.</strong> Proc. Nat. Acad. Sci. 88: 1095-1099, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1847508/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1847508</a>] [<a href="https://doi.org/10.1073/pnas.88.4.1095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1847508">Keegan et al. (1991)</a> showed that human acidic and basic fibroblast growth factors activated FGFR3, as measured by calcium-ion efflux assays. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1847508" 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="#106" class="mim-tip-reference" title="Shimizu, A., Tada, K., Shukunami, C., Hiraki, Y., Kurokawa, T., Magane, N., Kurokawa-Seo, M. <strong>A novel alternatively spliced fibroblast growth factor receptor 3 isoform lacking the acid box domain is expressed during chondrogenic differentiation of ATDC5 cells.</strong> J. Biol. Chem. 276: 11031-11040, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11134040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11134040</a>] [<a href="https://doi.org/10.1074/jbc.M003535200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11134040">Shimizu et al. (2001)</a> found that, when stably transfected into a mouse pro-B cell line, mouse Fgfr3 preferentially mediated the mitogenic response to Fgf1 and showed a poor response to Fgf2. In contrast, the delta-AB isoform, which lacks the acid box, mediated a higher mitogenic response to Fgf2. The delta-AB isoform also required lower concentrations of heparin for activity than Fgfr3 did. <a href="#107" class="mim-tip-reference" title="Shimizu, A., Takashima, Y., Kurokawa-Seo, M. <strong>FGFR3 isoforms have distinct functions in the regulation of growth and cell morphology.</strong> Biochem. Biophys. Res. Commun. 290: 113-120, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11779141/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11779141</a>] [<a href="https://doi.org/10.1006/bbrc.2001.6190" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11779141">Shimizu et al. (2002)</a> found that Fgfr3 induced marked rounding of mouse chondroprogenitor cells, an effect that was not observed with the delta-AB isoform. Fgfr3 also induced complete growth arrest, whereas the delta-AB isoform induced only moderate growth inhibition. Biochemical assays indicated that Fgfr3 and delta-AB differed in their ability to utilize Stat1 (<a href="/entry/600555">600555</a>) pathways and signals involved in cell rounding. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11779141+11134040" 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="#51" class="mim-tip-reference" title="Jang, J.-H. <strong>Identification and characterization of soluble isoform of fibroblast growth factor receptor 3 in human SaOS-2 osteosarcoma cells.</strong> Biochem. Biophys. Res. Commun. 292: 378-382, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11906172/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11906172</a>] [<a href="https://doi.org/10.1006/bbrc.2002.6668" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11906172">Jang (2002)</a> found that, when expressed in insect cells, the secreted isoform of FGFR3 bound both FGF1 (<a href="/entry/131220">131220</a>) and FGF2 (<a href="/entry/134920">134920</a>), leading to loss of ligand-binding specificity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11906172" 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 a 3-dimensional cell culture model, <a href="#20" class="mim-tip-reference" title="Davidson, D., Blanc, A., Filion, D., Wang, H., Plut, P., Pfeffer, G., Buschmann, M. D., Henderson, J. E. <strong>Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis.</strong> J. Biol. Chem. 280: 20509-20515, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781473</a>] [<a href="https://doi.org/10.1074/jbc.M410148200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15781473">Davidson et al. (2005)</a> found that mesenchymal cells released from wildtype, but not Fgfr3 -/-, embryonic day-11.5 (E11.5) mouse limb buds condensed to form nodules and expressed molecular markers characteristic of cells of chondrogenic lineage. In low-density culture, both wildtype and Fgfr3 -/- mesenchymal cells differentiated in response to Fgf2, but only wildtype cells differentiated in response to Fgf18 (<a href="/entry/603726">603726</a>). <a href="#20" class="mim-tip-reference" title="Davidson, D., Blanc, A., Filion, D., Wang, H., Plut, P., Pfeffer, G., Buschmann, M. D., Henderson, J. E. <strong>Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis.</strong> J. Biol. Chem. 280: 20509-20515, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781473</a>] [<a href="https://doi.org/10.1074/jbc.M410148200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15781473">Davidson et al. (2005)</a> concluded that FGFR3 and FGF18 are required to promote differentiation of prechondrogenic mesenchymal cells to cartilage-producing chondrocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15781473" 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="#67" class="mim-tip-reference" title="Matsushita, T., Wilcox, W. R., Chan, Y. Y., Kawanami, A., Bukulmez, H., Balmes, G., Krejci, P., Mekikian, P. B., Otani, K., Yamaura, I., Warman, M. L., Givol, D., Murakami, S. <strong>FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway.</strong> Hum. Molec. Genet. 18: 227-240, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18923003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18923003</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18923003[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/ddn339" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18923003">Matsushita et al. (2009)</a> observed that chondrocyte-specific activation of Fgfr3 in mice induced premature synchondrosis closure and enhanced osteoblast differentiation around synchondroses. FGF signaling in chondrocytes increased bone morphogenetic protein ligand (e.g., BMP7, <a href="/entry/112267">112267</a>) mRNA expression and decreased Bmp antagonist (e.g., noggin, <a href="/entry/602991">602991</a>) mRNA expression in a MAPK-dependent manner, suggesting a role for Bmp signaling in the increased bone formation. The enhanced bone formation would accelerate the fusion of ossification centers and limit the endochondral bone growth. The authors proposed that spinal canal and foramen magnum stenosis in heterozygous achondroplasia patients may occur through premature synchondrosis closure. If this is the case, then any growth-promoting treatment for these complications of achondroplasia must precede the timing of the synchondrosis closure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18923003" 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>Ectopic activation of FGFR3 is associated with several cancers, including multiple myeloma (<a href="/entry/254500">254500</a>). <a href="#102" class="mim-tip-reference" title="Salazar, L., Kashiwada, T., Krejci, P., Muchowski, P., Donoghue, D., Wilcox, W. R., Thompson, L. M. <strong>A novel interaction between fibroblast growth factor receptor 3 and the p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation of ERK by p85 in multiple myeloma cells.</strong> Hum. Molec. Genet. 18: 1951-1961, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19286672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19286672</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19286672[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/ddp116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19286672">Salazar et al. (2009)</a> identified the PI3K regulatory subunit PIK3R1 (<a href="/entry/134934">134934</a>) as a novel interactor of FGFR3 by yeast 2-hybrid screen and confirmed an interaction between FGFR3 and PIK3R1 and PIK3R2 (<a href="/entry/603157">603157</a>) in mammalian cells. The interaction of FGFR3 with PIK3R1 was dependent upon receptor activation. In contrast to the Gab1 (<a href="/entry/604439">604439</a>)-mediated association of FGFRs with PIK3R1, the FGFR3-PIK3R1 interaction required FGFR3 tyr760, previously identified as a PLC-gamma (PLCG1; <a href="/entry/172420">172420</a>)-binding site. Interaction of PIK3R1 with FGFR3 did not require PLC-gamma, suggesting that PIK3R1 interaction was direct and independent of PLC-gamma binding. FGFR3 and PIK3R1/PIK3R2 proteins also interacted in multiple myeloma cell lines, which consistently express PIK3R1 p85 isoforms but not p50 or p55 isoforms, or PIK3R3 (<a href="/entry/606076">606076</a>). siRNA knockdown of PIK3R2 in multiple myeloma cells caused an increased ERK response to FGF2 stimulation. <a href="#102" class="mim-tip-reference" title="Salazar, L., Kashiwada, T., Krejci, P., Muchowski, P., Donoghue, D., Wilcox, W. R., Thompson, L. M. <strong>A novel interaction between fibroblast growth factor receptor 3 and the p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation of ERK by p85 in multiple myeloma cells.</strong> Hum. Molec. Genet. 18: 1951-1961, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19286672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19286672</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19286672[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/ddp116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19286672">Salazar et al. (2009)</a> suggested that an endogenous negative regulatory role for the PIK3R-FGFR3 interaction on the Ras/ERK/MAPK pathway may exist in response to FGFR3 activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19286672" 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>Botulinum neurotoxin A causes muscle paralysis by entering motor nerve terminals, where it cleaves SNAP25 (<a href="/entry/600322">600322</a>) and ultimately inhibits acetylcholine release. <a href="#49" class="mim-tip-reference" title="Jacky, B. P. S., Garay, P. E., Dupuy, J., Nelson, J. B., Cai, B., Molina, Y., Wang, J., Steward, L. E., Broide, R. S., Francis, J., Aoki, K. R., Stevens, R. C., Fernandez-Salas, E. <strong>Identification of fibroblast growth factor receptor 3 (FGFR3) as a protein receptor for botulinum neurotoxin serotype A (BoNT/A).</strong> PLoS Pathog. 9: e1003369, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23696738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23696738</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23696738[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/10.1371/journal.ppat.1003369" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23696738">Jacky et al. (2013)</a> noted that structural analysis of botulinum neurotoxin A had revealed that the heavy chain A domain (Hc/A) is a structural homolog of FGF2. Using pull-down analyses and other studies in mouse, rat, and human cells, <a href="#49" class="mim-tip-reference" title="Jacky, B. P. S., Garay, P. E., Dupuy, J., Nelson, J. B., Cai, B., Molina, Y., Wang, J., Steward, L. E., Broide, R. S., Francis, J., Aoki, K. R., Stevens, R. C., Fernandez-Salas, E. <strong>Identification of fibroblast growth factor receptor 3 (FGFR3) as a protein receptor for botulinum neurotoxin serotype A (BoNT/A).</strong> PLoS Pathog. 9: e1003369, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23696738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23696738</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23696738[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/10.1371/journal.ppat.1003369" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23696738">Jacky et al. (2013)</a> identified FGFR3 as a binding partner for botulinum neurotoxin A, with Hc/A of botulinum neurotoxin A specifically binding the second and third extracellular loops of FGFR3. Immunofluorescence microscopy demonstrated Fgfr3 expression at rat motor nerve terminals. <a href="#49" class="mim-tip-reference" title="Jacky, B. P. S., Garay, P. E., Dupuy, J., Nelson, J. B., Cai, B., Molina, Y., Wang, J., Steward, L. E., Broide, R. S., Francis, J., Aoki, K. R., Stevens, R. C., Fernandez-Salas, E. <strong>Identification of fibroblast growth factor receptor 3 (FGFR3) as a protein receptor for botulinum neurotoxin serotype A (BoNT/A).</strong> PLoS Pathog. 9: e1003369, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23696738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23696738</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23696738[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/10.1371/journal.ppat.1003369" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23696738">Jacky et al. (2013)</a> concluded that FGFR3 is a high-affinity receptor for botulinum neurotoxin A, which uses the same regions of FGFR3 as native ligands and induces FGFR3 phosphorylation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23696738" 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>Although there are significant exceptions to this generalization, dominant mutations in the FGFR3 gene affect predominantly bones that develop by endochondral ossification, whereas dominant mutations involving FGFR1 (<a href="/entry/136350">136350</a>) and FGFR2 (<a href="/entry/176943">176943</a>) principally cause syndromes that involve bones arising by membranous ossification, e.g., Pfeiffer syndrome (<a href="/entry/101600">101600</a>), Crouzon syndrome (<a href="/entry/123500">123500</a>), Apert syndrome (<a href="/entry/101200">101200</a>), Saethre-Chotzen syndrome (<a href="/entry/101400">101400</a>), Beare-Stevenson cutis gyrata (<a href="/entry/123790">123790</a>), and Jackson-Weiss syndrome (<a href="/entry/123150">123150</a>). The FGFR3 nucleotides mutated in most cases of achondroplasia (ACH; <a href="/entry/100800">100800</a>) and Muenke nonsyndromic craniosynostosis (<a href="/entry/602849">602849</a>) are among the most highly mutable nucleotides in the human genome.</p><p>The various seemingly diverse disorders due to mutations in the FGFR3 gene were recognized on phenotypic grounds by <a href="#111" class="mim-tip-reference" title="Spranger, J. <strong>Bone dysplasia 'families'.</strong> Path. Immunopath. Res. 7: 76-80, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3222210/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3222210</a>] [<a href="https://doi.org/10.1159/000157098" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3222210">Spranger (1988)</a> to represent a family of skeletal dysplasias. <a href="#111" class="mim-tip-reference" title="Spranger, J. <strong>Bone dysplasia 'families'.</strong> Path. Immunopath. Res. 7: 76-80, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3222210/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3222210</a>] [<a href="https://doi.org/10.1159/000157098" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3222210">Spranger (1988)</a> suggested that the achondroplasia family is characterized by a continuum of severity ranging from mild (hypochondroplasia, HCH; <a href="/entry/146000">146000</a>) and more severe forms (achondroplasia) to lethal neonatal dwarfism (thanatophoric dysplasia, TD; <a href="/entry/187600">187600</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3222210" 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="#82" class="mim-tip-reference" title="Passos-Bueno, M. R., Wilcox, W. R., Jabs, E. W., Sertie, A. L., Alonso, L. G., Kitoh, H. <strong>Clinical spectrum of fibroblast growth factor receptor mutations.</strong> Hum. Mutat. 14: 115-125, 1999. Note: Erratum: Hum. Mutat. 17: 431 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10425034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10425034</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)14:2<115::AID-HUMU3>3.0.CO;2-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10425034">Passos-Bueno et al. (1999)</a> provided an up-to-date listing of the mutations in FGFR1, FGFR2, and FGFR3 associated with distinct clinical entities, including achondroplasia; hypochondroplasia; (HCH; <a href="/entry/146000">146000</a>), platyspondylic lethal skeletal dysplasia (see <a href="/entry/151210">151210</a>), thanatophoric dysplasia (see <a href="/entry/187600">187600</a> and <a href="/entry/187601">187601</a>), Antley-Bixler syndrome (<a href="/entry/207410">207410</a>), Apert syndrome, Beare-Stevenson syndrome, Crouzon syndrome, Jackson-Weiss syndrome, Pfeiffer syndrome, and Saethre-Chotzen syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10425034" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study in Taiwan, <a href="#124" class="mim-tip-reference" title="Tsai, F.-J., Tsai, C.-H., Chang, J.-G., Wu, J.-Y. <strong>Mutations in the fibroblast growth factor receptor 3 (FGFR3) cause achondroplasia, hypochondroplasia, and thanatophoric dysplasia: Taiwanese data. (Letter)</strong> Am. J. Med. Genet. 86: 300-301, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10482885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10482885</a>]" pmid="10482885">Tsai et al. (1999)</a> found that all 28 cases of achondroplasia had the 1138G-A mutation (<a href="#0001">134934.0001</a>); 6 of 18 cases of hypochondroplasia had the 1620C-A mutation (<a href="#0010">134934.0010</a>); 4 of 18 had the 1620C-G mutation (<a href="#0012">134934.0012</a>), and 8 of the 18 had an undetermined mutation; and both of 2 cases of type I thanatophoric dysplasia had the 742C-T mutation (<a href="#0005">134934.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10482885" 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>Achondroplasia and Hypochondroplasia</em></strong></p><p>
|
|
<a href="#105" class="mim-tip-reference" title="Shiang, R., Thompson, L. M., Zhu, Y.-Z., Church, D. M., Fielder, T. J., Bocian, M., Winokur, S. T., Wasmuth, J. J. <strong>Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.</strong> Cell 78: 335-342, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7913883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7913883</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90302-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7913883">Shiang et al. (1994)</a> studied the FGFR3 gene as a candidate for the site of the mutation in achondroplasia (ACH; <a href="/entry/100800">100800</a>), which maps to the same region. DNA studies revealed point mutations in the FGFR3 gene in both ACH heterozygotes and homozygotes. The mutation on 15 of 16 ACH-affected chromosomes was the same: a G-to-A transition at nucleotide 1138 of the cDNA (<a href="#0001">134934.0001</a>). The mutation on the other ACH-affected chromosome 4 without the G-to-A transition at nucleotide 1138 had a G-to-C transversion at the same position. Both mutations resulted in the substitution of an arginine residue for a glycine at position 380 of the mature protein, which is in the transmembrane domain of FGFR3. <a href="#97" class="mim-tip-reference" title="Rousseau, F., Bonaventure, J., Legeai-Mallet, L., Pelet, A., Rozet, J.-M., Maroteaux, P., Le Merrer, M., Munnich, A. <strong>Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.</strong> Nature 371: 252-254, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8078586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8078586</a>] [<a href="https://doi.org/10.1038/371252a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8078586">Rousseau et al. (1994)</a> confirmed these mutations by DNA analysis of 17 sporadic cases and 6 unrelated familial forms of achondroplasia. In a review of data on unrelated achondroplasts from multiple laboratories, <a href="#7" class="mim-tip-reference" title="Bellus, G. A., Hefferon, T. W., Ortiz de Luna, R. I., Hecht, J. T., Horton, W. A., Machado, M., Kaitila, I., McIntosh, I., Francomano, C. A. <strong>Achondroplasia is defined by recurrent G380R mutations of FGFR3.</strong> Am. J. Hum. Genet. 56: 368-373, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7847369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7847369</a>]" pmid="7847369">Bellus et al. (1995)</a> found that 150 were heterozygous for the G-to-A transition at nucleotide 1138 leading to the G380R substitution; 3 were heterozygous for the G-to-C transversion at nucleotide 1138 leading to the same G380R substitution (<a href="#0002">134934.0002</a>). One achondroplasia patient reported by <a href="#115" class="mim-tip-reference" title="Superti-Furga, A., Eich, G., Bucher, H. U., Wisser, J., Giedion, A., Gitzelmann, R., Steinmann, B. <strong>A glycine 375-to-cysteine substitution in the transmembrane domain of the fibroblast growth factor receptor-3 in a newborn with achondroplasia.</strong> Europ. J. Pediat. 154: 215-219, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7758520/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7758520</a>] [<a href="https://doi.org/10.1007/BF01954274" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7758520">Superti-Furga et al. (1995)</a> had a G-to-T transversion leading to a G375C (<a href="#0003">134934.0003</a>) amino acid substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7758520+7913883+7847369+8078586" 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="#57" class="mim-tip-reference" title="Lanning, R. W., Brown, C. A. <strong>An improved methodology for the detection of the common mutation in the FGFR3 gene responsible for achondroplasia.</strong> Hum. Mutat. 10: 496-499, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9401015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9401015</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1997)10:6<496::AID-HUMU13>3.0.CO;2-V" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9401015">Lanning and Brown (1997)</a> described an improved method for detecting the common 1138G-A mutation (G380R; <a href="#0001">134934.0001</a>). The mutation had typically been detected by SfcI digestion of amplified genomic DNA. <a href="#57" class="mim-tip-reference" title="Lanning, R. W., Brown, C. A. <strong>An improved methodology for the detection of the common mutation in the FGFR3 gene responsible for achondroplasia.</strong> Hum. Mutat. 10: 496-499, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9401015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9401015</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1997)10:6<496::AID-HUMU13>3.0.CO;2-V" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9401015">Lanning and Brown (1997)</a> showed that the SfcI digestion protocol does not consistently distinguish between DNA samples heterozygous and homozygous for the G1138A substitution, and illustrated how the misdiagnosis of a homozygous affected fetus for one carrying only 1 copy of the mutation could occur. The simple nonradioactive technique that they described could reliably and consistently detect the presence of the G1138A mutation in both the heterozygous and the homozygous state. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9401015" 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="#72" class="mim-tip-reference" title="Monsonego-Ornan, E., Adar, R., Feferman, T., Segev, O., Yayon, A. <strong>The transmembrane mutation G380R in fibroblast growth factor receptor 3 uncouples ligand-mediated receptor activation from down-regulation.</strong> Molec. Cell. Biol. 20: 516-522, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10611230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10611230</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10611230[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.20.2.516-522.2000" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10611230">Monsonego-Ornan et al. (2000)</a> analyzed the biochemical consequences of the G380R point mutation that leads to achondroplasia. They found that dimerization and activation of the G380R mutant receptor was predominantly ligand dependent. However, they found a delay in the down-regulation of the mutant receptor, and it was resistant to ligand-mediated internalization. Transgenic mice expressing the human G380R mutant receptor demonstrated a markedly expanded area of FGFR3 immunoreactivity within their epiphyseal growth plates, which is compatible with an in vivo defect in receptor down-regulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10611230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The epiphyseal growth plates of individuals carrying the G380R substitution in the FGFR3 gene, the most common cause of achondroplasia, are disorganized and hypocellular and show aberrant chondrocyte maturation. To examine the molecular basis of these abnormalities, <a href="#38" class="mim-tip-reference" title="Henderson, J. E., Naski, M. C., Aarts, M. M., Wang, D., Cheng, L., Goltzman, D., Ornitz, D. M. <strong>Expression of FGFR3 with the G380R achondroplasia mutation inhibits proliferation and maturation of CFK2 chondrocytic cells.</strong> J. Bone Miner. Res. 15: 155-165, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10646125/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10646125</a>] [<a href="https://doi.org/10.1359/jbmr.2000.15.1.155" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10646125">Henderson et al. (2000)</a> used a chondrocyte cell line, CFK2, to study the effects of the constitutively active FGFR3 with the G380R substitution. Overexpression of FGFR3 had minimal effects on CFK2 proliferation and maturation compared with the severe growth retardation found in cells expressing the mutant form. Cells expressing the mutant receptor also showed an abnormal apoptotic response to serum deprivation and failed to undergo differentiation under appropriate culture conditions. These changes were associated with altered expression of integrin subunits, which effectively led to a switch in substrate preference of the immature cell from fibronectin to type II collagen. These observations supported those from in vivo studies indicating that FGFR3 mediates an inhibitory influence on chondrocyte proliferation. The authors suggested that the mechanism is related to altered integrin expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10646125" 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="#114" class="mim-tip-reference" title="Su, Y.-N., Lee, C.-N., Chien, S.-C., Hung, C.-C., Chien, Y.-H., Chen, C.-A. <strong>Rapid detection of FGFR3 gene mutation in achondroplasia by DHPLC system-coupling heteroduplex and fluorescence-enhanced primer-extension analysis.</strong> J. Hum. Genet. 49: 399-403, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15221641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15221641</a>] [<a href="https://doi.org/10.1007/s10038-004-0165-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15221641">Su et al. (2004)</a> introduced denaturing high-performance liquid chromatography (DHPLC) for detection of the 1138G-A mutation, the most common FGFR3 mutation causing achondroplasia. After coupling heteroduplex and fluorescence-enhanced primer-extension analysis, all affected patients with the 1138G-A mutation were successfully identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15221641" 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="Cho, J. Y., Guo, C., Torello, M., Lunstrum, G. P., Iwata, T., Deng, C., Horton, W. A. <strong>Defective lysosomal targeting of activated fibroblast growth factor receptor 3 in achondroplasia.</strong> Proc. Nat. Acad. Sci. 101: 609-614, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14699054/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14699054</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14699054[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.2237184100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14699054">Cho et al. (2004)</a> presented evidence indicating that activated FGFR3 is targeted for lysosomal degradation by c-Cbl-mediated ubiquitination, and that activating mutations found in patients with achondroplasia and related chondrodysplasias disturb this process, leading to recycling of activated receptors and amplification of FGFR3 signals. They suggested that this mechanism contributes to the molecular pathogenesis of achondroplasia and represents a potential target for therapeutic intervention. The lysosomal targeting defect is additive to other mechanisms proposed to explain the pathogenesis of achondroplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14699054" 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="#58" class="mim-tip-reference" title="Leroy, J. G., Nuytinck, L., Lambert, J., Naeyaert, J.-M., Mortier, G. R. <strong>Acanthosis nigricans in a child with mild osteochondrodysplasia and K650Q mutation in the FGFR3 gene.</strong> Am. J. Med. Genet. 143A: 3144-3149, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18000903/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18000903</a>] [<a href="https://doi.org/10.1002/ajmg.a.31966" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18000903">Leroy et al. (2007)</a> identified the lys650-to-asn mutation (<a href="#0022">134934.0022</a>) in an 8-year-old girl with mild hypochondroplasia and acanthosis nigricans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18000903" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#40" class="mim-tip-reference" title="Heuertz, S., Le Merrer, M., Zabel, B., Wright, M., Legeai-Mallet, L., Cormier-Daire, V., Gibbs, L., Bonaventure, J. <strong>Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.</strong> Europ. J. Hum. Genet. 14: 1240-1247, 2006. Note: Erratum: Europ. J. Hum. Genet. 14: 1321 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16912704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16912704</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201700" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16912704">Heuertz et al. (2006)</a> screened 18 exons of the FGFR3 gene in 25 patients with HCH and 1 with ACH in whom the common mutations G380R and N540K had been excluded. The authors identified 7 novel missense mutations, 1 in the patient with ACH (S279C; <a href="#0030">134934.0030</a>) and 6 in patients with HCH (see e.g., Y278C, <a href="#0031">134934.0031</a> and S84L, <a href="#0032">134934.0032</a>); no mutations were detected in the remaining 19 patients who were diagnosed clinically with HCH. <a href="#40" class="mim-tip-reference" title="Heuertz, S., Le Merrer, M., Zabel, B., Wright, M., Legeai-Mallet, L., Cormier-Daire, V., Gibbs, L., Bonaventure, J. <strong>Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.</strong> Europ. J. Hum. Genet. 14: 1240-1247, 2006. Note: Erratum: Europ. J. Hum. Genet. 14: 1321 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16912704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16912704</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201700" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16912704">Heuertz et al. (2006)</a> noted that 4 of the 6 extracellular mutations created additional cysteine residues and were associated with severe phenotypes. <a href="#28" class="mim-tip-reference" title="Friez, M. J., Wilson, J. A. P. <strong>Novel FGFR3 mutations in exon 7 and implications for expanded screening of achondroplasia and hypochondroplasia: a response to Heuertz et al. (Letter)</strong> Europ. J. Hum. Genet. 16: 277-278, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17895900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17895900</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201931" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17895900">Friez and Wilson (2008)</a> agreed with the recommendations of <a href="#40" class="mim-tip-reference" title="Heuertz, S., Le Merrer, M., Zabel, B., Wright, M., Legeai-Mallet, L., Cormier-Daire, V., Gibbs, L., Bonaventure, J. <strong>Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.</strong> Europ. J. Hum. Genet. 14: 1240-1247, 2006. Note: Erratum: Europ. J. Hum. Genet. 14: 1321 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16912704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16912704</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201700" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16912704">Heuertz et al. (2006)</a> to screen exon 7 of the FGFR3 gene in patients negative for more common variants. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17895900+16912704" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Almeida, M. R., Campos-Xavier, A. B., Medeira, A., Cordeiro, I., Sousa, A. B., Lima, M., Soares, G., Rocha, M., Saraiva, J., Ramos, L., Sousa, S., Marcelino, J. P., Correia, A., Santos, H. G. <strong>Clinical and molecular diagnosis of the skeletal dysplasias associated with mutations in the gene encoding fibroblast growth factor receptor 3 (FGFR3) in Portugal.</strong> Clin. Genet. 75: 150-156, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19215249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19215249</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2008.01123.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19215249">Almeida et al. (2009)</a> searched for mutations in the FGFR3 gene in 125 Portuguese patients with clinical and radiologic diagnoses of skeletal disorders, including achondroplasia (24), hypochondroplasia (46), Muenke craniosynostosis (52), thanatophoric dysplasia (2), and LADD syndrome (1). A P250R mutation (<a href="#0014">134934.0014</a>) was identified in 9 (17%) of 52 patients with Muenke craniosynostosis. FGFR3 mutations were found in both cases of thanatophoric dysplasia, and no mutations were identified in the patient with LADD syndrome. Five different mutations were identified in 36 (51%) of 70 patients with achondroplasia or hypochondroplasia; 10 of these diagnoses were reversed based on the molecular findings. The remaining 34 cases of achondroplasia/hypochondroplasia had no FGFR3 sequence changes. <a href="#1" class="mim-tip-reference" title="Almeida, M. R., Campos-Xavier, A. B., Medeira, A., Cordeiro, I., Sousa, A. B., Lima, M., Soares, G., Rocha, M., Saraiva, J., Ramos, L., Sousa, S., Marcelino, J. P., Correia, A., Santos, H. G. <strong>Clinical and molecular diagnosis of the skeletal dysplasias associated with mutations in the gene encoding fibroblast growth factor receptor 3 (FGFR3) in Portugal.</strong> Clin. Genet. 75: 150-156, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19215249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19215249</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2008.01123.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19215249">Almeida et al. (2009)</a> proposed a molecular strategy to test patients referred with a clinical diagnosis of achondroplasia or hypochondroplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19215249" 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 microarray-based next-generation sequencing, <a href="#129" class="mim-tip-reference" title="Wang, H., Sun, Y., Wu, W., Wei, X., Lan, Z., Xie, J. <strong>A novel missense mutation of FGFR3 in a Chinese female and her fetus with hypochondroplasia by next-generation sequencing.</strong> Clin. Chim. Acta 423: 62-65, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23726269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23726269</a>] [<a href="https://doi.org/10.1016/j.cca.2013.04.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23726269">Wang et al. (2013)</a> identified a G342C mutation (<a href="#0036">134934.0036</a>) in the extracellular IgIII loop of FGFR3 in a Chinese woman with hypochondroplasia. The mutation was also found in the woman's fetus when ultrasound scan detected an abnormally short femur at 28 weeks' gestation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23726269" 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>Thanatophoric Dysplasia</em></strong></p><p>
|
|
Thanatophoric dysplasia type I and type II (TD1, <a href="/entry/187600">187600</a>; TD2, <a href="/entry/187601">187601</a>) resembles homozygous achondroplasia in some respects. <a href="#120" class="mim-tip-reference" title="Tavormina, P. L., Shiang, R., Thompson, L. M., Zhu, Y.-Z., Wilkin, D. J., Lachman, R. S., Wilcox, W. R., Rimoin, D. L., Cohn, D. H., Wasmuth, J. J. <strong>Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3.</strong> Nature Genet. 9: 321-328, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7773297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7773297</a>] [<a href="https://doi.org/10.1038/ng0395-321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7773297">Tavormina et al. (1995)</a> found mutations in TD type I families that involved the substitution of a cysteine residue for the native amino acid (R248C, <a href="#0005">134934.0005</a>; S371C, <a href="#0006">134934.0006</a>). In all 16 individuals with type II thanatophoric dysplasia (TD2; <a href="/entry/187601">187601</a>), they found a sporadic heterozygous mutation causing a lys650-to-glu change in the FGFR3 tyrosine kinase domain (<a href="#0004">134934.0004</a>). <a href="#119" class="mim-tip-reference" title="Tavormina, P. L., Rimoin, D. L., Cohn, D. H., Zhu, Y.-Z., Shiang, R., Wasmuth, J. J. <strong>Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type I.</strong> Hum. Molec. Genet. 4: 2175-2177, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589699</a>] [<a href="https://doi.org/10.1093/hmg/4.11.2175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8589699">Tavormina et al. (1995)</a> described another TD1-associated cysteine-generating mutation in the extracellular domain of FGFR3 (S249C; <a href="#0013">134934.0013</a>). The authors speculated that the unpaired cysteine residue in this region of the protein might result in formation of intermolecular disulfide bonds between 2 mutant FGFR3 monomers and thereby constitutively activate the receptor complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7773297+8589699" 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="#98" class="mim-tip-reference" title="Rousseau, F., El Ghouzzi, V., Delezoide, A. L., Legeai-Mallet, L., Le Merrer, M., Munnich, A., Bonaventure, J. <strong>Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1).</strong> Hum. Molec. Genet. 5: 509-512, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845844</a>] [<a href="https://doi.org/10.1093/hmg/5.4.509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845844">Rousseau et al. (1996)</a> performed FGFR3 mutation analysis in 26 cases of TD1. Three missense mutations (Y373C, R248C, and S249C) accounted for 73% of the cases. Two stop codon mutations (X807R, <a href="#0008">134934.0008</a>; X807C, <a href="#0009">134934.0009</a>) and 1 rare G370C mutation (<a href="#0033">134934.0033</a>) were also found. <a href="#98" class="mim-tip-reference" title="Rousseau, F., El Ghouzzi, V., Delezoide, A. L., Legeai-Mallet, L., Le Merrer, M., Munnich, A., Bonaventure, J. <strong>Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1).</strong> Hum. Molec. Genet. 5: 509-512, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845844</a>] [<a href="https://doi.org/10.1093/hmg/5.4.509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845844">Rousseau et al. (1996)</a> noted that all reported missense mutations created cysteine residues and were located in the extracellular domain of the receptor. The findings provided support for the hypothesis that the newly created cysteine residues may allow disulfide bonds to form between the extracellular domains of mutant monomers, thus inducing constitutive activation of the homodimer receptor complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845844" 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="#76" class="mim-tip-reference" title="Naski, M. C., Wang, Q., Xu, J., Ornitz, D. M. <strong>Graded activation of fibroblast growth factor receptor 3 by mutations causing achondroplasia and thanatophoric dysplasia.</strong> Nature Genet. 13: 233-237, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8640234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8640234</a>] [<a href="https://doi.org/10.1038/ng0696-233" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8640234">Naski et al. (1996)</a> studied the effect of the achondroplasia and thanatophoric dysplasia mutations on the activity and regulation of FGFR3 by transient transfection of NIH3T3 and BaF3 pro-B cells with mutant FGFR3 cDNAs. They showed that each of the mutations studied (R248C, K650E, and G380R) constitutively activates the receptor, as evidenced by ligand-independent receptor tyrosine phosphorylation and cell proliferation. Moreover, the mutations responsible for TD (R248C and K650E) were more strongly activating than the mutation causing ACH (G380R), providing to <a href="#76" class="mim-tip-reference" title="Naski, M. C., Wang, Q., Xu, J., Ornitz, D. M. <strong>Graded activation of fibroblast growth factor receptor 3 by mutations causing achondroplasia and thanatophoric dysplasia.</strong> Nature Genet. 13: 233-237, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8640234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8640234</a>] [<a href="https://doi.org/10.1038/ng0696-233" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8640234">Naski et al. (1996)</a> a biochemical explanation for the observation that the phenotype of TD is more severe than that of ACH. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8640234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The San Diego form of skeletal dysplasia (<a href="/entry/187600">187600</a>) has features similar to those of thanatophoric dysplasia but was thought to be distinguished by the presence of large inclusion bodies in the rough endoplasmic reticulum (rER) within chondrocytes. <a href="#11" class="mim-tip-reference" title="Brodie, S. G., Kitoh, H., Lachman, R. S., Nolasco, L. M., Mekikian, P. B., Wilcox, W. R. <strong>Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by FGFR3 mutations.</strong> Am. J. Med. Genet. 84: 476-480, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10360402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10360402</a>]" pmid="10360402">Brodie et al. (1999)</a> found that all 17 cases of the San Diego type of skeletal dysplasia were heterozygous for the same FGFR3 mutations found in TD1, e.g., R248C (<a href="#0005">134934.0005</a>) present in 7 of 17 cases, S249C (<a href="#0013">134934.0013</a>) present in 2 of 17 cases, and Y373C (<a href="#0016">134934.0016</a>) present in 6 of 17 cases. No mutations were identified in cases of the so-called Torrance or Luton types of skeletal dysplasia (<a href="/entry/151210">151210</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10360402" 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>Observations in thanatophoric dysplasia type II and in mice with homozygous disruption of FGFR3 (<a href="#21" class="mim-tip-reference" title="Deng, C., Wynshaw-Boris, A., Zhou, F., Kuo, A., Leder, P. <strong>Fibroblast growth factor receptor 3 is a negative regulator of bone growth.</strong> Cell 84: 911-921, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8601314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8601314</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81069-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8601314">Deng et al., 1996</a>; <a href="#19" class="mim-tip-reference" title="Colvin, J. S., Bohne, B. A., Harding, G. W., McEwen, D. G., Ornitz, D. M. <strong>Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3.</strong> Nature Genet. 12: 390-397, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8630492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8630492</a>] [<a href="https://doi.org/10.1038/ng0496-390" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8630492">Colvin et al., 1996</a>) indicate that FGFR3 may inhibit cell growth in cartilaginous growth plates, and that the disease-associated mutants have a gain-of-function nature. <a href="#113" class="mim-tip-reference" title="Su, W.-C. S., Kitagawa, M., Xue, N., Xie, B., Garofalo, S., Cho, J., Deng, C., Horton, W. A., Fu, X.-Y. <strong>Activation of Stat1 by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism.</strong> Nature 386: 288-292, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9069288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9069288</a>] [<a href="https://doi.org/10.1038/386288a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9069288">Su et al. (1997)</a> showed that mutant TD2 FGFR3 has a constitutive tyrosine kinase activity that can specifically activate transcription factor STAT1 (<a href="/entry/600555">600555</a>). Furthermore, expression of TD2 FGFR3 with the lys650-to-glu mutation (<a href="#0004">134934.0004</a>) induced nuclear translocation of STAT1, expression of the cell cycle inhibitor p21(WAF1/CIP1) (CDKNA1; <a href="/entry/116899">116899</a>), and growth arrest of the cell. Thus, TD2 FGFR3 may use STAT1 as a mediator of growth retardation in bone development. Consistent with this, STAT1 activation and increased p21(WAF1/CIP1) expression was found in the cartilage cells from a TD2 fetus, but not in those from a normal fetus. Thus, abnormal STAT activation and p21(WAF1/CIP1) expression by the TD2 mutant receptor may be responsible for this particular form of FGFR3-related bone disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8601314+8630492+9069288" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The lys650 codon of FGFR3 is located within a critical region of the tyrosine kinase domain activation loop. Two missense mutations in this codon result in strong constitutive activation of the FGFR3 tyrosine kinase and cause 3 different skeletal dysplasia syndromes: thanatophoric dysplasia type II caused by lys650 to glu (<a href="#0004">134934.0004</a>) and SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans; <a href="/entry/616482">616482</a>) and thanatophoric dysplasia type I, both due to lys650 to met (<a href="#0015">134934.0015</a>). Other mutations within the FGFR3 tyrosine kinase domain, e.g., 1620C-A or 1620C-G (both resulting in asn540 to lys (<a href="#0010">134934.0010</a> and <a href="#0012">134934.0012</a>)) cause hypochondroplasia, a relatively common but milder skeletal dysplasia. In 90 individuals with suspected clinical diagnoses of hypochondroplasia who did not have the asn540-to-lys mutations, <a href="#9" class="mim-tip-reference" title="Bellus, G. A., Spector, E. B., Speiser, P. W., Weaver, C. A., Garber, A. T., Bryke, C. R., Israel, J., Rosengren, S. S., Webster, M. K., Donoghue, D. J., Francomano, C. A. <strong>Distinct missense mutations of the FGFR3 lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype.</strong> Am. J. Hum. Genet. 67: 1411-1421, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11055896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11055896</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11055896[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/316892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11055896">Bellus et al. (2000)</a> screened for mutations, in FGFR3 exon 15, that would disrupt a unique BbsI restriction site that includes the lys650 codon. They discovered 3 novel mutations involving codon lys650: 1950G-T and 1950G-C (both resulting in lys650 to asn; <a href="#0020">134934.0020</a> and <a href="#0021">134934.0021</a>) and 1948A-C (resulting in lys650 to gln; <a href="#0022">134934.0022</a>), occurring in 6 individuals from 5 families. The lys650-to-asn and lys650-to-gln mutations resulted in constitutive activation of the FGFR3 tyrosine kinase but to a lesser degree than that observed with the lys650-to-glu and lys650-to-met mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11055896" 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>Crouzon Craniosynostosis with Acanthosis Nigricans</em></strong></p><p>
|
|
<a href="#69" class="mim-tip-reference" title="Meyers, G. A., Orlow, S. J., Munro, I. R., Przylepa, K. A., Jabs, E. W. <strong>Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans.</strong> Nature Genet. 11: 462-464, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7493034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7493034</a>] [<a href="https://doi.org/10.1038/ng1295-462" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7493034">Meyers et al. (1995)</a> identified an ala391-to-glu mutation (A391E; <a href="#0011">134934.0011</a>) in the FGFR3 gene in affected members of 3 unrelated families with a syndrome of Crouzon craniosynostosis with acanthosis nigricans (<a href="/entry/612247">612247</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7493034" 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>Muenke Coronal Craniosynostosis</em></strong></p><p>
|
|
<a href="#6" class="mim-tip-reference" title="Bellus, G. A., Gaudenz, K., Zackai, E. H., Clarke, L. A., Szabo, J., Francomano, C. A., Muenke, M. <strong>Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes.</strong> Nature Genet. 14: 174-176, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8841188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8841188</a>] [<a href="https://doi.org/10.1038/ng1096-174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8841188">Bellus et al. (1996)</a> described a pro250-to-arg mutation (P250R; <a href="#0014">134934.0014</a>) in FGFR3. On the basis of 61 individuals from 20 unrelated families where coronal synostosis (<a href="/entry/602849">602849</a>) was due to the P250R mutation in the FGFR3 gene, <a href="#74" class="mim-tip-reference" title="Muenke, M., Gripp, K. W., McDonald-McGinn, D. M., Gaudenz, K., Whitaker, L. A., Bartlett, S. P., Markowitz, R. I., Robin, N. H., Nwokoro, N., Mulvihill, J. J., Losken, W., Mulliken, J. B., Guttmacher, A. E., Wilroy, R. S., Clarke, L. A., Hollway, G., Ades, L. C., Haan, E. A., Mulley, J. C., Cohen, M. M., Jr., Bellus, G. A., Francomano, C. A., Moloney, D. M., Wall, S. A., Wilkie, A. O. M., Zackai, E. H. <strong>A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome.</strong> Am. J. Hum. Genet. 60: 555-564, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042914</a>]" pmid="9042914">Muenke et al. (1997)</a> defined a new clinical syndrome distinct from previously defined craniosynostosis syndromes, including the Pfeiffer (<a href="/entry/101600">101600</a>), Crouzon, Jackson-Weiss (<a href="/entry/123150">123150</a>), and Apert (<a href="/entry/101200">101200</a>) syndromes. In addition to the skull findings, some patients had abnormalities on radiographs of hands and feet, including thimble-like middle phalanges, coned epiphyses, and carpal and tarsal fusions. Brachydactyly was seen in some cases; none had clinically significant syndactyly or deviation of the great toe to suggest Apert syndrome or Pfeiffer syndrome, respectively. Sensorineural hearing loss was present in some and developmental delay was seen in a minority. While the radiologic findings of hands and feet can be helpful in the recognition of this syndrome, it was not in all cases clearly distinguishable on a clinical basis from other craniosynostosis syndromes. Therefore, <a href="#74" class="mim-tip-reference" title="Muenke, M., Gripp, K. W., McDonald-McGinn, D. M., Gaudenz, K., Whitaker, L. A., Bartlett, S. P., Markowitz, R. I., Robin, N. H., Nwokoro, N., Mulvihill, J. J., Losken, W., Mulliken, J. B., Guttmacher, A. E., Wilroy, R. S., Clarke, L. A., Hollway, G., Ades, L. C., Haan, E. A., Mulley, J. C., Cohen, M. M., Jr., Bellus, G. A., Francomano, C. A., Moloney, D. M., Wall, S. A., Wilkie, A. O. M., Zackai, E. H. <strong>A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome.</strong> Am. J. Hum. Genet. 60: 555-564, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042914</a>]" pmid="9042914">Muenke et al. (1997)</a> suggested that all patients with coronal synostosis should be tested for this mutation. We have designated this syndrome caused by the P250R mutation as Muenke syndrome (<a href="/entry/602849">602849</a>), or Muenke nonsyndromic coronal craniosynostosis. This is in parallel with the usage for Apert syndrome, Pfeiffer syndrome, Crouzon syndrome, Saethre-Chotzen syndrome, etc. The very tight relationship between genotype and phenotype is shared also by achondroplasia, Apert syndrome, and type IIB multiple endocrine neoplasia (MEN2B; <a href="/entry/164761#0013">164761.0013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9042914+8841188" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a cohort of 182 Spanish probands with craniosynostosis, <a href="#83" class="mim-tip-reference" title="Paumard-Hernandez, B., Berges-Soria, J., Barroso, E., Rivera-Pedroza, C. I., Perez-Carrizosa, V., Benito-Sanz, S., Lopez-Messa, E., Santos, F., Garcia-Recuero, I. I., Romance, A., Ballesta-Martinez, M. J., Lopez-Gonzalez, V., Campos-Barros, A., Cruz, J., Guillen-Navarro, E., Sanchez del Pozo, J., Lapunzina, P., Garcia-Minaur, S., Heath, K. E. <strong>Expanding the mutation spectrum in 182 Spanish probands with craniosynostosis: identification and characterization of novel TCF12 variants.</strong> Europ. J. Hum. Genet. 23: 907-914, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25271085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25271085</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25271085[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2014.205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25271085">Paumard-Hernandez et al. (2015)</a> screened 5 craniosynostosis-associated genes, including FGFR1, FGFR2, FGFR3, TWIST1 (<a href="/entry/601622">601622</a>), and EFNB1 (<a href="/entry/300035">300035</a>). The most frequent mutation was the characteristic Muenke syndrome mutation, P250R in FGFR3, which was detected in 24 patients (13.2% of the cohort). The authors noted that this was somewhat lower than the 24% detected in a UK study of craniosynostosis patients by <a href="#132" class="mim-tip-reference" title="Wilkie, A. O. M., Byren, J. C., Hurst, J. A., Jayamohan, J., Johnson, D., Knight, S. J. L., Lester, T., Richards, P. G., Twigg, S. R. F., Wall, S. A. <strong>Prevalence and complications of single-gene and chromosomal disorders in craniosynostosis.</strong> Pediatrics 126: e391-e400, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20643727/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20643727</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20643727[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/10.1542/peds.2009-3491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20643727">Wilkie et al. (2010)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20643727+25271085" 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>Lacrimoauriculodentodigital (LADD) Syndrome 2</em></strong></p><p>
|
|
Lacrimoauriculodentodigital (LADD) syndrome-2 (LADD2; <a href="/entry/620192">620192</a>) is a multiple congenital anomaly mainly affecting lacrimal glands and ducts, salivary glands and ducts, ears, teeth, and distal limb segments. Using a positional cloning approach, <a href="#95" class="mim-tip-reference" title="Rohmann, E., Brunner, H. G., Kayserili, H., Uyguner, O., Nurnberg, G., Lew, E. D., Dobbie, A., Eswarakumar, V. P., Uzumcu, A., Ulubil-Emeroglu, M., Leroy, J. G., Li, Y., and 9 others. <strong>Mutations in different components of FGF signaling in LADD syndrome.</strong> Nature Genet. 38: 414-417, 2006. Note: Erratum: Nature Genet. 38: 495 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16501574/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16501574</a>] [<a href="https://doi.org/10.1038/ng1757" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16501574">Rohmann et al. (2006)</a> identified a heterozygous missense mutation in the FGFR3 gene in a father and his 2 children with LADD syndrome (D513N; <a href="#0028">134934.0028</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16501574" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 23-year-old proband and his affected mother in a consanguineous Iranian family with LADD syndrome, <a href="#117" class="mim-tip-reference" title="Talebi, F., Ghanbari Mardasi, F., Mohammadi Asl, J., Bavarsad, A. H., Tizno, S. <strong>Identification of a novel missence (sic) mutation in FGFR3 gene in an Iranian family with LADD syndrome by next-generation sequencing.</strong> Int. J. Pediat. Otorhinolaryng. 97: 192-196, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28483234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28483234</a>] [<a href="https://doi.org/10.1016/j.ijporl.2017.04.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28483234">Talebi et al. (2017)</a> identified heterozygosity for a missense mutation (D628N; <a href="#0038">134934.0038</a>) in the FGFR3 gene. The mutation was not identified in the unaffected father or in 400 control chromosomes. By family history, the proband's maternal uncle was also affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28483234" 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>Camptodactyly, Tall Stature, Scoliosis, and Hearing Loss Syndrome</em></strong></p><p>
|
|
The camptodactyly, tall stature, scoliosis, and hearing loss syndrome (CATSHL syndrome; <a href="/entry/610474">610474</a>) maps to chromosome 4p and recapitulates the phenotype of the Fgfr3 knockout mouse (<a href="#123" class="mim-tip-reference" title="Toydemir, R. M., Brassington, A. E., Bayrak-Toydemir, P., Krakowiak, P. A., Jorde, L. B., Whitby, F. G., Longo, N., Viskochil, D. H., Carey, J. C., Bamshad, M. J. <strong>A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome.</strong> Am. J. Hum. Genet. 79: 935-941, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033969</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033969[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508433" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033969">Toydemir et al., 2006</a>). In affected members of a large family with CATSHL syndrome, <a href="#123" class="mim-tip-reference" title="Toydemir, R. M., Brassington, A. E., Bayrak-Toydemir, P., Krakowiak, P. A., Jorde, L. B., Whitby, F. G., Longo, N., Viskochil, D. H., Carey, J. C., Bamshad, M. J. <strong>A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome.</strong> Am. J. Hum. Genet. 79: 935-941, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033969</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033969[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508433" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033969">Toydemir et al. (2006)</a> identified a heterozygous missense mutation in the FGFR3 gene (R621H; <a href="#0029">134934.0029</a>) predicted to cause partial loss of protein function. These findings indicated that abnormal FGFR3 signaling can cause human anomalies by promoting as well as inhibiting endochondral bone growth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17033969" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 brothers, born of consanguineous Egyptian parents, with autosomal recessive inheritance of camptodactyly, tall stature, and hearing loss, <a href="#65" class="mim-tip-reference" title="Makrythanasis, P., Temtamy, S., Aglan, M., Otaify, G. A., Hamamy, H., Antonarakis, S. E. <strong>A novel homozygous mutation in FGFR3 causes tall stature, severe lateral tibial deviation, scoliosis, hearing impairment, camptodactyly, and arachnodactyly.</strong> Hum. Mutat. 35: 959-963, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24864036/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24864036</a>] [<a href="https://doi.org/10.1002/humu.22597" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24864036">Makrythanasis et al. (2014)</a> identified a homozygous missense mutation in the FGFR3 gene (T546K; <a href="#0037">134934.0037</a>). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant were not performed, but <a href="#65" class="mim-tip-reference" title="Makrythanasis, P., Temtamy, S., Aglan, M., Otaify, G. A., Hamamy, H., Antonarakis, S. E. <strong>A novel homozygous mutation in FGFR3 causes tall stature, severe lateral tibial deviation, scoliosis, hearing impairment, camptodactyly, and arachnodactyly.</strong> Hum. Mutat. 35: 959-963, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24864036/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24864036</a>] [<a href="https://doi.org/10.1002/humu.22597" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24864036">Makrythanasis et al. (2014)</a> postulated a loss-of-function effect. The unaffected parents and an unaffected sister were heterozygous for the mutation, suggesting a differential functional effect of the mutation compared to that of the heterozygous mutation reported by <a href="#123" class="mim-tip-reference" title="Toydemir, R. M., Brassington, A. E., Bayrak-Toydemir, P., Krakowiak, P. A., Jorde, L. B., Whitby, F. G., Longo, N., Viskochil, D. H., Carey, J. C., Bamshad, M. J. <strong>A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome.</strong> Am. J. Hum. Genet. 79: 935-941, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033969</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033969[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508433" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033969">Toydemir et al. (2006)</a> in their family with CATSHL syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17033969+24864036" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Somatic Mutations in the FGFR3 Gene</em></strong></p><p>
|
|
Among 62 human cases of seborrheic keratosis (<a href="/entry/182000">182000</a>), <a href="#63" class="mim-tip-reference" title="Logie, A., Dunois-Larde, C., Rosty, C., Levrel, O., Blanche, M., Ribeiro, A., Gasc, J.-M., Jorcano, J., Werner, S., Sastre-Garau, X., Thiery, J. P., Radvanyi, F. <strong>Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans.</strong> Hum. Molec. Genet. 14: 1153-1160, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15772091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15772091</a>] [<a href="https://doi.org/10.1093/hmg/ddi127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15772091">Logie et al. (2005)</a> found that 39% of samples harbored somatic activating FGFR3 mutations, identical to those associated with skeletal dysplasia syndromes and bladder and cervical neoplasms (see, e.g., <a href="#0005">134934.0005</a> and <a href="#0013">134934.0013</a>). <a href="#63" class="mim-tip-reference" title="Logie, A., Dunois-Larde, C., Rosty, C., Levrel, O., Blanche, M., Ribeiro, A., Gasc, J.-M., Jorcano, J., Werner, S., Sastre-Garau, X., Thiery, J. P., Radvanyi, F. <strong>Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans.</strong> Hum. Molec. Genet. 14: 1153-1160, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15772091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15772091</a>] [<a href="https://doi.org/10.1093/hmg/ddi127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15772091">Logie et al. (2005)</a> implicated FGFR3 activation as a major cause of benign epidermal tumors in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15772091" 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="#35" class="mim-tip-reference" title="Hafner, C., van Oers, J. M. M., Vogt, T., Landthaler, M., Stoehr, R., Blaszyk, H., Hofstaedter, F., Zwarthoff, E. C., Hartmann, A. <strong>Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi.</strong> J. Clin. Invest. 116: 2201-2207, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16841094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16841094</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16841094[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/10.1172/JCI28163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16841094">Hafner et al. (2006)</a> analyzed 39 common epidermal nevi (<a href="/entry/162900">162900</a>) from 33 patients using a multiplex PCR assay covering 11 FGFR3 point mutations and by direct sequencing of exon 19 of the FGFR3 gene. Somatic mutations were identified in 11 patients, 10 of whom had the R248C mutation, and 1 had a double mutation in exon 10 of the FGFR3 gene (<a href="#0001">134934.0001</a> and <a href="#0033">134934.0033</a>). In 4 patients tested, FGFR3 mutations were not found in adjacent, histologically normal skin. <a href="#35" class="mim-tip-reference" title="Hafner, C., van Oers, J. M. M., Vogt, T., Landthaler, M., Stoehr, R., Blaszyk, H., Hofstaedter, F., Zwarthoff, E. C., Hartmann, A. <strong>Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi.</strong> J. Clin. Invest. 116: 2201-2207, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16841094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16841094</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16841094[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/10.1172/JCI28163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16841094">Hafner et al. (2006)</a> concluded that a large proportion of epidermal nevi are caused by mosaicism of activating FGFR3 mutations in the human epidermis secondary to a postzygotic mutation in early embryonic development, and that the R248C mutation appears to be a hotspot for FGFR3 mutations in epidermal nevi. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16841094" 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>Other Disease Associations</em></strong></p><p>
|
|
<a href="#93" class="mim-tip-reference" title="Riley, B. M., Mansilla, M. A., Ma, J., Daack-Hirsch, S., Maher, B. S., Raffensperger, L. M., Russo, E. T., Vieira, A. R., Dode, C., Mohammadi, M., Marazita, M. L., Murray, J. C. <strong>Impaired FGF signaling contributes to cleft lip and palate.</strong> Proc. Nat. Acad. Sci. 104: 4512-4517, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360555</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360555[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0607956104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17360555">Riley et al. (2007)</a> analyzed 12 genes involved in the fibroblast growth factor signaling pathway in nonsyndromic cleft lip or palate families and identified 7 likely disease-causing mutations in which structural analysis predicted functional impairment in the FGFR1, FGFR2, FGFR3, and FGF8 (<a href="/entry/600483">600483</a>) genes. <a href="#93" class="mim-tip-reference" title="Riley, B. M., Mansilla, M. A., Ma, J., Daack-Hirsch, S., Maher, B. S., Raffensperger, L. M., Russo, E. T., Vieira, A. R., Dode, C., Mohammadi, M., Marazita, M. L., Murray, J. C. <strong>Impaired FGF signaling contributes to cleft lip and palate.</strong> Proc. Nat. Acad. Sci. 104: 4512-4517, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360555</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360555[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0607956104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17360555">Riley et al. (2007)</a> suggested that the FGF signaling pathway may contribute to as much as 3 to 5% of nonsyndromic cleft lip or palate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17360555" 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>Role in Cancer</em></strong></p><p>
|
|
Dysregulation of oncogenes by translocation to the immunoglobulin heavy chain (IgH) locus (<a href="/entry/147100">147100</a>) on 14q32 is a seminal event in the pathogenesis of B-cell tumors. In multiple myeloma (<a href="/entry/254500">254500</a>), translocations to the IgH locus occur in 20 to 60% of cases. For most translocations, the partner chromosome is unknown; for the others, a diverse array of chromosomal partners have been identified, with 11q13 (see cyclin D1; <a href="/entry/168461">168461</a>) the only chromosome that is frequently involved. <a href="#10" class="mim-tip-reference" title="Bergsagel, P. L., Chesi, M., Nardini, E., Brents, L. A., Kirby, S. L., Kuehl, W. M. <strong>Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma.</strong> Proc. Nat. Acad. Sci. 93: 13931-13936, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8943038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8943038</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=8943038[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.93.24.13931" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8943038">Bergsagel et al. (1996)</a> developed a comprehensive Southern blot assay to identify and distinguish different kinds of IgH switch recombination events. Illegitimate switch recombination fragments (defined as containing sequences from only 1 switch region) are potential markers of translocation events into IgH switch regions and were identified in 15 of 21 myeloma cell lines, including 7 of 8 karyotyped lines that had no detectable 14q32 translocation. These translocation breakpoints involved 6 chromosomal loci: 4p16.3; 6; 8q24.13; 11q13.3; 16q23.1; and 21q22.1. <a href="#16" class="mim-tip-reference" title="Chesi, M., Nardini, E., Brents, L. A., Schrock, E., Ried, T., Kuehl, W. M., Bergsagel, P. L. <strong>Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3.</strong> Nature Genet. 16: 260-264, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9207791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9207791</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9207791[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng0797-260" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9207791">Chesi et al. (1997)</a> found the novel, karyotypically silent translocation t(4;14)(p16.3;q32.3) in 5 myeloma cells lines and in at least 3 of 10 primary tumors. The chromosome-4 breakpoints were clustered in a 70-kb region centromeric to FGFR3, which was thought to be the dysregulated oncogene. Two lines and 1 primary tumor with this translocation selectively expressed an FGFR3 allele containing activating mutations identified previously in thanatophoric dwarfism: tyr373 to cys (<a href="#0016">134934.0016</a>), lys650 to glu (<a href="#0004">134934.0004</a>), and lys650 to met (<a href="#0015">134934.0015</a>). For K650E, the constitutive activation of FGFR3 in the absence of ligand had been proved by transfection experiments. <a href="#16" class="mim-tip-reference" title="Chesi, M., Nardini, E., Brents, L. A., Schrock, E., Ried, T., Kuehl, W. M., Bergsagel, P. L. <strong>Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3.</strong> Nature Genet. 16: 260-264, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9207791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9207791</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9207791[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng0797-260" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9207791">Chesi et al. (1997)</a> proposed that after the t(4;14) translocation, somatic mutation during tumor progression frequently generates an FGFR3 protein that is active in the absence of ligand. Although they could not exclude the possibility that other genes are dysregulated by the translocation t(4;14), several findings pointed to FGFR3. FGFR3 is located no more than 100 kb from the most centromeric breakpoint at 4p16.3, and is on the derivative(14) chromosome that contains the 3-prime IgH enhancer. This is similar to the situation for cyclin D1, which is located 100 to 400 kb from the breakpoint in the translocation t(11;14) that occurs in mantle-cell lymphoma and multiple myeloma tumors. FGFR3 is another example of a gene that can function both as an oncogene and a 'teratogene.' <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8943038+9207791" 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="#91" class="mim-tip-reference" title="Rasmussen, T., Hudlebusch, H. R., Knudsen, L. M., Johnsen, H. E. <strong>FGFR3 dysregulation in multiple myeloma: frequency and prognostic relevance.</strong> Brit. J. Haemat. 117: 626-628, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12028033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12028033</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2002.03429.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12028033">Rasmussen et al. (2002)</a> cited a frequency of 3 to 24% for the t(4;14) translocation in multiple myeloma. The translocation was observed at a significantly lower frequency in patients with monoclonal gammopathy of undetermined significance (MGUS), suggesting a role in the transition from MGUS to multiple myeloma. The t(4;14) translocation affects 2 potential oncogenes: FGFR3 and MMSET (<a href="/entry/602952">602952</a>). <a href="#91" class="mim-tip-reference" title="Rasmussen, T., Hudlebusch, H. R., Knudsen, L. M., Johnsen, H. E. <strong>FGFR3 dysregulation in multiple myeloma: frequency and prognostic relevance.</strong> Brit. J. Haemat. 117: 626-628, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12028033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12028033</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2002.03429.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12028033">Rasmussen et al. (2002)</a> investigated the frequency of FGFR3 dysregulation and its prognostic value in multiple myeloma. In 16 of 110 (14.5%) multiple myeloma bone marrow samples, they found dysregulated FGFR3 expression. Follow-up of 76 multiple myeloma patients showed no significant difference between FGFR3 dysfunction and survival, and no correlation with prognostic factors. Further, no linear relation was observed between FGFR3 and MMSET levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12028033" 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="Cappellen, D., De Oliveira, C., Ricol, D., Gil Diez de Medina, S., Bourdin, J., Sastre-Garau, X., Chopin, D., Thiery, J. P., Radvanyi, F. <strong>Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. (Letter)</strong> Nature Genet. 23: 18-20, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10471491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10471491</a>] [<a href="https://doi.org/10.1038/12615" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10471491">Cappellen et al. (1999)</a> presented evidence indicating an oncogenic role for FGFR3 in carcinomas. They found expression of a constitutively activated FGFR3 in a large proportion of 2 common epithelial cancers, bladder (<a href="/entry/109800">109800</a>) and cervix (<a href="/entry/603956">603956</a>). FGFR3 appeared to be the most frequently mutated oncogene in bladder cancer, being mutated in more than 30% of cases. FGFR3 seems to mediate opposite signals, acting as a negative regulator of growth in bone and as an oncogene in several tumor types. All FGFR3 missense somatic mutations identified in these cancers were identical to the germinal activating mutations that cause thanatophoric dysplasia (the authors noted that in 2 mutations, this equivalency occurred because the FGFR3b isoform expressed in epithelial cells contains 2 more amino acids than the FGFR3c isoform expressed in bone). Of the FGFR3 alterations in epithelial tumors, the S249C mutation was the most common, affecting 5 of 9 bladder cancers and 3 of 3 cervical cancers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10471491" 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>Bladder cancer is the fourth most common cancer in males in the U.S. and the U.K. (<a href="#108" class="mim-tip-reference" title="Sibley, K., Cuthbert-Heavens, D., Knowles, M. A. <strong>Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell carcinoma.</strong> Oncogene 20: 686-691, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11314002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11314002</a>] [<a href="https://doi.org/10.1038/sj.onc.1204110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11314002">Sibley et al., 2001</a>). A region of nonrandom LOH in transitional cell carcinoma of the bladder, 4p16.3, suggests the presence of a tumor suppressor gene. <a href="#108" class="mim-tip-reference" title="Sibley, K., Cuthbert-Heavens, D., Knowles, M. A. <strong>Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell carcinoma.</strong> Oncogene 20: 686-691, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11314002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11314002</a>] [<a href="https://doi.org/10.1038/sj.onc.1204110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11314002">Sibley et al. (2001)</a> investigated the frequency and nature of FGFR3 mutations in a panel of transitional cell carcinomas and cell lines and studied the possible link between mutation and loss of heterozygosity in 4p16.3. Of 63 tumors studied, 31 had previously been assessed to have LOH at 4p16.3. Twenty-six of the 63 tumors (41%) and 4 of the 18 cell lines (22%) had missense mutations in FGFR3. All mutations detected in the panel were found in the germline, and all but one caused lethal conditions. One tumor contained K650Q (<a href="#0022">134934.0022</a>), which had been identified in less severe cases of skeletal dysplasia. Tumors with and without LOH at 4p16.3 had mutations in FGFR3, suggesting that these 2 events are not causally linked. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11314002" 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 SSCP and sequencing, <a href="#52" class="mim-tip-reference" title="Karoui, M., Hofmann-Radvanyi, H., Zimmermann, U., Couvelard, A., Degott, C., Faridoni-Laurens, L., Ahomadegbe, J.-C., Gazzeri, S., Brambilla, E., Clerici, T., Charbonnier, P., Tresallet, C., and 8 others. <strong>No evidence of somatic FGFR3 mutation in various types of carcinoma.</strong> Oncogene 20: 5059-5061, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11526491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11526491</a>] [<a href="https://doi.org/10.1038/sj.onc.1204651" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11526491">Karoui et al. (2001)</a> analyzed the prevalence of FGFR3 mutations in 116 primary tumors of various types (upper aerodigestive tract, esophagus, stomach, lung, and skin). The regions analyzed encompassed all FGFR3 point mutations previously described in severe skeletal dysplasia and cancers. No mutations were detected in the tumor types examined, suggesting that FGFR3 mutations are restricted to a few tumor types, the evidence to date suggesting that they are very specific to bladder carcinomas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11526491" 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="#54" class="mim-tip-reference" title="Kimura, T., Suzuki, H., Ohashi, T., Kiyota, H., Eto, Y. <strong>The incidence of thanatophoric dysplasia mutations in FGFR3 bladder carcinomas.</strong> Cancer 92: 2555-2561, 2001. Note: Erratum: Cancer 94: 2117 only, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11745189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11745189</a>] [<a href="https://doi.org/10.1002/1097-0142(20011115)92:10<2555::aid-cncr1607>3.0.co;2-m" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11745189">Kimura et al. (2001)</a> investigated the oncogenic role of mutations in the FGFR3 gene that had been identified in patients with thanatophoric dysplasia. They screened specimens of transitional cell carcinoma of the urinary bladder from 81 patients for TD-causing FGFR3 mutations. Point mutations were detected in 25 of 81 carcinomas. The incidence of TD mutations was significantly higher in low-grade or superficial tumors than in high-grade or muscle-invasive tumors. These findings indicated that TD mutations in the FGFR3 gene do not cause disease progression of bladder carcinoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11745189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="Goriely, A., Hansen, R. M. S., Taylor, I. B., Olesen, I. A., Jacobsen, G. K., McGowan, S. J., Pfeifer, S. P., McVean, G. A. T., Rajpert-De Meyts, E., Wilkie, A. O. M. <strong>Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors.</strong> Nature Genet. 41: 1247-1252, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19855393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19855393</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19855393[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.470" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19855393">Goriely et al. (2009)</a> screened 30 spermatocytic seminomas (see <a href="/entry/273300">273300</a>) for oncogenic mutations in 17 genes and identified 2 mutations in FGFR3 (both K650E, <a href="#0004">134934.0004</a>, which causes thanatophoric dysplasia in the germline) and 5 mutations in HRAS (<a href="/entry/190020">190020</a>). Massively parallel sequencing of sperm DNA showed that levels of the FGFR3 mutation increase with paternal age and that the mutation spectrum at the lys650 codon is similar to that observed in bladder cancer. Most spermatocytic seminomas showed increased immunoreactivity for FGFR3 and/or HRAS. <a href="#31" class="mim-tip-reference" title="Goriely, A., Hansen, R. M. S., Taylor, I. B., Olesen, I. A., Jacobsen, G. K., McGowan, S. J., Pfeifer, S. P., McVean, G. A. T., Rajpert-De Meyts, E., Wilkie, A. O. M. <strong>Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors.</strong> Nature Genet. 41: 1247-1252, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19855393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19855393</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19855393[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.470" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19855393">Goriely et al. (2009)</a> proposed that the paternal age effect mutations activate a common 'selfish' pathway supporting proliferation in the testis, leading to diverse phenotypes in the next generation including fetal lethality, congenital syndromes, and cancer predisposition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19855393" 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="#109" class="mim-tip-reference" title="Singh, D., Chan, J. M., Zoppoli, P., Niola, F., Sullivan, R., Castano, A., Liu, E. M., Reichel, J., Porrati, P., Pellegatta, S., Qiu, K., Gao, Z., and 12 others. <strong>Transforming fusions of FGFR and TACC genes in human glioblastoma.</strong> Science 337: 1231-1235, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22837387/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22837387</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22837387[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1220834" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22837387">Singh et al. (2012)</a> reported that a small subset of glioblastoma multiforme tumors (GBMs; <a href="/entry/137800">137800</a>) (3.1%; 3 of 97 tumors examined) harbors oncogenic chromosomal translocations that fuse in-frame the tyrosine kinase coding domains of fibroblast growth factor receptor (FGFR) genes FGFR1 (<a href="/entry/136350">136350</a>) or FGFR3 to the transforming acidic coiled-coil (TACC) coding domains of TACC1 (<a href="/entry/605301">605301</a>) or TACC3 (<a href="/entry/605303">605303</a>), respectively. The FGFR-TACC fusion protein displayed oncogenic activity when introduced into astrocytes or stereotactically transduced in the mouse brain. The fusion protein, which localizes to mitotic spindle poles, has constitutive kinase activity and induces mitotic and chromosomal segregation defects and triggers aneuploidy. Inhibition of FGFR kinase corrected the aneuploidy, and oral administration of an FGFR inhibitor prolonged survival of mice harboring intracranial FGFR3-TACC3-initiated glioma. <a href="#109" class="mim-tip-reference" title="Singh, D., Chan, J. M., Zoppoli, P., Niola, F., Sullivan, R., Castano, A., Liu, E. M., Reichel, J., Porrati, P., Pellegatta, S., Qiu, K., Gao, Z., and 12 others. <strong>Transforming fusions of FGFR and TACC genes in human glioblastoma.</strong> Science 337: 1231-1235, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22837387/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22837387</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22837387[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1220834" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22837387">Singh et al. (2012)</a> concluded that FGFR-TACC fusions could potentially identify a subset of GBM patients who would benefit from targeted FGFR kinase inhibition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22837387" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Frattini, V., Pagnotta, S. M., Tala, Fan, J. J., Russo, M. V., Lee, S. B., Garofano, L., Zhang, J., Shi, P., Lewis, G., Sanson, H., Frederick, V., and 11 others. <strong>A metabolic function of FGFR3-TACC3 gene fusions in cancer.</strong> Nature 553: 222-227, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29323298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29323298</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29323298[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature25171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29323298">Frattini et al. (2018)</a> demonstrated that human tumors with FGFR3-TACC3 fusions cluster within transcriptional subgroups that are characterized by the activation of mitochondrial functions. FGFR3-TACC3 activates oxidative phosphorylation and mitochondrial biogenesis and induces sensitivity to inhibitors of oxidative metabolism. Phosphorylation of the phosphopeptide PIN4 (<a href="/entry/300252">300252</a>) is an intermediate step in the signaling pathway of the activation of mitochondrial metabolism. The FGFR3-TACC3-PIN4 axis triggers the biogenesis of peroxisomes and the synthesis of new proteins. The anabolic response converges on the PGC1-alpha (<a href="/entry/604517">604517</a>) coactivator through the production of intracellular reactive oxygen species, which enables mitochondrial respiration and tumor growth. <a href="#27" class="mim-tip-reference" title="Frattini, V., Pagnotta, S. M., Tala, Fan, J. J., Russo, M. V., Lee, S. B., Garofano, L., Zhang, J., Shi, P., Lewis, G., Sanson, H., Frederick, V., and 11 others. <strong>A metabolic function of FGFR3-TACC3 gene fusions in cancer.</strong> Nature 553: 222-227, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29323298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29323298</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29323298[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature25171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29323298">Frattini et al. (2018)</a> concluded that their data illustrated the oncogenic circuit engaged by FGFR3-TACC3 and showed that FGFR3-TACC3-positive tumors rely on mitochondrial respiration, highlighting this pathway as a therapeutic opportunity for the treatment of tumors with FGFR3-TACC3 fusions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29323298" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#19" class="mim-tip-reference" title="Colvin, J. S., Bohne, B. A., Harding, G. W., McEwen, D. G., Ornitz, D. M. <strong>Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3.</strong> Nature Genet. 12: 390-397, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8630492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8630492</a>] [<a href="https://doi.org/10.1038/ng0496-390" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8630492">Colvin et al. (1996)</a> reported the findings in mice homozygous for a targeted disruption of Fgfr3. Skeletal defects included kyphosis, scoliosis, crooked tails, and curvature and overgrowth of long bones and vertebrae. Contrasts between the skeletal phenotype of the mice and achondroplasia suggested to the authors that activation of FGFR3 may cause achondroplasia. Furthermore, the mice showed defects of the inner ear, including failure of pillar cell differentiation and tunnel of Corti formation, resulting in profound deafness. The results demonstrated that Fgfr3 is essential for normal endochondral ossification and inner ear development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8630492" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Deng, C., Wynshaw-Boris, A., Zhou, F., Kuo, A., Leder, P. <strong>Fibroblast growth factor receptor 3 is a negative regulator of bone growth.</strong> Cell 84: 911-921, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8601314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8601314</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81069-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8601314">Deng et al. (1996)</a> reported studies in mice made FGFR3 deficient by targeted disruption in the Fgfr3 gene by homologous recombination. Fgfr3 +/- mice showed no phenotypic abnormalities. Fgfr -/- mice had phenotypic effects restricted to bones that arise by endochondral ossification, i.e., increased length of the vertebral column and long bones occurred. Histologic studies revealed cellular expansion, involving hypertrophic chondrocytes, in the growth plates of vertebrae and long bones of mutant homozygotes. <a href="#21" class="mim-tip-reference" title="Deng, C., Wynshaw-Boris, A., Zhou, F., Kuo, A., Leder, P. <strong>Fibroblast growth factor receptor 3 is a negative regulator of bone growth.</strong> Cell 84: 911-921, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8601314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8601314</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81069-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8601314">Deng et al. (1996)</a> proposed that the function of FGFR3 is to limit osteogenesis. They noted that the recessive loss-of-function mutation in Fgfr3 -/- mice produces a phenotype that is the opposite of that observed in achondroplasia and thanatophoric dwarfism. They proposed that the FGFR3 mutations in these disorders lead to constitutive activation (ligand independent activation) of the receptor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8601314" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To study the function of FGFR3 in bone growth and to create animal models for the FGFR3-related inherited skeletal disorders, <a href="#59" class="mim-tip-reference" title="Li, C., Chen, L., Iwata, T., Kitagawa, M., Fu, X.-Y., Deng, C.-X. <strong>A Lys644Glu substitution in fibroblast growth factor receptor 3 (FGFR3) causes dwarfism in mice by activation of STATs and ink4 cell cycle inhibitors.</strong> Hum. Molec. Genet. 8: 35-44, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887329</a>] [<a href="https://doi.org/10.1093/hmg/8.1.35" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9887329">Li et al. (1999)</a> introduced a lys644-to-glu (K644E) point mutation, which corresponded to the lys650-to-glu mutation (K650E; <a href="#0004">134934.0004</a>) found in TD2 patients, into the murine Fgfr3 gene using a knockin approach. They found that in mice the lys644-to-glu mutation resulted in retarded endochondral bone growth with its severity directly linked to the expression level of the mutated Fgfr3. Mice heterozygous for the mutation expressed the mutant allele at approximately 20% of the wildtype level and exhibited a mild bone dysplasia. However, when the copy number of the mutant increased from 1 to 2 (homozygosity), the retardation of bone growth became more severe and showed phenotypes resembling those of achondroplasia patients, characterized by dramatically reduced proliferation of growth plate cartilage, macrocephaly, and shortening of the long bones, which was most pronounced in the femur. Molecular analysis showed that expression of the mutant receptor caused the activation of Stat1 (<a href="/entry/600555">600555</a>), Stat5a (<a href="/entry/601511">601511</a>), and Stat5b, and the upregulation of p16 (<a href="/entry/600160">600160</a>), p18 (<a href="/entry/603369">603369</a>), and p19 (<a href="/entry/600927">600927</a>) cell cycle inhibitors, leading to dramatic expansion of the resting zone of chondrocytes at the expense of the proliferating chondrocytes. The findings provided direct genetic evidence that point mutations in FGFR3 cause human skeletal dysplasias and uncovered a mechanism through which the FGFR3 signals regulate bone growth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9887329" 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="#47" class="mim-tip-reference" title="Iwata, T., Chen, L., Li, C., Ovchinnikov, D. A., Behringer, R. R., Francomano, C. A., Deng, C.-X. <strong>A neonatal lethal mutation in FGFR3 uncouples proliferation and differentiation of growth plate chondrocytes in embryos.</strong> Hum. Molec. Genet. 9: 1603-1613, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10861287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10861287</a>] [<a href="https://doi.org/10.1093/hmg/9.11.1603" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10861287">Iwata et al. (2000)</a> generated a mouse model with the Fgfr3 K644E mutation, which in humans results in thanatophoric dysplasia type II (TD2). Long-bone abnormalities were identified as early as E14, during initiation of endochondral ossification. Increased expression of Patched (<a href="/entry/601309">601309</a>) was observed, independent of unaltered expression of parathyroid hormone-related peptide receptor (<a href="/entry/168468">168468</a>) and Indian Hedgehog (Ihh; <a href="/entry/600726">600726</a>), suggesting a new regulatory role for Fgfr3 in embryos. The mutation enhanced chondrocyte proliferation during early embryonic skeletal development, in contrast to previous reports that showed decreased proliferation in postnatal-onset dwarf mice with activating Fgfr3 mutations. Additionally, suppressed chondrocyte differentiation was observed throughout the embryonic stages, suggesting that decreased differentiation is the primary cause of retarded longitudinal bone growth in TDII. The authors hypothesized that signaling through Fgfr3 both promotes and inhibits chondrocyte proliferation, depending on the time during development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10861287" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Chen, L., Li, C., Qiao, W., Xu, X., Deng, C. <strong>A ser365-cys mutation of fibroblast growth factor receptor 3 in mouse downregulates Ihh/PTHrP signals and causes severe achondroplasia.</strong> Hum. Molec. Genet. 10: 457-465, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11181569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11181569</a>] [<a href="https://doi.org/10.1093/hmg/10.5.457" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11181569">Chen et al. (2001)</a> engineered a transgenic mouse with a ser365-to-cys substitution in Fgfr3, which is equivalent to a human mutation causing thanatophoric dysplasia type I (S371C; <a href="#0006">134934.0006</a>). The mutant mice exhibited shortened limbs as a result of markedly reduced proliferation and impaired differentiation of growth plate chondrocytes. The receptor-activating mutation also resulted in downregulation of expression of Ihh and parathyroid hormone-related protein (PTHRP) receptor genes. Interactions between Fgfr3- and PTHRP-receptor-mediated signals during endochondral ossification were examined in cultured embryonic metatarsal bones. Consistent with the in vivo observations, Fgf2 inhibited bone growth in culture and induced downregulation of Ihh and PTHRP receptor gene expression. Furthermore, PTHRP partially reversed the inhibition of long bone growth caused by activation of Fgfr3; however, it impaired the differentiation of chondrocytes in an Fgfr3-independent manner. The authors hypothesized that Fgfr3 and Ihh-PTHRP signals may be transmitted by 2 interacting parallel pathways that mediate both overlapping and distinct functions during endochondral ossification. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11181569" 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="#48" class="mim-tip-reference" title="Iwata, T., Li, C.-L., Deng, C.-X., Francomano, C. A. <strong>Highly activated Fgfr3 with the K644M mutation causes prolonged survival in severe dwarf mice.</strong> Hum. Molec. Genet. 10: 1255-1264, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11406607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11406607</a>] [<a href="https://doi.org/10.1093/hmg/10.12.1255" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11406607">Iwata et al. (2001)</a> introduced the murine equivalent (K644M) of the human SADDAN point mutation (K650M; <a href="#0015">134934.0015</a>) into the mouse Fgfr3 gene. Heterozygous mutant mice showed a phenotype similar to human SADDAN, e.g., the majority of the SADDAN mice survived the perinatal period. The long bone abnormalities in SADDAN mice were milder than the TDII model. In addition, overgrowth of the cartilaginous tissues was observed in the rib cartilage, trachea, and nasal septum. Unlike the TDII model, FGF ligands at low concentrations differentially activated Map kinase in primary chondrocyte cultures from wildtype and SADDAN mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11406607" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To investigate the effect of the Fgfr3 K644E mutation on CNS development, <a href="#62" class="mim-tip-reference" title="Lin, T., Sandusky, S. B., Xue, H., Fishbein, K. W., Spencer, R. G., Rao, M. S., Francomano, C. A. <strong>A central nervous system specific mouse model for thanatophoric dysplasia type II.</strong> Hum. Molec. Genet. 12: 2863-2871, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12966031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12966031</a>] [<a href="https://doi.org/10.1093/hmg/ddg309" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12966031">Lin et al. (2003)</a> generated tissue-specific TDII mice by crossing K644E transgenic mice with CNS-specific Nestin-cre (NES; <a href="/entry/600915">600915</a>) or cartilage-specific Col2a1-cre (COL2A1; <a href="/entry/120140">120140</a>) mice. CNS-specific neonates did not demonstrate a profound skeletal phenotype; however, many pups exhibited round heads. MRI and histochemical analysis illustrated asymmetric changes in cortical thickness and cerebellar abnormalities in these mice, which correlated with brain abnormalities observed in human TDII patients and which were not seen in cartilage-specific mice. Upon examination of the spinal cords of adult CNS-specific mice, premature differentiation of oligodendrocyte progenitors was observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12966031" 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 a combination of imaging, classic histology and molecular cell biology, <a href="#126" class="mim-tip-reference" title="Valverde-Franco, G., Liu, H., Davidson, D., Chai, S., Valderrama-Carvajal, H., Goltzman, D., Ornitz, D. M., Henderson, J. E. <strong>Defective bone mineralization and osteopenia in young adult FGFR3 -/- mice.</strong> Hum. Molec. Genet. 13: 271-284, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14681299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14681299</a>] [<a href="https://doi.org/10.1093/hmg/ddh034" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14681299">Valverde-Franco et al. (2004)</a> showed that young adult Fgfr3 -/- mice are osteopenic due to reduced cortical bone thickness and defective trabecular bone mineralization. The reduction in mineralized bone and lack of trabecular connectivity observed by microcomputed tomography were confirmed in histologic and histomorphometric analyses, which revealed a significant decrease in calcein labeling of mineralizing surfaces and a significant increase in osteoid in the long bones of 4-month-old Fgfr3 -/- mice. These alterations were associated with increased staining for recognized markers of differentiated osteoblasts and increased numbers of tartrate-resistant acid phosphatase-positive osteoclasts. Primary cultures of adherent bone marrow-derived cells from Fgfr3 -/- mice expressed markers of differentiated osteoblasts but developed fewer mineralized nodules than Fgfr3 +/+ cultures of the same age. <a href="#126" class="mim-tip-reference" title="Valverde-Franco, G., Liu, H., Davidson, D., Chai, S., Valderrama-Carvajal, H., Goltzman, D., Ornitz, D. M., Henderson, J. E. <strong>Defective bone mineralization and osteopenia in young adult FGFR3 -/- mice.</strong> Hum. Molec. Genet. 13: 271-284, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14681299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14681299</a>] [<a href="https://doi.org/10.1093/hmg/ddh034" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14681299">Valverde-Franco et al. (2004)</a> hypothesized a role for FGFR3 in postnatal bone growth and remodeling, and suggested that it may be a potential therapeutic agent for osteopenic disorders and those associated with defective bone mineralization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14681299" 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>C-type natriuretic peptide (CNP; <a href="/entry/600296">600296</a>) regulates endochondral bone growth through guanylyl cyclase type B. <a href="#136" class="mim-tip-reference" title="Yasoda, A., Komatsu, Y., Chusho, H., Miyazawa, T., Ozasa, A., Miura, M., Kurihara, T., Rogi, T., Tanaka, S., Suda, M., Tamura, N., Ogawa, Y., Nakao, K. <strong>Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway.</strong> Nature Med. 10: 80-86, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14702637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14702637</a>] [<a href="https://doi.org/10.1038/nm971" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14702637">Yasoda et al. (2004)</a> showed that targeted overexpression of CNP in chondrocytes counteracted dwarfism in a mouse model of achondroplasia with activated FGFR3 in cartilage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14702637" 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="#63" class="mim-tip-reference" title="Logie, A., Dunois-Larde, C., Rosty, C., Levrel, O., Blanche, M., Ribeiro, A., Gasc, J.-M., Jorcano, J., Werner, S., Sastre-Garau, X., Thiery, J. P., Radvanyi, F. <strong>Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans.</strong> Hum. Molec. Genet. 14: 1153-1160, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15772091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15772091</a>] [<a href="https://doi.org/10.1093/hmg/ddi127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15772091">Logie et al. (2005)</a> targeted an activated FGFR3 mutant, S249C (<a href="#0013">134934.0013</a>), to basal cells of the epidermis of mice. FGFR3-mutant mice developed benign epidermal tumors with no sign of malignancy. These skin lesions had features in common with acanthosis nigricans and other benign human skin tumors, including seborrheic keratosis, one of the most common benign epidermal tumors in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15772091" 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 PC12 cell lines stably expressing inducible mutant receptors containing the TDII mutation, K650E (<a href="#0004">134934.0004</a>), <a href="#80" class="mim-tip-reference" title="Nowroozi, N., Raffioni, S., Wang, T., Apostol, B. L., Bradshaw, R. A., Thompson, L. M. <strong>Sustained ERK1/2 but not STAT1 or 3 activation is required for thanatophoric dysplasia phenotypes in PC12 cells.</strong> Hum. Molec. Genet. 14: 1529-1538, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15843401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15843401</a>] [<a href="https://doi.org/10.1093/hmg/ddi161" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15843401">Nowroozi et al. (2005)</a> observed sustained activation of Erk1/2 (see <a href="/entry/601795">601795</a>) and activation of Stat1 and Stat3 (<a href="/entry/102582">102582</a>), but not Stat5a (<a href="/entry/601511">601511</a>), in the absence of ligand. This activation led to neurite outgrowth, a phenotypic readout of constitutive receptor activity; sustained Erk1/2 activity was required for this ligand-independent differentiation. Silencing of Stat1 or Stat3 independently or in combination had no significant effect on ligand-independent neurite outgrowth, Erk1/2 activation, or p21 (CDKN1A; <a href="/entry/116899">116899</a>) protein levels. <a href="#80" class="mim-tip-reference" title="Nowroozi, N., Raffioni, S., Wang, T., Apostol, B. L., Bradshaw, R. A., Thompson, L. M. <strong>Sustained ERK1/2 but not STAT1 or 3 activation is required for thanatophoric dysplasia phenotypes in PC12 cells.</strong> Hum. Molec. Genet. 14: 1529-1538, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15843401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15843401</a>] [<a href="https://doi.org/10.1093/hmg/ddi161" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15843401">Nowroozi et al. (2005)</a> proposed a model in which sustained activation of ERK1/2 is a key regulator of the increased transition to hypertrophic differentiation of the growth plate, whereas activation of STAT1 and STAT3 is not required. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15843401" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Eswarakumar, V. P., Schlessinger, J. <strong>Skeletal overgrowth is mediated by deficiency in a specific isoform of fibroblast growth factor receptor 3.</strong> Proc. Nat. Acad. Sci. 104: 3937-3942, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360456</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360456[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0700012104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17360456">Eswarakumar and Schlessinger (2007)</a> generated mice with selective inactivation of the Fgfr3b and Fgfr3c isoforms, respectively. Fgfr3c-null mice showed dramatic overgrowth of the axial and appendicular skeleton and other abnormalities resulting from strong stimulation of chondrocyte proliferation in the growth plates. These mice also showed decreased bone mineral density. In contrast, Fgfr3b-null mice showed no apparent phenotype and had bone mineral density similar to wildtype mice. The findings demonstrated that the mesenchymal Fgfr3c isoform is responsible for controlling chondrocyte proliferation and differentiation in skeletal development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17360456" 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="#66" class="mim-tip-reference" title="Mansour, S. L., Twigg, S. R. F., Freeland, R. M., Wall, S. A., Li, C., Wilkie, A. O. M. <strong>Hearing loss in a mouse model of Muenke syndrome.</strong> Hum. Molec. Genet. 18: 43-50, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18818193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18818193</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18818193[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/ddn311" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18818193">Mansour et al. (2009)</a> generated mice homozygous and heterozygous for a P244R mutation in the Fgfr3 gene, which is the equivalent of the human P250R mutation, as a mouse model of Muenke syndrome (<a href="/entry/602849">602849</a>). Fgfr3 P244R/+ and P244R/P244R mice showed dominant, fully penetrant low frequency hearing loss that was similar but more severe than in Muenke syndrome patients. Mouse hearing loss correlated with an alteration in the fate of supporting cells (Deiters-to-pillar cells) along the entire length of the cochlear duct, especially at the apical or low frequency end. There was excess outer hair cell development in the apical region. Hearing loss was dosage sensitive as homozygotes were more severely affected than heterozygotes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18818193" 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 microcomputed tomography and histomorphometric analyses, <a href="#112" class="mim-tip-reference" title="Su, N., Sun, Q., Li, C., Lu, X., Qi, H., Chen, S., Yang, J., Du, X., Zhao, L., He, Q., Jin, M., Shen, Y., Chen, D., Chen, L. <strong>Gain-of-function mutation in FGFR3 in mice leads to decreased bone mass by affecting both osteoblastogenesis and osteoclastogenesis.</strong> Hum. Molec. Genet. 19: 1199-1210, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20053668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20053668</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20053668[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/ddp590" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20053668">Su et al. (2010)</a> found that 2-month-old Fgfr3(G369C/+) mice (mouse model mimicking human ACH) showed decreased bone mass due to reduced trabecular bone volume and bone mineral density, defect in bone mineralization, and increased osteoclast numbers and activity. Compared with primary cultures of bone marrow stromal cells (BMSCs) from wildtype mice, Fgfr3(G369C/+) cultures showed decreased cell proliferation, increased osteogenic differentiation including upregulation of alkaline phosphatase activity and expression of osteoblast marker genes, and reduced bone matrix mineralization. <a href="#112" class="mim-tip-reference" title="Su, N., Sun, Q., Li, C., Lu, X., Qi, H., Chen, S., Yang, J., Du, X., Zhao, L., He, Q., Jin, M., Shen, Y., Chen, D., Chen, L. <strong>Gain-of-function mutation in FGFR3 in mice leads to decreased bone mass by affecting both osteoblastogenesis and osteoclastogenesis.</strong> Hum. Molec. Genet. 19: 1199-1210, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20053668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20053668</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20053668[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/ddp590" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20053668">Su et al. (2010)</a> suggested that decreased cell proliferation and enhanced osteogenic differentiation observed in Fgfr3(G369C/+) BMSCs may be caused by upregulation of p38 (MAPK14; <a href="/entry/600289">600289</a>) phosphorylation, and that enhanced Erk1/2 (MAPK3; <a href="/entry/601795">601795</a>) activity may be responsible for the impaired bone matrix mineralization. In vitro osteoclast formation and bone resorption assays demonstrated that osteoclast numbers and bone resorption area were increased in cultured bone marrow cells derived from Fgfr3(G369C/+) mice. <a href="#112" class="mim-tip-reference" title="Su, N., Sun, Q., Li, C., Lu, X., Qi, H., Chen, S., Yang, J., Du, X., Zhao, L., He, Q., Jin, M., Shen, Y., Chen, D., Chen, L. <strong>Gain-of-function mutation in FGFR3 in mice leads to decreased bone mass by affecting both osteoblastogenesis and osteoclastogenesis.</strong> Hum. Molec. Genet. 19: 1199-1210, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20053668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20053668</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20053668[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/ddp590" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20053668">Su et al. (2010)</a> concluded that gain-of-function mutations in FGFR3 may lead to decreased bone mass by regulating both osteoblast and osteoclast activities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20053668" 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="#135" class="mim-tip-reference" title="Yamashita, A., Morioka, M., Kishi, H., Kimura, T., Yahara, Y., Okada, M., Fujita, K., Sawai, H., Ikegawa, S., Tsumaki, N. <strong>Statin treatment rescues FGFR3 skeletal dysplasia phenotypes.</strong> Nature 513: 507-511, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25231866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25231866</a>] [<a href="https://doi.org/10.1038/nature13775" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25231866">Yamashita et al. (2014)</a> showed that statin treatment could rescue patient-specific induced pluripotent stem cells (iPSCs) and the chondrodysplasia phenotype of Fgfr3(Ach) transgenic mice that expressed an activated FGFR3 containing the G380R mutation (<a href="#0001">134934.0001</a>) in the growth plate (<a href="#75" class="mim-tip-reference" title="Naski, M. C., Colvin, J. S., Coffin, J. D., Ornitz, D. M. <strong>Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3.</strong> Development 125: 4977-4988, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9811582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9811582</a>] [<a href="https://doi.org/10.1242/dev.125.24.4977" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9811582">Naski et al., 1998</a>). <a href="#135" class="mim-tip-reference" title="Yamashita, A., Morioka, M., Kishi, H., Kimura, T., Yahara, Y., Okada, M., Fujita, K., Sawai, H., Ikegawa, S., Tsumaki, N. <strong>Statin treatment rescues FGFR3 skeletal dysplasia phenotypes.</strong> Nature 513: 507-511, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25231866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25231866</a>] [<a href="https://doi.org/10.1038/nature13775" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25231866">Yamashita et al. (2014)</a> converted fibroblasts from patients with thanatophoric dysplasia type I (TD1; <a href="/entry/187600">187600</a>) and achondroplasia into iPSCs. The chondrogenic differentiation of TD1 iPSCs and achondroplasia iPSCs resulted in the formation of degraded cartilage. <a href="#135" class="mim-tip-reference" title="Yamashita, A., Morioka, M., Kishi, H., Kimura, T., Yahara, Y., Okada, M., Fujita, K., Sawai, H., Ikegawa, S., Tsumaki, N. <strong>Statin treatment rescues FGFR3 skeletal dysplasia phenotypes.</strong> Nature 513: 507-511, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25231866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25231866</a>] [<a href="https://doi.org/10.1038/nature13775" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25231866">Yamashita et al. (2014)</a> found that statins could correct the degraded cartilage in both chondrogenically differentiated TD1 and achondroplasia iPSCs. Treatment of Fgfr3(Ach) model mice with statin led to a significant recovery of bone growth. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25231866+9811582" 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>38 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/134934" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=134934[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 ACHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
NEVUS, EPIDERMAL, SOMATIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, GLY380ARG, 1138G-A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28931614 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28931614;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/rs28931614?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=rs28931614" 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=rs28931614" 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=RCV000017724 OR RCV000017763 OR RCV000029207 OR RCV000255750 OR RCV000763121 OR RCV001266979 OR RCV001807732 OR RCV002276551 OR RCV003227605 OR RCV004545731 OR RCV004783725 OR RCV004798732" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017724, RCV000017763, RCV000029207, RCV000255750, RCV000763121, RCV001266979, RCV001807732, RCV002276551, RCV003227605, RCV004545731, RCV004783725, RCV004798732" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017724...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In achondroplasia (ACH; <a href="/entry/100800">100800</a>), codon 380 in the FGFR3 gene is changed from GGG to AGG or CGG (<a href="#105" class="mim-tip-reference" title="Shiang, R., Thompson, L. M., Zhu, Y.-Z., Church, D. M., Fielder, T. J., Bocian, M., Winokur, S. T., Wasmuth, J. J. <strong>Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.</strong> Cell 78: 335-342, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7913883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7913883</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90302-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7913883">Shiang et al., 1994</a>). Codon 379 is TAC (tyr). <a href="#97" class="mim-tip-reference" title="Rousseau, F., Bonaventure, J., Legeai-Mallet, L., Pelet, A., Rozet, J.-M., Maroteaux, P., Le Merrer, M., Munnich, A. <strong>Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.</strong> Nature 371: 252-254, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8078586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8078586</a>] [<a href="https://doi.org/10.1038/371252a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8078586">Rousseau et al. (1994)</a> found the gly380-to-arg mutation in all 23 cases of achondroplasia studied (17 sporadic and 6 familial). Twenty-two of the 23 probands had the G-to-A transition; only 1 had the G-to-C transversion (<a href="#0002">134934.0002</a>). See also <a href="#45" class="mim-tip-reference" title="Ikegawa, S., Fukushima, Y., Isomura, M., Takada, F., Nakamura, Y. <strong>Mutations of the fibroblast growth factor receptor-3 gene in one familial and six sporadic cases of achondroplasia in Japanese patients.</strong> Hum. Genet. 96: 309-311, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7649548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7649548</a>] [<a href="https://doi.org/10.1007/BF00210413" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7649548">Ikegawa et al. (1995)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7649548+7913883+8078586" 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>Nucleotide 1138 of the FGFR3 gene may be one of the most mutable bases in the human genome. <a href="#133" class="mim-tip-reference" title="Wilkie, A. O. M. <strong>Craniosynostosis: genes and mechanisms.</strong> Hum. Molec. Genet. 6: 1647-1656, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9300656/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9300656</a>] [<a href="https://doi.org/10.1093/hmg/6.10.1647" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9300656">Wilkie (1997)</a> commented that it seems unlikely to be coincidental that the 3 highest germline point mutation rates described in the human (elevated approximately 1000-fold over background) all concern FGFRs: G380R and P250R in FGFR3 (<a href="#0014">134934.0014</a>) and S252W in FGFR2 (<a href="/entry/176943#0010">176943.0010</a>). These 3 mutations result in achondroplasia, Muenke nonsyndromic coronal craniosynostosis, and Apert syndrome (<a href="/entry/101200">101200</a>), respectively. Increased paternal age associated with achondroplasia and Apert syndrome has long been known, and an exclusively paternal origin of mutation was shown in studies of 57 Apert syndrome patients by <a href="#70" class="mim-tip-reference" title="Moloney, D. M., Slaney, S. F., Oldridge, M., Wall, S. A., Sahlin, P., Stenman, G., Wilkie, A. O. M. <strong>Exclusive paternal origin of new mutations in Apert syndrome.</strong> Nature Genet. 13: 48-53, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673103</a>] [<a href="https://doi.org/10.1038/ng0596-48" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8673103">Moloney et al. (1996)</a> and in 10 achondroplasia patients by <a href="#116" class="mim-tip-reference" title="Szabo, J., Bellus, G. A., Kaitila, I., Francomano, C. A. <strong>Fibroblast growth factor receptor 3 (FGFR3) mutations in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome. (Abstract)</strong> Am. J. Hum. Genet. 59 (suppl.): A287 only, 1996."None>Szabo et al. (1996)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9300656+8673103" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 24-year-old woman whose fetus was suspected by ultrasonography to have a short-limb disorder, <a href="#101" class="mim-tip-reference" title="Saito, H., Sekizawa, A., Morimoto, T., Suzuki, M., Yanaihara, T. <strong>Prenatal DNA diagnosis of a single-gene disorder from maternal plasma.</strong> Lancet 356: 1170 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11030304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11030304</a>] [<a href="https://doi.org/10.1016/S0140-6736(00)02767-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11030304">Saito et al. (2000)</a> made the diagnosis of achondroplasia by identifying the 1138G-A mutation using PCR with specific primers. Restriction fragment length polymorphism analysis of PCR products was done with SfcI. DNA for the studies was extracted from maternal plasma; the mutation was not found in maternal leukocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11030304" 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="#127" class="mim-tip-reference" title="Van Esch, H., Fryns, J. P. <strong>Acanthosis nigricans in a boy with achondroplasia due to the classical gly380arg mutation in FGFR3.</strong> Genet. Counsel. 15: 375-377, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15517832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15517832</a>]" pmid="15517832">Van Esch and Fryns (2004)</a> described acanthosis nigricans in a 9-year-old boy with achondroplasia due to the classic gly380-to-arg mutation in FGFR3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15517832" 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>Affected sibs with classic achondroplasia but unaffected parents were described by <a href="#39" class="mim-tip-reference" title="Henderson, S., Sillence, D., Loughlin, J., Bennetts, B., Sykes, B. <strong>Germline and somatic mosaicism in achondroplasia.</strong> J. Med. Genet. 37: 956-958, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11186939/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11186939</a>] [<a href="https://doi.org/10.1136/jmg.37.12.956" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11186939">Henderson et al. (2000)</a> and <a href="#110" class="mim-tip-reference" title="Sobetzko, D., Braga, S., Rudeberg, A., Superti-Furga, A. <strong>Achondroplasia with the FGFR3 1138g-a (G380R) mutation in two sibs sharing a 4p haplotype derived from their unaffected father. (Letter)</strong> J. Med. Genet. 37: 958-959, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11186940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11186940</a>] [<a href="https://doi.org/10.1136/jmg.37.12.958" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11186940">Sobetzko et al. (2000)</a>. Both were apparent instances of germinal mosaicism. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11186940+11186939" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a sperm study of 97 men aged 22 to 80 years, <a href="#134" class="mim-tip-reference" title="Wyrobek, A. J., Eskenazi, B., Young, S., Arnheim, N., Tiemann-Boege, I., Jabs, E. W., Glaser, R. L., Pearson, F. S., Evenson, D. <strong>Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm.</strong> Proc. Nat. Acad. Sci. 103: 9601-9606, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16766665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16766665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16766665[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0506468103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16766665">Wyrobek et al. (2006)</a> found associations between increased age and genomic defects as measured by the DNA fragmentation index and increased age and the FGFR3 1138G-A mutation without evidence for an age threshold. However, there was no association between age and frequency of sperm with immature chromatin, aneuploidies/diploidies, FGFR2 mutations causing Apert syndrome, or sex ratio. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16766665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 sibs who were the product of the first and third pregnancies of healthy nonconsanguineous parents, <a href="#77" class="mim-tip-reference" title="Natacci, F., Baffico, M., Cavallari, U., Bedeschi, M. F., Mura, I., Paffoni, A., Setti, P. L., Baldi, M., Lalatta, F. <strong>Germline mosaicism in achondroplasia detected in sperm DNA of the father of three affected sibs.</strong> Am. J. Med. Genet. 146A: 784-786, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18266238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18266238</a>] [<a href="https://doi.org/10.1002/ajmg.a.32228" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18266238">Natacci et al. (2008)</a> identified heterozygosity for the G380R mutation in the FGFR3 gene. The mutation was not found in lymphocytic DNA from the parents; however, DNA analysis of a sperm sample from the 37-year-old father showed the G380R mutation. The authors stated that this was the second reported case of germinal mosaicism causing recurrent achondroplasia in a subsequent conception. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18266238" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#36" class="mim-tip-reference" title="He, L., Horton, W., Hristova, K. <strong>Physical basis behind achondroplasia, the most common form of human dwarfism.</strong> J. Biol. Chem. 285: 30103-30114, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20624921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20624921</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20624921[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/10.1074/jbc.M109.094086" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20624921">He et al. (2010)</a> found that the G380R mutation within the transmembrane domain of FGFR3 increased the phosphorylation of tyr647 and tyr648 within the FGFR3 catalytic domain in the absence of FGF1 and at low FGF1 concentration. They determined that the increased kinase activity of mutant FGFR3 was due to a conformational change. The amino acids that mediate helix-helix contacts in the wildtype dimer are leu377, val381, phe384, and ile387, whereas the mutant dimer interface is rotated to involve ile376, arg380, phe383, ile387, val390, and thr394. The 2 alanines at position 391 face each other directly in the wildtype structure, but are rotated away from each other in the mutant structure. <a href="#36" class="mim-tip-reference" title="He, L., Horton, W., Hristova, K. <strong>Physical basis behind achondroplasia, the most common form of human dwarfism.</strong> J. Biol. Chem. 285: 30103-30114, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20624921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20624921</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20624921[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/10.1074/jbc.M109.094086" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20624921">He et al. (2010)</a> hypothesized that the rotation at the dimerization interface would induce a concomitant rotation of the catalytic domains with respect to each other and change their kinetics of kinase activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20624921" 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="#37" class="mim-tip-reference" title="He, L., Shobnam, N., Wimley, W. C., Hristova, K. <strong>FGFR3 heterodimerization in achondroplasia, the most common form of human dwarfism.</strong> J. Biol. Chem. 286: 13272-13281, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21324899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21324899</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21324899[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/10.1074/jbc.M110.205583" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21324899">He et al. (2011)</a> showed that the G380R mutation decreased the probability of heterodimer formation between mutant and wildtype subunits at low ligand concentration, but not at high ligand concentration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21324899" 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>Nevus, Epidermal, Somatic</em></strong></p><p>
|
|
<a href="#35" class="mim-tip-reference" title="Hafner, C., van Oers, J. M. M., Vogt, T., Landthaler, M., Stoehr, R., Blaszyk, H., Hofstaedter, F., Zwarthoff, E. C., Hartmann, A. <strong>Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi.</strong> J. Clin. Invest. 116: 2201-2207, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16841094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16841094</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16841094[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/10.1172/JCI28163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16841094">Hafner et al. (2006)</a> analyzed the FGFR3 gene in 39 common epidermal nevi (<a href="/entry/162900">162900</a>) from 33 patients and identified mosaicism for a double mutation in exon 10 of the FGFR3 gene in 1 patient: the G372C mutation (G370C; <a href="#0033">134934.0033</a>) and the G382R mutation. Codons were numbered according to the FGFR3 IIIb isoform. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16841094" 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 ACHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, GLY380ARG, 1138G-C
|
|
</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> rs28931614 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28931614;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/rs28931614?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=rs28931614" 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=rs28931614" 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=RCV000017725 OR RCV000727147 OR RCV000987394 OR RCV004532375 OR RCV004795424" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017725, RCV000727147, RCV000987394, RCV004532375, RCV004795424" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017725...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#97" class="mim-tip-reference" title="Rousseau, F., Bonaventure, J., Legeai-Mallet, L., Pelet, A., Rozet, J.-M., Maroteaux, P., Le Merrer, M., Munnich, A. <strong>Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.</strong> Nature 371: 252-254, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8078586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8078586</a>] [<a href="https://doi.org/10.1038/371252a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8078586">Rousseau et al. (1994)</a> found the gly380-to-arg mutation in all 23 cases of achondroplasia (ACH; <a href="/entry/100800">100800</a>) studied (17 sporadic and 6 familial). Twenty-two of the 23 probands had the G-to-A transition (<a href="#0001">134934.0001</a>); only 1 had the G-to-C transversion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8078586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0003" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 ACHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, GLY375CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs75790268 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs75790268;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=rs75790268" 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=rs75790268" 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=RCV000017727 OR RCV002228031" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017727, RCV002228031" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017727...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#115" class="mim-tip-reference" title="Superti-Furga, A., Eich, G., Bucher, H. U., Wisser, J., Giedion, A., Gitzelmann, R., Steinmann, B. <strong>A glycine 375-to-cysteine substitution in the transmembrane domain of the fibroblast growth factor receptor-3 in a newborn with achondroplasia.</strong> Europ. J. Pediat. 154: 215-219, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7758520/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7758520</a>] [<a href="https://doi.org/10.1007/BF01954274" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7758520">Superti-Furga et al. (1995)</a> found a G375C mutation in a newborn with achondroplasia (ACH; <a href="/entry/100800">100800</a>) born to a 26-year-old mother and a 42-year-old father. The amino acid substitution was due to heterozygosity for a de novo G-to-T transversion at the first position of codon 375. Although the phenotype appeared to be characteristic of achondroplasia, the possibility that differences from classic achondroplasia might be evident at a later age was mentioned. It is of note that this was a twin pregnancy, first demonstrated by ultrasound examination at week 32 of gestation. The previously normal-appearing twin suffered intrauterine death at about week 35 and the achondroplastic twin was delivered by cesarean section. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7758520" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#45" class="mim-tip-reference" title="Ikegawa, S., Fukushima, Y., Isomura, M., Takada, F., Nakamura, Y. <strong>Mutations of the fibroblast growth factor receptor-3 gene in one familial and six sporadic cases of achondroplasia in Japanese patients.</strong> Hum. Genet. 96: 309-311, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7649548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7649548</a>] [<a href="https://doi.org/10.1007/BF00210413" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7649548">Ikegawa et al. (1995)</a> also found the gly375-to-cys mutation in a single case. In 7 Japanese patients with achondroplasia, 6 sporadic cases all showed a G-to-A mutation at codon 380 (<a href="#0001">134934.0001</a>). The single familial case bore a G-to-T transition at codon 375, resulting in substitution of cysteine for glycine; both mother and child were affected. <a href="#78" class="mim-tip-reference" title="Nishimura, G., Fukushima, Y., Ohashi, H., Ikegawa, S. <strong>Atypical radiological findings in achondroplasia with uncommon mutation of the fibroblast growth factor receptor-3 (FGFR-3) gene (gly to cys transition at codon 375). (Letter)</strong> Am. J. Med. Genet. 59: 393-395, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8599370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8599370</a>] [<a href="https://doi.org/10.1002/ajmg.1320590325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8599370">Nishimura et al. (1995)</a> reported the atypical radiologic findings in the patient with the gly375-to-cys mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7649548+8599370" 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="#79" class="mim-tip-reference" title="Nishimura, G., Takada, F. <strong>Another observation of atypical radiologic findings in achondroplasia not due to a common mutation of the FGFR-3 gene: reply to Dr. Gorlin. (Letter)</strong> Am. J. Med. Genet. 70: 203-205, 1997."None>Nishimura and Takada (1997)</a> reported yet another patient with achondroplasia due to the gly375-to-cys mutation of the FGFR3 gene. The patient was a Japanese boy born of healthy, unrelated parents: a 38-year-old father and a 33-year-old mother. Short femurs were detected at 35 weeks' gestation. Although mild micromelia was suspected at birth, radiologic examination was not carried out at that time. Subsequently, rhizomelia became evident, and trident hands were noted. Skeletal survey at age 6 months showed narrow thorax, interpediculate narrowing of the lumbar spine, hypoplastic ilia, and short limbs with mild metaphyseal cupping. The skeletal abnormality was considered milder than those in achondroplasia. At age 8 months, his facial appearance was said not to be typical of achondroplasia; he had neither frontal bossing nor overt midface 'recession.'</p><p><a href="#14" class="mim-tip-reference" title="Chen, L., Adar, R., Yang, X., Monsonego, E. O., Li, C., Hauschka, P. V., Yayon, A., Deng, C.-X. <strong>Gly369-to-cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis.</strong> J. Clin. Invest. 104: 1517-1525, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10587515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10587515</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10587515[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/10.1172/JCI6690" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10587515">Chen et al. (1999)</a> demonstrated that the gly375-to-cys mutation in human FGFR3 causes ligand-independent dimerization and phosphorylation of FGFR3. They also showed that the equivalent substitution at position 369 (gly369 to cys) in mouse Fgfr3 causes dwarfism with features mimicking human achondroplasia. As is the case in humans, homozygous mice were more severely affected than heterozygotes. The resulting mutant mice exhibited macrocephaly and shortened limbs due to retarded endochondral bone growth and premature closure of cranial base synchondroses. Compared with their wildtype littermates, mutant mice growth plates shared an expanded resting zone and narrowed proliferating and hypertrophic zones, which was correlated with the activation of Stat proteins and upregulation of cell cycle inhibitors. Reduced bone density is accompanied by increased activity of osteoclasts and upregulation of genes that are related to osteoblast differentiation, including osteopontin (<a href="/entry/166490">166490</a>), osteonectin (<a href="/entry/182120">182120</a>), and osteocalcin (<a href="/entry/112260">112260</a>). They demonstrated an essential role for FGF/FGFR3 signals in both chondrogenesis and osteogenesis during endochondral ossification. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10587515" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0004" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 THANATOPHORIC DYSPLASIA, TYPE II</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MULTIPLE MYELOMA, SOMATIC, INCLUDED<br />
|
|
SPERMATOCYTIC SEMINOMA, SOMATIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, LYS650GLU
|
|
</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> rs78311289 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs78311289;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/rs78311289?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=rs78311289" 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=rs78311289" 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=RCV000017728 OR RCV000017729 OR RCV000017730 OR RCV000255799 OR RCV003155029 OR RCV003234912 OR RCV003317039 OR RCV004532376 OR RCV005031441" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017728, RCV000017729, RCV000017730, RCV000255799, RCV003155029, RCV003234912, RCV003317039, RCV004532376, RCV005031441" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017728...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Thanatophoric Dysplasia, Type II</em></strong></p><p>
|
|
In 16 individuals with type II thanatophoric dysplasia (TD2; <a href="/entry/187601">187601</a>), <a href="#120" class="mim-tip-reference" title="Tavormina, P. L., Shiang, R., Thompson, L. M., Zhu, Y.-Z., Wilkin, D. J., Lachman, R. S., Wilcox, W. R., Rimoin, D. L., Cohn, D. H., Wasmuth, J. J. <strong>Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3.</strong> Nature Genet. 9: 321-328, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7773297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7773297</a>] [<a href="https://doi.org/10.1038/ng0395-321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7773297">Tavormina et al. (1995)</a> identified a heterozygous 1948A-G mutation in the FGFR3 gene, causing a lys650-to-glu (K650E) substitution in the tyrosine kinase domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7773297" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a review of 91 cases of TD by <a href="#130" class="mim-tip-reference" title="Wilcox, W. R., Tavormina, P. L., Krakow, D., Kitoh, H., Lachman, R. S., Wasmuth, J. J., Thompson, L. M., Rimoin, D. L. <strong>Molecular, radiologic, and histopathologic correlations in thanatophoric dysplasia.</strong> Am. J. Med. Genet. 78: 274-281, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9677066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9677066</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19980707)78:3<274::aid-ajmg14>3.0.co;2-c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9677066">Wilcox et al. (1998)</a>, the K650E mutation was the only cause of TD type II, and occurred in 17 cases (19%). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9677066" 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="#60" class="mim-tip-reference" title="Li, D., Liao, C., Ma, X., Li, Q., Tang, X. <strong>Thanatophoric dysplasia type 2 with encephalocele during the second trimester.</strong> Am. J. Med. Genet. 140A: 1476-1477, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16752380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16752380</a>] [<a href="https://doi.org/10.1002/ajmg.a.31293" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16752380">Li et al. (2006)</a> reported a female fetus with TD2 and occipital encephalocele, in whom they identified the K650E mutation in the FGFR3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16752380" 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="#61" class="mim-tip-reference" title="Lievens, P. M.-J., Liboi, E. <strong>The thanatophoric dysplasia type II mutation hampers complete maturation of fibroblast growth factor receptor 3 (FGFR3), which activates signal transducer and activator of transcription 1 (STAT1) from the endoplasmic reticulum.</strong> J. Biol. Chem. 278: 17344-17349, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12624096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12624096</a>] [<a href="https://doi.org/10.1074/jbc.M212710200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12624096">Lievens and Liboi (2003)</a> found that the K605E mutation hampers complete maturation of FGFR3. The mutation causes the immature phosphorylated FGFR3 intermediate glycomers to activate STAT1 (<a href="/entry/600555">600555</a>) from the endoplasmic reticulum. They suggested that this was the first report of a tyrosine kinase receptor that signals from within the cell in its immature form. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12624096" 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>Multiple Myeloma, Somatic</em></strong></p><p>
|
|
<a href="#16" class="mim-tip-reference" title="Chesi, M., Nardini, E., Brents, L. A., Schrock, E., Ried, T., Kuehl, W. M., Bergsagel, P. L. <strong>Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3.</strong> Nature Genet. 16: 260-264, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9207791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9207791</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9207791[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng0797-260" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9207791">Chesi et al. (1997)</a> found this mutation in cell lines and tumors from cases of multiple myeloma. They proposed that after the illegitimate switch recombination between 4p and 14q as the result of the t(4;14) translocation, somatic mutation during tumor progression generated an FGFR3 protein that was active in the absence of ligand. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9207791" 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>Spermatocytic Seminoma, Somatic</em></strong></p><p>
|
|
<a href="#31" class="mim-tip-reference" title="Goriely, A., Hansen, R. M. S., Taylor, I. B., Olesen, I. A., Jacobsen, G. K., McGowan, S. J., Pfeifer, S. P., McVean, G. A. T., Rajpert-De Meyts, E., Wilkie, A. O. M. <strong>Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors.</strong> Nature Genet. 41: 1247-1252, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19855393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19855393</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19855393[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.470" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19855393">Goriely et al. (2009)</a> screened 30 spermatocytic seminomas (see <a href="/entry/273300">273300</a>) for oncogenic mutations in 17 genes and identified the K650E mutation in FGFR3 in 2 tumors. Massively parallel sequencing of sperm DNA showed that levels of the FGFR3 mutation increase with paternal age and that the mutation spectrum at the lys650 codon is similar to that observed in bladder cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19855393" 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 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MULTIPLE MYELOMA, SOMATIC, INCLUDED<br />
|
|
SKELETAL DYSPLASIA WITH ACANTHOSIS NIGRICANS, INCLUDED<br />
|
|
NEVUS, EPIDERMAL, SOMATIC, INCLUDED<br />
|
|
KERATOSIS, SEBORRHEIC, SOMATIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, ARG248CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121913482 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913482;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=rs121913482" 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=rs121913482" 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=RCV000017731 OR RCV000017732 OR RCV000017733 OR RCV000017734 OR RCV000017735 OR RCV000327823 OR RCV000414822 OR RCV000763118 OR RCV001196297 OR RCV001526641 OR RCV001804739 OR RCV001849270 OR RCV002243648 OR RCV002276552 OR RCV003155030 OR RCV003332082 OR RCV003388567 OR RCV004795425 OR RCV004798733 OR RCV005025063" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017731, RCV000017732, RCV000017733, RCV000017734, RCV000017735, RCV000327823, RCV000414822, RCV000763118, RCV001196297, RCV001526641, RCV001804739, RCV001849270, RCV002243648, RCV002276552, RCV003155030, RCV003332082, RCV003388567, RCV004795425, RCV004798733, RCV005025063" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017731...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Thanatophoric Dysplasia, Type I</em></strong></p><p>
|
|
Of 39 individuals with type I thanatophoric dysplasia (TD1; <a href="/entry/187600">187600</a>), <a href="#120" class="mim-tip-reference" title="Tavormina, P. L., Shiang, R., Thompson, L. M., Zhu, Y.-Z., Wilkin, D. J., Lachman, R. S., Wilcox, W. R., Rimoin, D. L., Cohn, D. H., Wasmuth, J. J. <strong>Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3.</strong> Nature Genet. 9: 321-328, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7773297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7773297</a>] [<a href="https://doi.org/10.1038/ng0395-321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7773297">Tavormina et al. (1995)</a> found an arg248-to-cys mutation resulting from a C-to-T transition at nucleotide 742 in 22 and a ser371-to-cys mutation (<a href="#0006">134934.0006</a>) in 1. Both of these mutations were in the extracellular region of the FGFR3 protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7773297" 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>Although type II thanatophoric dysplasia (<a href="/entry/187601">187601</a>) cases have been found to have a single recurrent K650E change (<a href="#0004">134934.0004</a>), type I cases have different mutations affecting either the extracellular or intracellular domains of FGFR3. However, mutations in the FGFR3 gene were identified in only approximately 60% of the type I TD cases. These findings, and the range of symptoms observed, suggested that type I TD is heterogeneous in genetic background. <a href="#86" class="mim-tip-reference" title="Pokharel, R. K., Alimsardjono, H., Takeshima, Y., Nakamura, H., Naritomi, K., Hirose, S., Onishi, S., Matsuo, M. <strong>Japanese cases of type 1 thanatophoric dysplasia exclusively carry a C to T transition at nucleotide 742 of the fibroblast growth factor receptor 3 gene.</strong> Biochem. Biophys. Res. Commun. 227: 236-239, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8858131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8858131</a>] [<a href="https://doi.org/10.1006/bbrc.1996.1495" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8858131">Pokharel et al. (1996)</a> described a Japanese type I TD patient followed for more than 9 years. They found that the patient had the arg248-to-cys mutation as did 4 other Japanese cases of type I TD. No association was found with the ser371-to-cys mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8858131" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The R248C mutation was the most frequent cause of thanatophoric dysplasia in the 91 cases reviewed in detail by <a href="#130" class="mim-tip-reference" title="Wilcox, W. R., Tavormina, P. L., Krakow, D., Kitoh, H., Lachman, R. S., Wasmuth, J. J., Thompson, L. M., Rimoin, D. L. <strong>Molecular, radiologic, and histopathologic correlations in thanatophoric dysplasia.</strong> Am. J. Med. Genet. 78: 274-281, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9677066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9677066</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19980707)78:3<274::aid-ajmg14>3.0.co;2-c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9677066">Wilcox et al. (1998)</a>, occurring in almost 50% (45) of the cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9677066" 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>Although prenatal diagnosis of TD had been accomplished by ultrasonography in the second trimester, it was not always possible to distinguish between TD and other osteochondrodysplasias in utero. Using restriction enzyme analysis, <a href="#103" class="mim-tip-reference" title="Sawai, H., Komori, S., Ida, A., Henmi, T., Bessho, T., Koyama, K. <strong>Prenatal diagnosis of thanatophoric dysplasia by mutational analysis of the fibroblast growth factor receptor 3 gene and a proposed correction of previously published PCR results.</strong> Prenatal Diag. 19: 21-24, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10073901/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10073901</a>] [<a href="https://doi.org/10.1002/(sici)1097-0223(199901)19:1<21::aid-pd457>3.0.co;2-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10073901">Sawai et al. (1999)</a> identified the common 742C-T mutation in the FGFR3 gene in a fetus at 27 weeks' gestation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10073901" 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="#43" class="mim-tip-reference" title="Hyland, V. J., Robertson, S. P., Flanagan, S., Savarirayan, R., Roscioli, T., Masel, J., Hayes, M., Glass, I. A. <strong>Somatic and germline mosaicism for a R248C missense mutation in FGFR3, resulting in a skeletal dysplasia distinct from thanatophoric dysplasia.</strong> Am. J. Med. Genet. 120A: 157-168, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12833394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12833394</a>] [<a href="https://doi.org/10.1002/ajmg.a.20012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12833394">Hyland et al. (2003)</a> described a woman who was a somatic and germline mosaic for the R248C missense mutation in FGFR3. She had disproportionate short stature, rhizomelic limb shortening, and other skeletal features accompanied by widespread acanthosis nigricans. These features were clearly different from those seen in thanatophoric dysplasia or other skeletal dysplasias. Her only pregnancy ended in delivery of a fetus with lethal short-limb dwarfism and pulmonary hyperplasia, strongly suggestive of thanatophoric dysplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12833394" 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>Nevus, Epidermal, Somatic</em></strong></p><p>
|
|
<a href="#35" class="mim-tip-reference" title="Hafner, C., van Oers, J. M. M., Vogt, T., Landthaler, M., Stoehr, R., Blaszyk, H., Hofstaedter, F., Zwarthoff, E. C., Hartmann, A. <strong>Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi.</strong> J. Clin. Invest. 116: 2201-2207, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16841094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16841094</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16841094[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/10.1172/JCI28163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16841094">Hafner et al. (2006)</a> analyzed the FGFR3 gene in 39 common epidermal nevi (<a href="/entry/162900">162900</a>) from 33 patients and identified the R248C mutation in 10 of 11 mutation-positive patients; In 4 patients tested, FGFR3 mutations were not found in adjacent, histologically normal skin. <a href="#35" class="mim-tip-reference" title="Hafner, C., van Oers, J. M. M., Vogt, T., Landthaler, M., Stoehr, R., Blaszyk, H., Hofstaedter, F., Zwarthoff, E. C., Hartmann, A. <strong>Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi.</strong> J. Clin. Invest. 116: 2201-2207, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16841094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16841094</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16841094[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/10.1172/JCI28163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16841094">Hafner et al. (2006)</a> concluded that a large proportion of epidermal nevi are caused by mosaicism of activating FGFR3 mutations in the human epidermis secondary to a postzygotic mutation in early embryonic development, and that the R248C mutation appears to be a hotspot for FGFR3 mutations in epidermal nevi. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16841094" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Garcia-Vargas, A., Hafner, C., Perez-Rodriguez, A. G., Rodriguez-Rojas, L. X., Gonzalez-Esqueda, P., Stoehr, R., Hernandez-Torres, M., Happle, R. <strong>An epidermal nevus syndrome with cerebral involvement caused by a mosaic FGFR3 mutation.</strong> Am. J. Med. Genet. 146A: 2275-2279, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18642369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18642369</a>] [<a href="https://doi.org/10.1002/ajmg.a.32429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18642369">Garcia-Vargas et al. (2008)</a> reported a 5-year-old Mexican girl with epidermal nevi, mental impairment, and seizures in whom they identified somatic mosaicism for a heterozygous R248C mutation in lesional skin and lymphocytes but not in normal skin. She had generalized linear epidermal nevi with a soft, velvety texture following the lines of Blaschko, and sparing the scalp, palms, and soles. She had delayed development, and brain CT showed cortical and subcortical atrophy, a subdural hygroma, and hypoplasia of the corpus callosum. The findings suggested that the mutation involved the skin, brain, and blood cells. Although there were no skeletal anomalies, <a href="#29" class="mim-tip-reference" title="Garcia-Vargas, A., Hafner, C., Perez-Rodriguez, A. G., Rodriguez-Rojas, L. X., Gonzalez-Esqueda, P., Stoehr, R., Hernandez-Torres, M., Happle, R. <strong>An epidermal nevus syndrome with cerebral involvement caused by a mosaic FGFR3 mutation.</strong> Am. J. Med. Genet. 146A: 2275-2279, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18642369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18642369</a>] [<a href="https://doi.org/10.1002/ajmg.a.32429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18642369">Garcia-Vargas et al. (2008)</a> considered the phenotype to be consistent with a mosaic manifestation of TD type I, but also proposed a preliminary designation of 'FGFR3 epidermal nevus syndrome.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18642369" 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>Multiple Myeloma, Somatic</em></strong></p><p>
|
|
<a href="#46" class="mim-tip-reference" title="Intini, D., Baldini, L., Fabris, S., Lombardi, L., Ciceri, G., Maiolo, A. T., Neri, A. <strong>Analysis of FGFR3 gene mutations in multiple myeloma patients with t(4;14).</strong> Brit. J. Haemat. 114: 362-364, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11529856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11529856</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2001.02957.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11529856">Intini et al. (2001)</a> investigated FGFR3 mutations in a series of 53 multiple myeloma (<a href="/entry/254500">254500</a>) cases, 11 of which had a t(4;14) translocation and FGFR3 overexpression. The arg248-to-cys mutation was found in 1 case with t(4;14). <a href="#46" class="mim-tip-reference" title="Intini, D., Baldini, L., Fabris, S., Lombardi, L., Ciceri, G., Maiolo, A. T., Neri, A. <strong>Analysis of FGFR3 gene mutations in multiple myeloma patients with t(4;14).</strong> Brit. J. Haemat. 114: 362-364, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11529856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11529856</a>] [<a href="https://doi.org/10.1046/j.1365-2141.2001.02957.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11529856">Intini et al. (2001)</a> concluded that FGFR3 mutations occur in only a small fraction of multiple myeloma cases with t(4;14). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11529856" 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>Keratosis, Seborrheic, Somatic</em></strong></p><p>
|
|
<a href="#63" class="mim-tip-reference" title="Logie, A., Dunois-Larde, C., Rosty, C., Levrel, O., Blanche, M., Ribeiro, A., Gasc, J.-M., Jorcano, J., Werner, S., Sastre-Garau, X., Thiery, J. P., Radvanyi, F. <strong>Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans.</strong> Hum. Molec. Genet. 14: 1153-1160, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15772091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15772091</a>] [<a href="https://doi.org/10.1093/hmg/ddi127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15772091">Logie et al. (2005)</a> identified a somatic R248C mutation in the FGFR3 gene in 5 seborrheic keratoses (<a href="/entry/182000">182000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15772091" 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 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, SER371CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121913484 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913484;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=rs121913484" 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=rs121913484" 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=RCV000017736 OR RCV000757295 OR RCV001528646" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017736, RCV000757295, RCV001528646" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017736...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 of 39 individuals with thanatophoric dysplasis type I (TD1; <a href="/entry/187600">187600</a>), <a href="#120" class="mim-tip-reference" title="Tavormina, P. L., Shiang, R., Thompson, L. M., Zhu, Y.-Z., Wilkin, D. J., Lachman, R. S., Wilcox, W. R., Rimoin, D. L., Cohn, D. H., Wasmuth, J. J. <strong>Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3.</strong> Nature Genet. 9: 321-328, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7773297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7773297</a>] [<a href="https://doi.org/10.1038/ng0395-321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7773297">Tavormina et al. (1995)</a> found an A-to-T transversion at nucleotide 1111 that caused a ser371-to-cys substitution in the extracellular region of the FGFR3 protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7773297" 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 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, TER807GLY
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121913101 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913101;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=rs121913101" 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=rs121913101" 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=RCV000017737 OR RCV000493112 OR RCV003155031" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017737, RCV000493112, RCV003155031" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017737...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By using a combination of single-strand conformation polymorphism (SSCP) and direct sequencing of amplified exons, <a href="#99" class="mim-tip-reference" title="Rousseau, F., Saugier, P., Le Merrer, M., Munnich, A., Delezoide, A.-L., Maroteaux, P., Bonaventure, J., Narcy, F., Sanak, M. <strong>Stop codon FGFR3 mutations in thanatophoric dwarfism type 1.</strong> Nature Genet. 10: 11-12, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7647778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7647778</a>] [<a href="https://doi.org/10.1038/ng0595-11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7647778">Rousseau et al. (1995)</a> found 3 different heterozygous base substitutions in the chain termination codon of FGFR3 in 5 of 15 patients with thanatophoric dysplasia type I (TD1; <a href="/entry/187600">187600</a>) without cloverleaf skull (codon 807, nucleotides 2458 and 2460). These mutations were expected to give rise to a protein elongated by 141 amino acids, as the mRNA continues to be translated through a 423-bp region until another in-frame stop codon is reached. This would result in a highly hydrophobic domain with an alpha-helix structure at the C-terminal end of the full-length protein. This was the first report of a stop codon mutation in an FGFR gene. Absence of stop codon mutations in the healthy parents and the finding of advanced paternal age at the time of conception gave support to the view that de novo mutations of paternal origin were involved. Of the 5 patients, 2 had a T-to-G transversion in the TGA stop codon, 2 had a T-to-A transversion in the TGA stop codon, and 1 had an A-to-T transversion in the TGA stop codon. The first of these mutations, TGA to GGA, represents ter807 to gly; the second, TGA to AGA, represents a ter807-to-arg change (<a href="#0008">134934.0008</a>); and the third, TGA to TGT, represents a ter807-to-cys change (<a href="#0009">134934.0009</a>). The classic example of a stop codon mutation is that found in the alpha-globin chain variant hemoglobin Constant Spring (<a href="/entry/141850#0001">141850.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7647778" 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 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, TER807ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121913101 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913101;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=rs121913101" 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=rs121913101" 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=RCV000017738 OR RCV000520562 OR RCV002504801" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017738, RCV000520562, RCV002504801" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017738...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 of 15 cases of thanatophoric dysplasia type I (TD1; <a href="/entry/187600">187600</a>) without cloverleaf skull, <a href="#99" class="mim-tip-reference" title="Rousseau, F., Saugier, P., Le Merrer, M., Munnich, A., Delezoide, A.-L., Maroteaux, P., Bonaventure, J., Narcy, F., Sanak, M. <strong>Stop codon FGFR3 mutations in thanatophoric dwarfism type 1.</strong> Nature Genet. 10: 11-12, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7647778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7647778</a>] [<a href="https://doi.org/10.1038/ng0595-11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7647778">Rousseau et al. (1995)</a> found a change in the termination codon, TGA to AGA (ter807 to arg), that resulted in a protein elongated by 141 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7647778" 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 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, TER807CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121913103 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913103;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=rs121913103" 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=rs121913103" 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=RCV000017739 OR RCV003155032 OR RCV004528117" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017739, RCV003155032, RCV004528117" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017739...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 of 15 patients with TD type I without cloverleaf skull, <a href="#99" class="mim-tip-reference" title="Rousseau, F., Saugier, P., Le Merrer, M., Munnich, A., Delezoide, A.-L., Maroteaux, P., Bonaventure, J., Narcy, F., Sanak, M. <strong>Stop codon FGFR3 mutations in thanatophoric dwarfism type 1.</strong> Nature Genet. 10: 11-12, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7647778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7647778</a>] [<a href="https://doi.org/10.1038/ng0595-11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7647778">Rousseau et al. (1995)</a> found a change in the chain termination codon, TGA to TGT (ter807 to cys), that resulted in a protein elongated by 141 amino acids. See also <a href="#0008">134934.0008</a> and <a href="#98" class="mim-tip-reference" title="Rousseau, F., El Ghouzzi, V., Delezoide, A. L., Legeai-Mallet, L., Le Merrer, M., Munnich, A., Bonaventure, J. <strong>Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1).</strong> Hum. Molec. Genet. 5: 509-512, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845844</a>] [<a href="https://doi.org/10.1093/hmg/5.4.509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845844">Rousseau et al. (1996)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7647778+8845844" 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 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, ASN540LYS, 1620C-A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28933068 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933068;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/rs28933068?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=rs28933068" 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=rs28933068" 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=RCV000017740 OR RCV000017771 OR RCV000255928 OR RCV000353403 OR RCV002273932 OR RCV004541008 OR RCV004786271" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017740, RCV000017771, RCV000255928, RCV000353403, RCV002273932, RCV004541008, RCV004786271" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017740...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 8 of 14 unrelated patients with hypochondroplasia (HCH; <a href="/entry/146000">146000</a>), <a href="#8" class="mim-tip-reference" title="Bellus, G. A., McIntosh, I., Smith, E. A., Aylsworth, A. S., Kaitila, I., Horton, W. A., Greenhaw, G. A., Hecht, J. T., Francomano, C. A. <strong>A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia.</strong> Nature Genet. 10: 357-359, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670477</a>] [<a href="https://doi.org/10.1038/ng0795-357" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670477">Bellus et al. (1995)</a> found a C-to-A transversion at nucleotide 1620 of the FGFR3 gene, resulting in an asn540-to-lys (N540K) substitution in the proximal tyrosine kinase domain of the protein. This mutation was demonstrated in the severely affected woman thought to represent a hypochondroplasia/achondroplasia compound heterozygote (<a href="#68" class="mim-tip-reference" title="McKusick, V. A., Kelly, T. E., Dorst, J. P. <strong>Observations suggesting allelism of the achondroplasia and hypochondroplasia genes.</strong> J. Med. Genet. 10: 11-16, 1973.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4697848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4697848</a>] [<a href="https://doi.org/10.1136/jmg.10.1.11" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4697848">McKusick et al., 1973</a>); the other allele carried the common achondroplasia mutation: gly380 to arg (<a href="#0001">134934.0001</a>). <a href="#87" class="mim-tip-reference" title="Prinos, P., Costa, T., Sommer, A., Kilpatrick, M. W., Tsipouras, P. <strong>A common FGFR3 gene mutation in hypochondroplasia.</strong> Hum. Molec. Genet. 4: 2097-2101, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589686/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589686</a>] [<a href="https://doi.org/10.1093/hmg/4.11.2097" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8589686">Prinos et al. (1995)</a> found the same mutation in 4 cases and confirmed its occurrence in the hypochondroplasia/achondroplasia compound heterozygote. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8589686+7670477+4697848" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Bellus, G. A., McIntosh, I., Smith, E. A., Aylsworth, A. S., Kaitila, I., Horton, W. A., Greenhaw, G. A., Hecht, J. T., Francomano, C. A. <strong>A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia.</strong> Nature Genet. 10: 357-359, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670477</a>] [<a href="https://doi.org/10.1038/ng0795-357" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670477">Bellus et al. (1995)</a> referred to the nucleotide as 1620; <a href="#87" class="mim-tip-reference" title="Prinos, P., Costa, T., Sommer, A., Kilpatrick, M. W., Tsipouras, P. <strong>A common FGFR3 gene mutation in hypochondroplasia.</strong> Hum. Molec. Genet. 4: 2097-2101, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589686/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589686</a>] [<a href="https://doi.org/10.1093/hmg/4.11.2097" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8589686">Prinos et al. (1995)</a> referred to the nucleotide as 1659. Both groups numbered the amino acid as 540. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8589686+7670477" 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="#42" class="mim-tip-reference" title="Huggins, M. J., Smith, J. R., Chun, K., Ray, P. N., Shah, J. K., Whelan, D. T. <strong>Achondroplasia-hypochondroplasia complex in a newborn infant.</strong> Am. J. Med. Genet. 84: 396-400, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10360392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10360392</a>]" pmid="10360392">Huggins et al. (1999)</a> reported an 8-month-old girl with achondroplasia/hypochondroplasia whose father had the G380R mutation and whose mother had the N450K mutation. <a href="#17" class="mim-tip-reference" title="Chitayat, D., Fernandez, B., Gardner, A., Moore, L., Glance, P., Dunn, M., Chun, K., Sgro, M., Ray, P., Allingham-Hawkins, D. <strong>Compound heterozygosity for the achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome.</strong> Am. J. Med. Genet. 84: 401-405, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10360393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10360393</a>]" pmid="10360393">Chitayat et al. (1999)</a> simultaneously reported an infant boy with achondroplasia/hypochondroplasia whose mother had the G380R mutation and whose father had the N450K mutation. Molecular analysis confirmed the compound heterozygosity of both children, who displayed an intermediate phenotype that was more severe than either condition in the heterozygous state but less severe than homozygous ACH. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10360393+10360392" 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="#88" class="mim-tip-reference" title="Prinster, C., Carrera, P., Del Maschio, M., Weber, G., Maghnie, M., Vigone, M. C., Mora, S., Tonini, G., Rigon, F., Beluffi, G., Severi, F., Chiumello, G., Ferrari, M. <strong>Comparison of clinical-radiological and molecular findings in hypochondroplasia.</strong> Am. J. Med. Genet. 75: 109-112, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9450868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9450868</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19980106)75:1<109::aid-ajmg22>3.0.co;2-p" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9450868">Prinster et al. (1998)</a> selected 18 patients with a phenotype compatible with hypochondroplasia based on the most common radiologic criteria. The presence of the N540K mutation was verified by restriction enzyme digestions in 9 of the 18 patients. Although similar in phenotype to patients without the mutation, these 9 had the additional feature of relative macrocephaly. Furthermore, the association of the unchanged or narrow interpedicular distance with the fibula longer than the tibia was more common in patients with the N540K mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9450868" 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>Among 65 patients with hypochondroplasia, <a href="#89" class="mim-tip-reference" title="Ramaswami, U., Rumsby, G., Hindmarsh, P. C., Brook, C. G. D. <strong>Genotype and phenotype in hypochondroplasia.</strong> J. Pediat. 133: 99-102, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9672519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9672519</a>] [<a href="https://doi.org/10.1016/s0022-3476(98)70186-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9672519">Ramaswami et al. (1998)</a> found that 28 (43%) were heterozygous for the 1620C-A transversion resulting in the asn540-to-lys amino acid substitution in the tyrosine kinase domain of FGFR3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9672519" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Angle, B., Hersh, J. H., Christensen, K. M. <strong>Molecularly proven hypochondroplasia with cloverleaf skull deformity: a novel association.</strong> Clin. Genet. 54: 417-420, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9842995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9842995</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1998.tb03756.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9842995">Angle et al. (1998)</a> found the 1620C-A mutation in FGFR3 in a patient with hypochondroplasia associated with cloverleaf skull deformity. Cloverleaf skull had not previously been reported in hypochondroplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9842995" 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 CROUZON SYNDROME WITH ACANTHOSIS NIGRICANS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, ALA391GLU
|
|
</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> rs28931615 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28931615;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/rs28931615?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=rs28931615" 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=rs28931615" 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=RCV000017726 OR RCV000194803 OR RCV000414319 OR RCV000623005" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017726, RCV000194803, RCV000414319, RCV000623005" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017726...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 patients with Crouzon syndrome with acanthosis nigricans (<a href="/entry/612247">612247</a>), including a mother and daughter and 2 patients with sporadic disease, <a href="#69" class="mim-tip-reference" title="Meyers, G. A., Orlow, S. J., Munro, I. R., Przylepa, K. A., Jabs, E. W. <strong>Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans.</strong> Nature Genet. 11: 462-464, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7493034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7493034</a>] [<a href="https://doi.org/10.1038/ng1295-462" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7493034">Meyers et al. (1995)</a> identified the same heterozygous 1172C-A transversion in the FGFR3 gene, resulting in an ala391-to-glu (A391E) substitution in the transmembrane domain. The A391E mutation was not present in 16 unrelated Crouzon syndrome patients with FGFR2 mutations, 13 unrelated Crouzon syndrome patients without FGFR2 IgIII domain mutations, or 50 unrelated controls. In addition, the authors found no FGFR3 mutations in 2 unrelated patients with isolated acanthosis nigricans (<a href="/entry/100600">100600</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7493034" 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="#3" class="mim-tip-reference" title="Arnaud-Lopez, L., Fragoso, R., Mantilla-Capacho, J., Barros-Nunez, P. <strong>Crouzon with acanthosis nigricans: further delineation of the syndrome.</strong> Clin. Genet. 72: 405-410, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17935505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17935505</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00884.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17935505">Arnaud-Lopez et al. (2007)</a> reported 2 additional unrelated girls with Crouzon syndrome with acanthosis nigricans associated with a heterozygous A391E mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17935505" 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 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, ASN540LYS, 1620C-G
|
|
</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> rs28933068 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933068;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/rs28933068?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=rs28933068" 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=rs28933068" 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=RCV000017741 OR RCV000255372 OR RCV000415460 OR RCV000622950 OR RCV000763122 OR RCV001332222 OR RCV001804740 OR RCV002276553 OR RCV004737156" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017741, RCV000255372, RCV000415460, RCV000622950, RCV000763122, RCV001332222, RCV001804740, RCV002276553, RCV004737156" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017741...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with hypochondroplasia (HCH; <a href="/entry/146000">146000</a>), <a href="#87" class="mim-tip-reference" title="Prinos, P., Costa, T., Sommer, A., Kilpatrick, M. W., Tsipouras, P. <strong>A common FGFR3 gene mutation in hypochondroplasia.</strong> Hum. Molec. Genet. 4: 2097-2101, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589686/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589686</a>] [<a href="https://doi.org/10.1093/hmg/4.11.2097" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8589686">Prinos et al. (1995)</a> found a C-to-G transversion at nucleotide 1659 (nucleotide 1620 in the numbering system of <a href="#8" class="mim-tip-reference" title="Bellus, G. A., McIntosh, I., Smith, E. A., Aylsworth, A. S., Kaitila, I., Horton, W. A., Greenhaw, G. A., Hecht, J. T., Francomano, C. A. <strong>A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia.</strong> Nature Genet. 10: 357-359, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670477</a>] [<a href="https://doi.org/10.1038/ng0795-357" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7670477">Bellus et al. (1995)</a>) of the FGFR3 gene, predicted to cause an asn540-to-lys (N540K) substitution. The N540K mutation causing hypochondroplasia and known to be caused by either of 2 substitutions in the same nucleotide (1620C-G and 1620C-A; <a href="#0010">134934.0010</a>) is comparable to the gly380-to-arg mutation which causes achondroplasia and can be due to either of 2 different mutations in the same nucleotide (see <a href="#0001">134934.0001</a> and <a href="#0002">134934.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8589686+7670477" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of 18 Taiwanese patients with hypochondroplasia, <a href="#125" class="mim-tip-reference" title="Tsai, F.-J., Wu, J.-Y., Tsai, C.-H., Chang, J.-G. <strong>Identification of a common N540K mutation in 8/18 Taiwanese hypochondroplasia patients: further evidence for genetic heterogeneity. (Letter)</strong> Clin. Genet. 55: 279-280, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10361991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10361991</a>] [<a href="https://doi.org/10.1034/j.1399-0004.1999.550412.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10361991">Tsai et al. (1999)</a> identified a C-to-A transversion at nucleotide 1659 (in their numbering system) of the FGFR3 gene in 6 patients, and a C-to-G transversion of the same nucleotide in 4 patients. The molecular basis in the remaining 8 patients was unknown. (There was discrepancy between the text of the paper and the title; the latter stated that 8 of 18 had the N540K mutation.) <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10361991" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#25" class="mim-tip-reference" title="Fofanova, O. V., Takamura, N., Kinoshita, E., Meerson, E. M., Iljina, V. K., Nechvolodova, O. L., Evgrafov, O. V., Peterkova, V. A., Yamashita, S. <strong>A missense mutation of C1659 in the fibroblast growth factor receptor 3 gene in Russian patients with hypochondroplasia.</strong> Endocr. J. 45: 791-795, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10395236/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10395236</a>] [<a href="https://doi.org/10.1507/endocrj.45.791" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10395236">Fofanova et al. (1998)</a> studied 16 patients with hypochondroplasia, 12 familial and 4 sporadic. In 9 patients (56.3%), the heterozygous N540K mutation was detected; in 6 patients the mutation was due to 1659C-A and in 3 patients to 1659C-G. The ratios of familial and sporadic cases among patients who carried FGFR3 mutations were similar. The 7 patients who lacked the N540K mutation were all familial. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10395236" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0013" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
CERVICAL CANCER, SOMATIC, INCLUDED<br />
|
|
BLADDER CANCER, SOMATIC, INCLUDED<br />
|
|
KERATOSIS, SEBORRHEIC, SOMATIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, SER249CYS
|
|
</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> rs121913483 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913483;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/rs121913483?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=rs121913483" 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=rs121913483" 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=RCV000017742 OR RCV000017743 OR RCV000017744 OR RCV000017745 OR RCV000297175 OR RCV000420501 OR RCV000763119 OR RCV002276554 OR RCV003155033 OR RCV003758684 OR RCV003989294 OR RCV004532377 OR RCV004795921" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017742, RCV000017743, RCV000017744, RCV000017745, RCV000297175, RCV000420501, RCV000763119, RCV002276554, RCV003155033, RCV003758684, RCV003989294, RCV004532377, RCV004795921" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017742...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#119" class="mim-tip-reference" title="Tavormina, P. L., Rimoin, D. L., Cohn, D. H., Zhu, Y.-Z., Shiang, R., Wasmuth, J. J. <strong>Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type I.</strong> Hum. Molec. Genet. 4: 2175-2177, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589699</a>] [<a href="https://doi.org/10.1093/hmg/4.11.2175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8589699">Tavormina et al. (1995)</a> described another cysteine-generating mutation in the extracellular domain of FGFR3: a C-to-G transversion at nucleotide 746, which changed ser249 to cys. The authors speculated that the unpaired cysteine residue in this region of the protein might result in formation of intermolecular disulfide bonds between 2 mutant FGFR3 monomers and thereby constitutively activate the receptor complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8589699" 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>Of the FGFR3 mutations identified by <a href="#13" class="mim-tip-reference" title="Cappellen, D., De Oliveira, C., Ricol, D., Gil Diez de Medina, S., Bourdin, J., Sastre-Garau, X., Chopin, D., Thiery, J. P., Radvanyi, F. <strong>Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. (Letter)</strong> Nature Genet. 23: 18-20, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10471491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10471491</a>] [<a href="https://doi.org/10.1038/12615" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10471491">Cappellen et al. (1999)</a> in epithelial tumors, the ser249-to-cys somatic mutation was the most common, affecting 5 of 9 bladder cancers (<a href="/entry/109800">109800</a>) and 3 of 3 cervical cancers (<a href="/entry/603956">603956</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10471491" 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="#63" class="mim-tip-reference" title="Logie, A., Dunois-Larde, C., Rosty, C., Levrel, O., Blanche, M., Ribeiro, A., Gasc, J.-M., Jorcano, J., Werner, S., Sastre-Garau, X., Thiery, J. P., Radvanyi, F. <strong>Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans.</strong> Hum. Molec. Genet. 14: 1153-1160, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15772091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15772091</a>] [<a href="https://doi.org/10.1093/hmg/ddi127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15772091">Logie et al. (2005)</a> identified a somatic S249C mutation in the FGFR3 gene in 5 seborrheic keratoses (<a href="/entry/182000">182000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15772091" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0014" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MUENKE SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
SAETHRE-CHOTZEN SYNDROME, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, PRO250ARG
|
|
</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> rs4647924 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs4647924;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/rs4647924?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=rs4647924" 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=rs4647924" 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=RCV000017746 OR RCV000017747 OR RCV000121075 OR RCV000193831 OR RCV000436385 OR RCV000622712 OR RCV000626772 OR RCV000987393 OR RCV001334261 OR RCV001813993 OR RCV002273933 OR RCV003483434 OR RCV004554603 OR RCV005003375" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017746, RCV000017747, RCV000121075, RCV000193831, RCV000436385, RCV000622712, RCV000626772, RCV000987393, RCV001334261, RCV001813993, RCV002273933, RCV003483434, RCV004554603, RCV005003375" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017746...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#6" class="mim-tip-reference" title="Bellus, G. A., Gaudenz, K., Zackai, E. H., Clarke, L. A., Szabo, J., Francomano, C. A., Muenke, M. <strong>Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes.</strong> Nature Genet. 14: 174-176, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8841188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8841188</a>] [<a href="https://doi.org/10.1038/ng1096-174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8841188">Bellus et al. (1996)</a> described a pro250-to-arg (P250R) amino acid substitution in FGFR3 (caused by a C-to-G transversion at position 749 of the coding cDNA sequence) in 10 unrelated patients with nonsyndromic autosomal dominant or sporadic craniosynostosis. This mutation is in the extracellular domain of the FGFR3 protein and occurs precisely at the position within the FGFR3 protein analogous to that of mutations in FGFR1 (P252R; <a href="/entry/136350#0001">136350.0001</a>) and FGFR2 (P253R; <a href="/entry/176943#0011">176943.0011</a>), previously reported in Pfeiffer (<a href="/entry/101600">101600</a>) and Apert syndromes, respectively. They pictured the craniofacial and extremity anomalies in some of these cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8841188" 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="#74" class="mim-tip-reference" title="Muenke, M., Gripp, K. W., McDonald-McGinn, D. M., Gaudenz, K., Whitaker, L. A., Bartlett, S. P., Markowitz, R. I., Robin, N. H., Nwokoro, N., Mulvihill, J. J., Losken, W., Mulliken, J. B., Guttmacher, A. E., Wilroy, R. S., Clarke, L. A., Hollway, G., Ades, L. C., Haan, E. A., Mulley, J. C., Cohen, M. M., Jr., Bellus, G. A., Francomano, C. A., Moloney, D. M., Wall, S. A., Wilkie, A. O. M., Zackai, E. H. <strong>A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome.</strong> Am. J. Hum. Genet. 60: 555-564, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042914</a>]" pmid="9042914">Muenke et al. (1997)</a> provided extensive information on a series of 61 individuals from 20 unrelated families in which coronal craniosynostosis is due to this mutation, defining a new clinical syndrome that is referred to as Muenke nonsyndromic coronal craniosynostosis (<a href="/entry/602849">602849</a>). At about the same time, <a href="#71" class="mim-tip-reference" title="Moloney, D. M., Wall, S. A., Ashworth, G. J., Oldridge, M., Glass, I. A., Francomano, C. A., Muenke, M., Wilkie, A. O. M. <strong>Prevalence of pro250arg mutation of fibroblast growth factor receptor 3 in coronal craniosynostosis.</strong> Lancet 349: 1059-1062, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9107244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9107244</a>] [<a href="https://doi.org/10.1016/s0140-6736(96)09082-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9107244">Moloney et al. (1997)</a> studied 26 patients with coronal craniosynostosis but no syndromic diagnosis to determine the frequency of the 749C-G (pro250-to-arg) mutation in FGFR3. Heterozygosity for the mutation was found in 8 (31%) of the 26 probands. In 2 cases, the mutation showed autosomal dominant transmission with evidence of variable expressivity; the remaining 6 cases were sporadic. <a href="#71" class="mim-tip-reference" title="Moloney, D. M., Wall, S. A., Ashworth, G. J., Oldridge, M., Glass, I. A., Francomano, C. A., Muenke, M., Wilkie, A. O. M. <strong>Prevalence of pro250arg mutation of fibroblast growth factor receptor 3 in coronal craniosynostosis.</strong> Lancet 349: 1059-1062, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9107244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9107244</a>] [<a href="https://doi.org/10.1016/s0140-6736(96)09082-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9107244">Moloney et al. (1997)</a> pointed out that the 749C nucleotide has one of the highest mutation rates described in the human genome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9042914+9107244" 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="#92" class="mim-tip-reference" title="Reardon, W., Wilkes, D., Rutland, P., Pulleyn, L. J., Malcolm, S., Dean, J. C. S., Evans, R. D., Jones, B. M., Hayward, R., Hall, C. M., Nevin, N. C., Baraitser, M., Winter, R. M. <strong>Craniosynostosis associated with FGFR3 pro250-to-arg mutation results in a range of clinical presentations including unisutural sporadic craniosynostosis.</strong> J. Med. Genet. 34: 632-636, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9279753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9279753</a>] [<a href="https://doi.org/10.1136/jmg.34.8.632" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9279753">Reardon et al. (1997)</a> reported 9 individuals with the P250R mutation. The authors documented a variable clinical presentation and contrasted this with the phenotype produced by the analogous mutation in FGFR1 (P252R; <a href="/entry/136350#0001">136350.0001</a>) and FGFR2 (P253R; <a href="/entry/176943#0011">176943.0011</a>). In particular, <a href="#92" class="mim-tip-reference" title="Reardon, W., Wilkes, D., Rutland, P., Pulleyn, L. J., Malcolm, S., Dean, J. C. S., Evans, R. D., Jones, B. M., Hayward, R., Hall, C. M., Nevin, N. C., Baraitser, M., Winter, R. M. <strong>Craniosynostosis associated with FGFR3 pro250-to-arg mutation results in a range of clinical presentations including unisutural sporadic craniosynostosis.</strong> J. Med. Genet. 34: 632-636, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9279753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9279753</a>] [<a href="https://doi.org/10.1136/jmg.34.8.632" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9279753">Reardon et al. (1997)</a> noted mental retardation in 4 of the 9 cases, which they reported was unrelated to the management of the craniosynostosis. <a href="#92" class="mim-tip-reference" title="Reardon, W., Wilkes, D., Rutland, P., Pulleyn, L. J., Malcolm, S., Dean, J. C. S., Evans, R. D., Jones, B. M., Hayward, R., Hall, C. M., Nevin, N. C., Baraitser, M., Winter, R. M. <strong>Craniosynostosis associated with FGFR3 pro250-to-arg mutation results in a range of clinical presentations including unisutural sporadic craniosynostosis.</strong> J. Med. Genet. 34: 632-636, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9279753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9279753</a>] [<a href="https://doi.org/10.1136/jmg.34.8.632" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9279753">Reardon et al. (1997)</a> suggested that there was a significant overlap between Saethre-Chotzen syndrome (<a href="/entry/101400">101400</a>), a common autosomal dominant condition of craniosynostosis and limb anomalies, and the phenotype produced by this mutation. They also noted unisutural craniosynostosis in 3 of the 9 cases to emphasize the caution with which the recurrence risks should be approached in craniosynostosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9279753" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of 32 unrelated patients with features of Saethre-Chotzen syndrome, <a href="#84" class="mim-tip-reference" title="Paznekas, W. A., Cunningham, M. L., Howard, T. D., Korf, B. R., Lipson, M. H., Grix, A. W., Feingold, M., Goldberg, R., Borochowitz, Z., Aleck, K., Mulliken, J., Yin, M., Jabs, E. W. <strong>Genetic heterogeneity of Saethre-Chotzen syndrome, due to TWIST and FGFR mutations.</strong> Am. J. Hum. Genet. 62: 1370-1380, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9585583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9585583</a>] [<a href="https://doi.org/10.1086/301855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9585583">Paznekas et al. (1998)</a> identified 7 families with the P250R mutation of the FGFR3 gene. The overlap in clinical features and the presence, in the same genes, of mutations for more than one craniosynostotic condition, such as Saethre-Chotzen, Crouzon, and Pfeiffer syndromes, suggested that the TWIST1 gene (<a href="/entry/601622">601622</a>), which is most frequently the site of mutations causing Saethre-Chotzen syndrome, and FGFRs are components of the same molecular pathway involved in the modulation of craniofacial and limb development in humans. The clinical features of the patients who were referred with the possible diagnosis of Saethre-Chotzen syndrome and who were found to have the FGFR3 mutation were not obviously different from those of individuals with the TWIST1 mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9585583" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Golla, A., Lichmer, P., von Gernet, S., Winterpacht, A., Fairley, J., Murken, J., Schuffenhauer, S. <strong>Phenotypic expression of the fibroblast growth factor receptor 3 (FGFR3) mutation P250R in a large craniosynostosis family.</strong> J. Med. Genet. 34: 683-684, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9279764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9279764</a>] [<a href="https://doi.org/10.1136/jmg.34.8.683" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9279764">Golla et al. (1997)</a> described a large German family with the P250R mutation in which there was also considerable phenotypic variability among individuals with the identical mutation. The clinical features in this family had been described by <a href="#128" class="mim-tip-reference" title="von Gernet, S., Schuffenhauer, S., Golla, A., Lichtner, P., Balg, S., Muhlbauer, W., Murken, J., Fairley, J., Meitinger, T. <strong>Craniosynostosis suggestive of Saethre-Chotzen syndrome: clinical description of a large kindred and exclusion of candidate regions on 7p.</strong> Am. J. Med. Genet. 63: 177-184, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8723106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8723106</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960503)63:1<177::AID-AJMG31>3.0.CO;2-J" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8723106">von Gernet et al. (1996)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9279764+8723106" 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="#34" class="mim-tip-reference" title="Gripp, K. W., McDonald-McGinn, D. M., Gaudenz, K., Whitaker, L. A., Bartlett, S. P., Glat, P. M., Cassileth, L. B., Mayro, R., Zackai, E. H., Muenke, M. <strong>Identification of a genetic cause for isolated unilateral coronal synostosis: a unique mutation in the fibroblast growth factor receptor 3.</strong> J. Pediat. 132: 714-716, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9580776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9580776</a>] [<a href="https://doi.org/10.1016/s0022-3476(98)70366-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9580776">Gripp et al. (1998)</a> found the P250R mutation in 4 of 37 patients with synostotic anterior plagiocephaly (literally 'oblique head'). In 3 mutation-positive patients with full parental studies, a parent with an extremely mild phenotype was found to carry the same mutation. None of the 6 patients with nonsynostotic plagiocephaly and none of the 4 patients with additional suture synostosis had the FGFR3 mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9580776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#41" class="mim-tip-reference" title="Hollway, G. E., Suthers, G. K., Battese, K. M., Turner, A. M., David, D. J., Mulley, J. C. <strong>Deafness due to pro250-to-arg mutation of FGFR3. (Letter)</strong> Lancet 351: 877-878, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9525367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9525367</a>] [<a href="https://doi.org/10.1016/S0140-6736(98)24012-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9525367">Hollway et al. (1998)</a> found the P250R mutation in FGFR3 in an extensive family with craniosynostosis and deafness, extending through 5 generations. The deafness was congenital, bilateral, sensorineural, and of moderate degree. Four family members had craniosynostosis evident at clinical review; 2 required surgery, and 1 was symptomatically deaf. Thirteen other affected members of the family had no evidence of craniosynostosis but were either symptomatically deaf or required bilateral hearing aids. <a href="#41" class="mim-tip-reference" title="Hollway, G. E., Suthers, G. K., Battese, K. M., Turner, A. M., David, D. J., Mulley, J. C. <strong>Deafness due to pro250-to-arg mutation of FGFR3. (Letter)</strong> Lancet 351: 877-878, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9525367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9525367</a>] [<a href="https://doi.org/10.1016/S0140-6736(98)24012-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9525367">Hollway et al. (1998)</a> thought that the craniosynostosis and deafness were not coincidentally associated and that the low penetrance of symptomatic craniosynostosis in this family raised the possibility that some families with the P250R mutation may present with deafness only. They pointed out that 1 locus for autosomal dominant nonsyndromal deafness (DFNA6; <a href="/entry/600965">600965</a>) maps to 4p16.3, the location of the FGFR3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9525367" 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="#94" class="mim-tip-reference" title="Robin, N. H., Scott, J. A., Cohen, A. R., Goldstein, J. A. <strong>Nonpenetrance in FGFR3-associated coronal synostosis syndrome. (Letter)</strong> Am. J. Med. Genet. 80: 296-297, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9843059/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9843059</a>]" pmid="9843059">Robin et al. (1998)</a> described a woman who was completely clinically and radiologically normal but was carrying the P250R mutation. <a href="#32" class="mim-tip-reference" title="Graham, J. M., Jr., Braddock, S. R., Mortier, G. R., Lachman, R., Van Dop, C., Jabs, E. W. <strong>Syndrome of coronal craniosynostosis with brachydactyly and carpal tarsal coalition due to Pro250Arg mutation in FGFR3 gene.</strong> Am. J. Med. Genet. 77: 322-329, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9600744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9600744</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19980526)77:4<322::aid-ajmg14>3.0.co;2-k" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9600744">Graham et al. (1998)</a> suggested that carpal-tarsal fusion may be the most specific finding for the FGFR3 mutation, being present in some individuals who did not have craniosynostosis. The patient reported by <a href="#94" class="mim-tip-reference" title="Robin, N. H., Scott, J. A., Cohen, A. R., Goldstein, J. A. <strong>Nonpenetrance in FGFR3-associated coronal synostosis syndrome. (Letter)</strong> Am. J. Med. Genet. 80: 296-297, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9843059/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9843059</a>]" pmid="9843059">Robin et al. (1998)</a> did not have carpal-tarsal fusion. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9600744+9843059" 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="#56" class="mim-tip-reference" title="Lajeunie, E., El Ghouzzi, V., Le Merrer, M., Munnich, A., Bonaventure, J., Renier, D. <strong>Sex related expressivity of the phenotype in coronal craniosynostosis caused by the recurrent P250R FGFR3 mutation.</strong> J. Med. Genet. 36: 9-13, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9950359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9950359</a>]" pmid="9950359">Lajeunie et al. (1999)</a> studied 62 patients with sporadic or familial forms of coronal craniosynostosis. The P250R mutation was identified in 20 probands from 27 unrelated families (74%), while only 6 of 35 sporadic cases (17%) were found to have this mutation. In both familial and sporadic cases, females were more severely affected, with 68% of females but only 35% of males having brachycephaly. In the most severely affected individuals, bicoronal craniosynostosis was associated with hypertelorism and marked bulging of the temporal fossae, features that <a href="#56" class="mim-tip-reference" title="Lajeunie, E., El Ghouzzi, V., Le Merrer, M., Munnich, A., Bonaventure, J., Renier, D. <strong>Sex related expressivity of the phenotype in coronal craniosynostosis caused by the recurrent P250R FGFR3 mutation.</strong> J. Med. Genet. 36: 9-13, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9950359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9950359</a>]" pmid="9950359">Lajeunie et al. (1999)</a> concluded might be helpful for clinical diagnosis. <a href="#56" class="mim-tip-reference" title="Lajeunie, E., El Ghouzzi, V., Le Merrer, M., Munnich, A., Bonaventure, J., Renier, D. <strong>Sex related expressivity of the phenotype in coronal craniosynostosis caused by the recurrent P250R FGFR3 mutation.</strong> J. Med. Genet. 36: 9-13, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9950359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9950359</a>]" pmid="9950359">Lajeunie et al. (1999)</a> concluded that the P250R mutation is most often familial and is associated with a more severe phenotype in females than in males. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9950359" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="El Ghouzzi, V., Lajeunie, E., Le Merrer, M., Cormier-Daire, V., Renier, D., Munnich, A., Bonaventure, J. <strong>Mutations within or upstream of the basic helix-loop-helix domain of the TWIST gene are specific to Saethre-Chotzen syndrome.</strong> Europ. J. Hum. Genet. 7: 27-33, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10094188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10094188</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200240" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10094188">El Ghouzzi et al. (1999)</a> found the P250R mutation in 2 of 22 cases of Saethre-Chotzen syndrome. The largest number of cases (16/22) were found to have mutations in the TWIST1 gene. In 4 of the 22 cases, no mutations were found in either TWIST1 or FGFR3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10094188" 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="#96" class="mim-tip-reference" title="Roscioli, T., Flanagan, S., Mortimore, R. J., Kumar, P., Weedon, D., Masel, J., Lewandowski, R., Hyland, V., Glass, I. A. <strong>Premature calvarial synostosis and epidermal hyperplasia (Beare-Stevenson syndrome-like anomalies) resulting from a P250R missense mutation in the gene encoding fibroblast growth factor receptor 3.</strong> Am. J. Med. Genet. 101: 187-194, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11424131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11424131</a>] [<a href="https://doi.org/10.1002/ajmg.1369" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11424131">Roscioli et al. (2001)</a> described a patient with severe premature calvarial synostosis and epidermal hyperplasia. Although the phenotype was consistent with that of a mild presentation of Beare-Stevenson syndrome (<a href="/entry/123790">123790</a>), molecular analysis of FGFR2 (<a href="/entry/176943">176943</a>) revealed wildtype sequence only. Molecular analysis of FGFR3 identified a heterozygous P250R missense mutation in both the proposita and her mildly affected father. The cutis gyrata in the daughter was located on the left palm, accompanied by deep skin creasing of both soles. In addition, a clearly demarcated darkened linear streak (initially macular) was present on the left forearm. At the age of 18 months, normal skin overlaid the neck and flexural regions. The father showed macrocephaly with some excessive creasing/thickening of the forehead skin and hypertelorism, but the skull was otherwise normal with no evidence of past premature craniosynostosis. This case extended the clinical spectrum of the P250R mutation to encompass epidermal hyperplasia and documented the phenomenon of activated FGFR receptors stimulating common downstream developmental pathways, resulting in overlapping clinical outcomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11424131" 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="#64" class="mim-tip-reference" title="Lowry, R. B., Jabs, E. W., Graham, G. E., Gerritsen, J., Fleming, J. <strong>Syndrome of coronal craniosynostosis, Klippel-Feil anomaly, and Sprengel shoulder with and without pro250arg mutation in the FGFR3 gene.</strong> Am. J. Med. Genet. 104: 112-119, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11746040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11746040</a>] [<a href="https://doi.org/10.1002/ajmg.10049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11746040">Lowry et al. (2001)</a> reported a family in which members with coronal craniosynostosis, skeletal abnormalities of the hands, and sensorineural hearing loss had the P250R mutation. One family member also had a Sprengel shoulder anomaly (<a href="/entry/184400">184400</a>) and multiple cervical spine anomalies consistent with Klippel-Feil anomaly (<a href="/entry/118100">118100</a>). The authors reported an additional case with an identical phenotype without the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11746040" 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="#90" class="mim-tip-reference" title="Rannan-Eliya, S. V., Taylor, I. B., de Heer, I. M., van den Ouweland, A. M. W., Wall, S. A., Wilkie, A. O. M. <strong>Paternal origin of FGFR3 mutations in Muenke-type craniosynostosis.</strong> Hum. Genet. 115: 200-207, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15241680/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15241680</a>] [<a href="https://doi.org/10.1007/s00439-004-1151-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15241680">Rannan-Eliya et al. (2004)</a> studied 19 cases of Muenke syndrome due to de novo P250R mutations in FGFR3. All 10 informative cases were of paternal origin; the average paternal age at birth for all 19 cases was 34.7 years. The authors noted that exclusive paternal origin and increased paternal age had previously been described for the G380R mutation in FGFR3 (<a href="#0001">134934.0001</a>) and mutations in FGFR2 (e.g., S252W, <a href="/entry/176943#0010">176943.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15241680" 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 surface plasmon resonance analysis and x-ray crystallography, <a href="#44" class="mim-tip-reference" title="Ibrahimi, O. A., Zhang, F., Eliseenkova, A. V., Linhardt, R. J., Mohammadi, M. <strong>Proline to arginine mutations in FGF receptors 1 and 3 result in Pfeiffer and Muenke craniosynostosis syndromes through enhancement of FGF binding affinity.</strong> Hum. Molec. Genet. 13: 69-78, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14613973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14613973</a>] [<a href="https://doi.org/10.1093/hmg/ddh011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14613973">Ibrahimi et al. (2004)</a> characterized the effects of proline-to-arginine mutations in FGFR1c and FGFR3c on ligand binding. Both the FGFR1c P252R and FGFR3c P250R mutations exhibited an enhancement in ligand binding in comparison to their respective wildtype receptors. Binding of both mutant receptors to FGF9 (<a href="/entry/600921">600921</a>) was notably enhanced and implicated FGF9 as a potential pathophysiologic ligand for mutant FGFRs in mediating craniosynostosis. The crystal structure of P252R mutant in complex with FGF2 (<a href="/entry/134920">134920</a>) demonstrated that enhanced ligand binding was due to an additional set of receptor-ligand hydrogen bonds, similar to those gain-of-function interactions that occur in the crystal structure of FGFR2c P253R (<a href="/entry/176943#0011">176943.0011</a>) mutant in complex with FGF2. However, unlike the P253R mutant, neither the FGFR1c P250R mutant nor the FGFR3c P250R mutant bound appreciably to FGF7 (<a href="/entry/148180">148180</a>) or FGF10 (<a href="/entry/602115">602115</a>). <a href="#44" class="mim-tip-reference" title="Ibrahimi, O. A., Zhang, F., Eliseenkova, A. V., Linhardt, R. J., Mohammadi, M. <strong>Proline to arginine mutations in FGF receptors 1 and 3 result in Pfeiffer and Muenke craniosynostosis syndromes through enhancement of FGF binding affinity.</strong> Hum. Molec. Genet. 13: 69-78, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14613973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14613973</a>] [<a href="https://doi.org/10.1093/hmg/ddh011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14613973">Ibrahimi et al. (2004)</a> suggested that this might explain why limb phenotypes observed in type I Pfeiffer syndrome and Muenke syndrome are less severe than limb abnormalities observed in Apert syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14613973" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Almeida, M. R., Campos-Xavier, A. B., Medeira, A., Cordeiro, I., Sousa, A. B., Lima, M., Soares, G., Rocha, M., Saraiva, J., Ramos, L., Sousa, S., Marcelino, J. P., Correia, A., Santos, H. G. <strong>Clinical and molecular diagnosis of the skeletal dysplasias associated with mutations in the gene encoding fibroblast growth factor receptor 3 (FGFR3) in Portugal.</strong> Clin. Genet. 75: 150-156, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19215249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19215249</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2008.01123.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19215249">Almeida et al. (2009)</a> reported a Portuguese patient with Muenke syndrome resulting from the P250R mutation who developed an osteochondroma in the proximal metaphysis of the left tibia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19215249" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a cohort of 182 Spanish probands with craniosynostosis, <a href="#83" class="mim-tip-reference" title="Paumard-Hernandez, B., Berges-Soria, J., Barroso, E., Rivera-Pedroza, C. I., Perez-Carrizosa, V., Benito-Sanz, S., Lopez-Messa, E., Santos, F., Garcia-Recuero, I. I., Romance, A., Ballesta-Martinez, M. J., Lopez-Gonzalez, V., Campos-Barros, A., Cruz, J., Guillen-Navarro, E., Sanchez del Pozo, J., Lapunzina, P., Garcia-Minaur, S., Heath, K. E. <strong>Expanding the mutation spectrum in 182 Spanish probands with craniosynostosis: identification and characterization of novel TCF12 variants.</strong> Europ. J. Hum. Genet. 23: 907-914, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25271085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25271085</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25271085[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2014.205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25271085">Paumard-Hernandez et al. (2015)</a> found the most frequent mutation to be P250R in FGFR3, which was detected in 24 patients (13.2% of the cohort). The authors noted that this was somewhat lower than the 24% detected in a UK study of craniosynostosis patients by <a href="#132" class="mim-tip-reference" title="Wilkie, A. O. M., Byren, J. C., Hurst, J. A., Jayamohan, J., Johnson, D., Knight, S. J. L., Lester, T., Richards, P. G., Twigg, S. R. F., Wall, S. A. <strong>Prevalence and complications of single-gene and chromosomal disorders in craniosynostosis.</strong> Pediatrics 126: e391-e400, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20643727/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20643727</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20643727[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/10.1542/peds.2009-3491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20643727">Wilkie et al. (2010)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20643727+25271085" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0015" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 ACHONDROPLASIA, SEVERE, WITH DEVELOPMENTAL DELAY AND ACANTHOSIS NIGRICANS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
THANATOPHORIC DYSPLASIA, TYPE I, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, LYS650MET
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121913105 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913105;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=rs121913105" 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=rs121913105" 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=RCV000017750 OR RCV001574416 OR RCV002310592 OR RCV002496392 OR RCV004558267" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017750, RCV001574416, RCV002310592, RCV002496392, RCV004558267" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017750...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated patients, <a href="#26" class="mim-tip-reference" title="Francomano, C. A., Bellus, G. A., Szabo, J., McIntosh, I., Dorst, J., Lee, R., Hurko, O., Fraley, A. E., Bamshad, M. J. <strong>A new skeletal dysplasia with severe tibial bowing, profound developmental delay and acanthosis nigricans is caused by a Lys 650 Met mutation in fibroblast growth factor receptor 3 (FGFR3). (Abstract)</strong> Am. J. Hum. Genet. 59 (suppl.): A25 only, 1996."None>Francomano et al. (1996)</a> found the same novel FGFR3 mutation as the cause of a previously undescribed skeletal dysplasia characterized by extreme short stature, severe tibial bowing, profound developmental delay, and acanthosis nigricans (SADDAN; <a href="/entry/616482">616482</a>). The mutation, a 1949A-T transversion causing a lys650-to-met (K650M) substitution, occurs in the distal tyrosine kinase domain. (A change at the adjacent nucleotide in FGFR3 (1948A-G) causes a substitution at the same codon (K650E; <a href="#0004">134934.0004</a>) and results in thanatophoric dysplasia type II (<a href="/entry/187601">187601</a>).) Both individuals with the K650M mutation, one aged 5 years and the other aged 29 years, had skeletal findings distinct from both TD1 (<a href="/entry/187600">187600</a>) and TD2. These included absence of craniosynostosis or cloverleaf skull anomaly and presence of moderate bowing of the femurs with reverse bowing of the tibia and fibula. The older patient had bilateral tibial pseudoarthroses. Other clinical and physical features common to both patients included survival past infancy; periods of respiratory compromise during infancy but without the need for prolonged mechanical ventilation; development of acanthosis nigricans in the cervical and flexural areas; and seizures and hydrocephalus during infancy with severe limitation of motor and intellectual development. The younger patient had structural anomalies of the brain, including a hypoplastic corpus callosum and abnormal development of the cerebellum.</p><p><a href="#118" class="mim-tip-reference" title="Tavormina, P. L., Bellus, G. A., Webster, M. K., Bamshad, M. J., Fraley, A. E., McIntosh, I., Szabo, J., Jiang, W., Jabs, E. W., Wilcox, W. R., Wasmuth, J. J., Donoghue, D. J., Thompson, L. M., Francomano, C. A. <strong>A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a lys650-to-met mutation in the fibroblast growth factor receptor 3 gene.</strong> Am. J. Hum. Genet. 64: 722-731, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10053006/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10053006</a>] [<a href="https://doi.org/10.1086/302275" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10053006">Tavormina et al. (1999)</a> referred to the distinctive syndrome described by <a href="#26" class="mim-tip-reference" title="Francomano, C. A., Bellus, G. A., Szabo, J., McIntosh, I., Dorst, J., Lee, R., Hurko, O., Fraley, A. E., Bamshad, M. J. <strong>A new skeletal dysplasia with severe tibial bowing, profound developmental delay and acanthosis nigricans is caused by a Lys 650 Met mutation in fibroblast growth factor receptor 3 (FGFR3). (Abstract)</strong> Am. J. Hum. Genet. 59 (suppl.): A25 only, 1996."None>Francomano et al. (1996)</a> as SADDAN dysplasia, an acronym derived from 'severe achondroplasia with developmental delay and acanthosis nigricans.' They reported 4 unrelated individuals with this syndrome (2 of whom were reported by <a href="#26" class="mim-tip-reference" title="Francomano, C. A., Bellus, G. A., Szabo, J., McIntosh, I., Dorst, J., Lee, R., Hurko, O., Fraley, A. E., Bamshad, M. J. <strong>A new skeletal dysplasia with severe tibial bowing, profound developmental delay and acanthosis nigricans is caused by a Lys 650 Met mutation in fibroblast growth factor receptor 3 (FGFR3). (Abstract)</strong> Am. J. Hum. Genet. 59 (suppl.): A25 only, 1996."None>Francomano et al., 1996</a>) approaching the severity observed in thanatophoric dysplasia type I. Different from thanatophoric dysplasia was the development of extensive areas of acanthosis nigricans beginning in early childhood in 3 patients, severe neurologic impairments, and survival past infancy without prolonged life-support measures. Lys650 is highly conserved in the kinase domain activation loop. Transient transfection studies with FGFR3 mutant constructs showed that the lys650-to-met mutation caused a dramatic increase in constitutive receptor kinase activity, approximately 3 times greater than that observed with the lys650-to-glu mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10053006" 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="#137" class="mim-tip-reference" title="Zankl, A., Elakis, G., Susman, R. D., Inglis, G., Gardener, G., Buckley, M. F., Roscioli, T. <strong>Prenatal and postnatal presentation of severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) due to the FGFR3 lys650met mutation.</strong> Am. J. Med. Genet. 146A: 212-218, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18076102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18076102</a>] [<a href="https://doi.org/10.1002/ajmg.a.32085" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18076102">Zankl et al. (2008)</a> reported a patient with the SADDAN phenotype associated with a K650M substitution resulting from a de novo 1949A-T transversion in exon 15 of the FGFR3 gene. The patient had severe micromelia, frontal bossing, large anterior fontanel, depressed nasal bridge, reverse tibial bowing, small thorax, and hypotonia. Acanthosis nigricans was not present. He died at age 21 days due to respiratory failure. <a href="#137" class="mim-tip-reference" title="Zankl, A., Elakis, G., Susman, R. D., Inglis, G., Gardener, G., Buckley, M. F., Roscioli, T. <strong>Prenatal and postnatal presentation of severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) due to the FGFR3 lys650met mutation.</strong> Am. J. Med. Genet. 146A: 212-218, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18076102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18076102</a>] [<a href="https://doi.org/10.1002/ajmg.a.32085" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18076102">Zankl et al. (2008)</a> noted that about half of patients reported with the K650M mutation died before 21 days of age, while others have shown longer survival. The authors also noted that acanthosis nigricans has been reported in patients with other skeletal dysplasias due to FGFR3 mutations, and thus should be considered a long-term complication rather than a specific feature of SADDAN. In addition, mental retardation only becomes apparent in long-term survivors and thus cannot be used as a diagnostic criterion for SADDAN in the neonatal period. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18076102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The K650M mutation due to a 1988A-T transversion was found in cell lines and tumors of multiple myeloma (<a href="/entry/254500">254500</a>) containing a karyotypically silent translocation between t(4;14) and the IgH. <a href="#16" class="mim-tip-reference" title="Chesi, M., Nardini, E., Brents, L. A., Schrock, E., Ried, T., Kuehl, W. M., Bergsagel, P. L. <strong>Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3.</strong> Nature Genet. 16: 260-264, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9207791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9207791</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9207791[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng0797-260" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9207791">Chesi et al. (1997)</a> proposed that after the t(4;14) translocation, somatic mutation during tumor progression generated an FGFR3 protein that was active in the absence of ligand. FGFR is, then, another example of a gene that can be both an oncogene and a 'teratogene.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9207791" 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="#55" class="mim-tip-reference" title="Kitoh, H., Brodie, S. G., Kupke, K. G., Lachman, R. S., Wilcox, W. R. <strong>Lys650-to-met substitution in the tyrosine kinase domain of the fibroblast growth factor receptor gene causes thanatophoric dysplasia type I. (Abstract)</strong> Hum. Mutat. 12: 362-363, 1998."None>Kitoh et al. (1998)</a> reported the lys650-to-met mutation as the cause of thanatophoric dysplasia type I.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0016" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, TYR373CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121913485 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913485;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=rs121913485" 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=rs121913485" 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=RCV000017751 OR RCV000255235 OR RCV003155034 OR RCV004737157" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017751, RCV000255235, RCV003155034, RCV004737157" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017751...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#98" class="mim-tip-reference" title="Rousseau, F., El Ghouzzi, V., Delezoide, A. L., Legeai-Mallet, L., Le Merrer, M., Munnich, A., Bonaventure, J. <strong>Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1).</strong> Hum. Molec. Genet. 5: 509-512, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845844</a>] [<a href="https://doi.org/10.1093/hmg/5.4.509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845844">Rousseau et al. (1996)</a> found a tyr373-to-cys mutation (Y373C) in the FGFR3 gene accounting, together with 2 other mutations, for 73% of 26 cases of thanatophoric dysplasia type I (TD1; <a href="/entry/187600">187600</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845844" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Brodie, S. G., Kitoh, H., Lipson, M., Sifry-Platt, M., Wilcox, W. R. <strong>Thanatophoric dysplasia type I with syndactyly.</strong> Am. J. Med. Genet. 80: 260-262, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9843049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9843049</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(19981116)80:3<260::aid-ajmg15>3.0.co;2-s" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9843049">Brodie et al. (1998)</a> reported a patient with TD1 due to the Y373C mutation in FGFR3, who had soft tissue syndactyly of the fingers and toes. Syndactyly had not previously been described in thanatophoric dysplasia or other conditions with FGFR3 mutations, although it occurs in several craniosynostosis syndromes due to mutations in FGFR2 (<a href="/entry/176943">176943</a>), notably Apert syndrome (<a href="/entry/101200">101200</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9843049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0017" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 MULTIPLE MYELOMA, SOMATIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, FGFR3/IGH FUSION
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000017752" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017752" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017752</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#16" class="mim-tip-reference" title="Chesi, M., Nardini, E., Brents, L. A., Schrock, E., Ried, T., Kuehl, W. M., Bergsagel, P. L. <strong>Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3.</strong> Nature Genet. 16: 260-264, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9207791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9207791</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9207791[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng0797-260" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9207791">Chesi et al. (1997)</a> identified the translocation t(4;14)(p16.3;q32.3) in 5 myeloma cell lines and in at least 3 of 10 primary tumors. Two cell lines and 1 primary tumor with this translocation selectively expressed an FGFR3 allele containing activating mutations identified previously in forms of dwarfism. <a href="#16" class="mim-tip-reference" title="Chesi, M., Nardini, E., Brents, L. A., Schrock, E., Ried, T., Kuehl, W. M., Bergsagel, P. L. <strong>Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3.</strong> Nature Genet. 16: 260-264, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9207791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9207791</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9207791[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng0797-260" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9207791">Chesi et al. (1997)</a> proposed that after the t(4;14) translocation, somatic mutation in the FGFR3 gene during tumor progression frequently generates an FGFR3 protein that is active in the absence of ligand. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9207791" 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="0018" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, ASN540THR
|
|
</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> rs77722678 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs77722678;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/rs77722678?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=rs77722678" 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=rs77722678" 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=RCV000017753 OR RCV001549822" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017753, RCV001549822" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017753...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family in which members were affected with hypochondroplasia (HCH; <a href="/entry/146000">146000</a>) in 3 generations, <a href="#22" class="mim-tip-reference" title="Deutz-Terlouw, P. P., Losekoot, M., Aalfs, C. M., Hennekam, R. C. M., Bakker, E. <strong>Asn540thr substitution in the fibroblast growth factor receptor 3 tyrosine kinase domain causing hypochondroplasia.</strong> Hum. Mutat. Suppl. 1: S62-S65, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9452043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9452043</a>] [<a href="https://doi.org/10.1002/humu.1380110122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9452043">Deutz-Terlouw et al. (1998)</a> found an A-to-C transversion at nucleotide 1658 of the FGFR3 gene, predicted to result in an asn540-to-thr substitution. The index patient was a 35-year-old male with mild rhizomelic limb shortening, stocky build, mild frontal bossing, and some limitation of pronation and supination of the left elbow. His height was 160 cm, his span 155.5 cm, and his skull circumference 56 cm. Radiographic examination showed short femoral necks, generalized brachydactyly, and absence of normal widening of the spinal canal in the lumbar area. Clinical findings in 2 of his 3 children and in his mother were similar. One of the affected sons also showed learning disabilities. The clinical symptoms, including macrocephaly and lumbar hyperlordosis, were more pronounced in him than in the other affected family members. The same codon was involved as in the more common asn540-to-lys mutation (<a href="#0010">134934.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9452043" 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="0019" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, ILE538VAL
|
|
</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> rs80053154 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80053154;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/rs80053154?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=rs80053154" 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=rs80053154" 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=RCV000017754 OR RCV001269544 OR RCV004798734" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017754, RCV001269544, RCV004798734" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017754...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Swedish family in which 3 members had hypochondroplasia (HCH; <a href="/entry/146000">146000</a>), <a href="#33" class="mim-tip-reference" title="Grigelioniene, G., Hagenas, L., Eklof, O., Neumeyer, L., Haereid, P. E., Anvret, M. <strong>A novel missense mutation ile538-to-val in the fibroblast growth factor receptor 3 in hypochondroplasia. (Abstract)</strong> Hum. Mutat. 11: 333 only, 1998."None>Grigelioniene et al. (1998)</a> found an A-to-G transition at position 1651, predicting an ile538-to-val substitution in the FGFR3 protein. The substitution occurred at a position close to the mutations in the asn540 codon (<a href="#0010">134934.0010</a>, <a href="#0018">134934.0018</a>), in a stretch of 9 amino acids that is highly conserved among all human fibroblast growth factor receptors.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0020" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, LYS650ASN, 1950G-T
|
|
</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> rs28928868 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28928868;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/rs28928868?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=rs28928868" 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=rs28928868" 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=RCV000017755 OR RCV003556038" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017755, RCV003556038" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017755...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#9" class="mim-tip-reference" title="Bellus, G. A., Spector, E. B., Speiser, P. W., Weaver, C. A., Garber, A. T., Bryke, C. R., Israel, J., Rosengren, S. S., Webster, M. K., Donoghue, D. J., Francomano, C. A. <strong>Distinct missense mutations of the FGFR3 lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype.</strong> Am. J. Hum. Genet. 67: 1411-1421, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11055896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11055896</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11055896[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/316892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11055896">Bellus et al. (2000)</a> demonstrated a 1950G-T mutation and a 1950G-C (<a href="#0021">134934.0021</a>) mutation in patients with hypochondroplasia (HCH; <a href="/entry/146000">146000</a>); both mutations resulted in a lys650-to-asn amino acid substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11055896" 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="0021" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, LYS650ASN, 1950G-C
|
|
</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> rs28928868 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28928868;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/rs28928868?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=rs28928868" 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=rs28928868" 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=RCV000017756 OR RCV001269938 OR RCV002496393" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017756, RCV001269938, RCV002496393" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017756...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#9" class="mim-tip-reference" title="Bellus, G. A., Spector, E. B., Speiser, P. W., Weaver, C. A., Garber, A. T., Bryke, C. R., Israel, J., Rosengren, S. S., Webster, M. K., Donoghue, D. J., Francomano, C. A. <strong>Distinct missense mutations of the FGFR3 lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype.</strong> Am. J. Hum. Genet. 67: 1411-1421, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11055896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11055896</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11055896[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/316892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11055896">Bellus et al. (2000)</a> found a lys650-to-asn mutation as the cause of hypochondroplasia (HCH; <a href="/entry/146000">146000</a>), resulting from either 1950G-T (<a href="#0020">134934.0020</a>) or 1950G-C. Several physical and radiologic features of the patients with hypochondroplasia due to the lys650-to-asn mutation were significantly milder than those in individuals with the asn540-to-lys (<a href="#0010">134934.0010</a>) or lys650-to-met (<a href="#0015">134934.0015</a>) mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11055896" 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="0022" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
BLADDER CANCER, SOMATIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, LYS650GLN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000017757 OR RCV000144153 OR RCV002228032" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017757, RCV000144153, RCV002228032" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017757...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#9" class="mim-tip-reference" title="Bellus, G. A., Spector, E. B., Speiser, P. W., Weaver, C. A., Garber, A. T., Bryke, C. R., Israel, J., Rosengren, S. S., Webster, M. K., Donoghue, D. J., Francomano, C. A. <strong>Distinct missense mutations of the FGFR3 lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype.</strong> Am. J. Hum. Genet. 67: 1411-1421, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11055896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11055896</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11055896[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/316892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11055896">Bellus et al. (2000)</a> identified a 1948A-C transversion in the FGFR3 gene, predicting a lys650-to-gln (K650Q) amino acid substitution and causing hypochondroplasia (HCH; <a href="/entry/146000">146000</a>) in a form milder than that seen in individuals with the asn540-to-lys (<a href="#0010">134934.0010</a>) or lys650-to-met (<a href="#0015">134934.0015</a>) mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11055896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#40" class="mim-tip-reference" title="Heuertz, S., Le Merrer, M., Zabel, B., Wright, M., Legeai-Mallet, L., Cormier-Daire, V., Gibbs, L., Bonaventure, J. <strong>Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.</strong> Europ. J. Hum. Genet. 14: 1240-1247, 2006. Note: Erratum: Europ. J. Hum. Genet. 14: 1321 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16912704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16912704</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201700" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16912704">Heuertz et al. (2006)</a> identified the K560Q mutation in a patient with a moderate form of hypochondroplasia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16912704" 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="#58" class="mim-tip-reference" title="Leroy, J. G., Nuytinck, L., Lambert, J., Naeyaert, J.-M., Mortier, G. R. <strong>Acanthosis nigricans in a child with mild osteochondrodysplasia and K650Q mutation in the FGFR3 gene.</strong> Am. J. Med. Genet. 143A: 3144-3149, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18000903/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18000903</a>] [<a href="https://doi.org/10.1002/ajmg.a.31966" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18000903">Leroy et al. (2007)</a> identified the K650Q mutation in a patient with a mild form of hypochondroplasia who was also diagnosed with acanthosis nigricans at 8 years of age. <a href="#58" class="mim-tip-reference" title="Leroy, J. G., Nuytinck, L., Lambert, J., Naeyaert, J.-M., Mortier, G. R. <strong>Acanthosis nigricans in a child with mild osteochondrodysplasia and K650Q mutation in the FGFR3 gene.</strong> Am. J. Med. Genet. 143A: 3144-3149, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18000903/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18000903</a>] [<a href="https://doi.org/10.1002/ajmg.a.31966" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18000903">Leroy et al. (2007)</a> stated that the mutation is located in the second part (3-prime side) of the split tyrosine kinase domain in the intracellular portion of the single-pass transmembrane of the receptor and that it unfavorably modulates the receptor's physiologic downstream inhibitory signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18000903" 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="#108" class="mim-tip-reference" title="Sibley, K., Cuthbert-Heavens, D., Knowles, M. A. <strong>Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell carcinoma.</strong> Oncogene 20: 686-691, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11314002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11314002</a>] [<a href="https://doi.org/10.1038/sj.onc.1204110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11314002">Sibley et al. (2001)</a> found the same mutation, which they designated LYS652GLN (K652Q), in a transitional cell carcinoma of the bladder (<a href="/entry/109800">109800</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11314002" 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="0023" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, ASN540SER
|
|
</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> rs77722678 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs77722678;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/rs77722678?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=rs77722678" 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=rs77722678" 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=RCV000017758 OR RCV000623459 OR RCV001269614 OR RCV002262566 OR RCV002273934" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017758, RCV000623459, RCV001269614, RCV002262566, RCV002273934" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017758...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#73" class="mim-tip-reference" title="Mortier, G., Nuytinck, L., Craen, M., Renard, J.-P., Leroy, J. G., De Paepe, A. <strong>Clinical and radiographic features of a family with hypochondroplasia owing to a novel asn540ser mutation in the fibroblast growth factor receptor 3 gene.</strong> J. Med. Genet. 37: 220-224, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10777366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10777366</a>] [<a href="https://doi.org/10.1136/jmg.37.3.220" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10777366">Mortier et al. (2000)</a> reported a father and daughter with clinical and radiographic features of hypochondroplasia who were heterozygous for an A-to-G transition resulting in the replacement of an asparagine residue at position 540 by a serine residue (N540S). Both individuals were mildly affected. The father's height was between the 3rd and 25th centile; he had short limbs and relative macrocephaly. Radiographs showed definite features of hypochondroplasia. The daughter was below the 3rd centile in height with short limbs, frontal bossing, and lumbar hyperlordosis. Radiographic features were subtle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10777366" 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="#121" class="mim-tip-reference" title="Thauvin-Robinet, C., Faivre, L., Lewin, P., De Monleon, J.-V., Francois, C., Huet, F., Couailler, J.-F., Campos-Xavier, A. B., Bonaventure, J., Le Merrer, M. <strong>Hypochondroplasia and stature within normal limits: another family with an asn540-to-ser mutation in the fibroblast growth factor receptor 3 gene. (Letter)</strong> Am. J. Med. Genet. 119A: 81-84, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12707965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12707965</a>] [<a href="https://doi.org/10.1002/ajmg.a.10238" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12707965">Thauvin-Robinet et al. (2003)</a> described a family in which the N540S mutation was present in 2 brothers and their father. The proband was a 2-month-old boy referred for assessment of short limbs and macrocephaly. His brother, age 2.5 years, showed a height within the normal limits but macrocephaly with frontal bossing and mild micromelia were evident. Family history indicated micromelia and macrocephaly in the paternal grandfather (height, 163 cm) and the father's sister. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12707965" 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="0024" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 MOVED TO <a href="/entry/134934#0022">134934.0022</a></strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0025" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 COLORECTAL CANCER, SOMATIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, GLU322LYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121913111 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913111;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=rs121913111" 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=rs121913111" 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=RCV000017761" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017761" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017761</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a primary colorectal cancer (<a href="/entry/114500">114500</a>), <a href="#50" class="mim-tip-reference" title="Jang, J.-H., Shin, K.-H., Park, J.-G. <strong>Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers.</strong> Cancer Res. 61: 3541-3543, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11325814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11325814</a>]" pmid="11325814">Jang et al. (2001)</a> found a G-to-A transition in the FGFR3 gene, converting codon 322 from glu to lys. Glu322 is a highly conserved residue not only within the FGFR family but throughout evolution from yeast to human. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11325814" 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="0026" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 COLORECTAL CANCER, SOMATIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, 1-BP DEL, 849C
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776836 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776836;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=rs587776836" 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=rs587776836" 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=RCV000017762" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017762" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017762</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a primary colorectal cancer (<a href="/entry/114500">114500</a>), <a href="#50" class="mim-tip-reference" title="Jang, J.-H., Shin, K.-H., Park, J.-G. <strong>Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers.</strong> Cancer Res. 61: 3541-3543, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11325814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11325814</a>]" pmid="11325814">Jang et al. (2001)</a> found a 1-bp deletion (849delC) in exon 7 of the FGFR3 gene causing a frameshift and premature termination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11325814" 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="0027" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 ACHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, GLY380ARG AND LEU377ARG
|
|
</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> rs267606809 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606809;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/rs267606809?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=rs267606809" 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=rs267606809" 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=RCV000017724 OR RCV000017763 OR RCV000029207 OR RCV000255750 OR RCV000763121 OR RCV001266979 OR RCV001807732 OR RCV002231193 OR RCV002276551 OR RCV003227605 OR RCV004545731 OR RCV004783725 OR RCV004798732" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017724, RCV000017763, RCV000029207, RCV000255750, RCV000763121, RCV001266979, RCV001807732, RCV002231193, RCV002276551, RCV003227605, RCV004545731, RCV004783725, RCV004798732" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017724...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Dutch infant with a severe form of achondroplasia (ACH; <a href="/entry/100800">100800</a>), <a href="#100" class="mim-tip-reference" title="Rump, P., Letteboer, T. G. W., Gille, J. J. P., Torringa, M. J. L., Baerts, W., van Gestel, J. P. J., Verheij, J. B. G. M., van Essen, A. J. <strong>Severe complications in a child with achondroplasia and two FGFR3 mutations on the same allele.</strong> Am. J. Med. Genet. 140A: 284-290, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16411219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16411219</a>] [<a href="https://doi.org/10.1002/ajmg.a.31084" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16411219">Rump et al. (2006)</a> identified 2 de novo mutations in the FGFR3 gene on the same allele. One was the common G380R mutation (<a href="#0001">134934.0001</a>), and the other was a 1130T-G transversion, resulting in a leu377-to-arg (L377R) substitution within the transmembrane domain. Allele-specific PCR analysis confirmed that the 2 mutations were in cis. From birth, the child had severe respiratory difficulties with multiple hypoxic episodes due to a combination of upper airway obstruction, pulmonary hypoplasia, and cervicomedullary compression. He eventually became ventilator dependent and died at age 4 months. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16411219" 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="0028" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 LADD SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, ASP513ASN
|
|
</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> rs121913112 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913112;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/rs121913112?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=rs121913112" 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=rs121913112" 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=RCV001580446 OR RCV003226161 OR RCV004558268 OR RCV004786272" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001580446, RCV003226161, RCV004558268, RCV004786272" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001580446...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Turkish father and his 2 childen with LADD syndrome (LADD2; <a href="/entry/620192">620192</a>), <a href="#95" class="mim-tip-reference" title="Rohmann, E., Brunner, H. G., Kayserili, H., Uyguner, O., Nurnberg, G., Lew, E. D., Dobbie, A., Eswarakumar, V. P., Uzumcu, A., Ulubil-Emeroglu, M., Leroy, J. G., Li, Y., and 9 others. <strong>Mutations in different components of FGF signaling in LADD syndrome.</strong> Nature Genet. 38: 414-417, 2006. Note: Erratum: Nature Genet. 38: 495 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16501574/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16501574</a>] [<a href="https://doi.org/10.1038/ng1757" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16501574">Rohmann et al. (2006)</a> identified a heterozygous missense mutation in the FGFR3 gene: 1537G-A in exon 11, leading to an asn513-to-asn (D513N) substitution in the conserved tyrosine kinase-1 (TK1) domain. The mutation occurred de novo in the affected father and was subsequently transmitted to his affected offspring. The D513N mutation is located in a loop that connects the beta-3 sheet to the alpha-C helix of the tyrosine kinase core. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16501574" 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="0029" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 CAMPTODACTYLY, TALL STATURE, AND HEARING LOSS SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, ARG621HIS
|
|
</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> rs121913113 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913113;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/rs121913113?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=rs121913113" 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=rs121913113" 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=RCV000017765 OR RCV002228033" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017765, RCV002228033" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017765...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In all affected members of a family with CATSHL syndrome (CATSHL; <a href="/entry/610474">610474</a>), <a href="#123" class="mim-tip-reference" title="Toydemir, R. M., Brassington, A. E., Bayrak-Toydemir, P., Krakowiak, P. A., Jorde, L. B., Whitby, F. G., Longo, N., Viskochil, D. H., Carey, J. C., Bamshad, M. J. <strong>A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome.</strong> Am. J. Hum. Genet. 79: 935-941, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033969</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033969[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/508433" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033969">Toydemir et al. (2006)</a> identified heterozygosity for a 1862G-A transition in the FGFR3 gene, resulting in an arg621-to-his (R621H) substitution. The mutation occurred in the catalytic loop of the tyrosine kinase domain and predicted partial loss of protein function. The mutation was not found in any unaffected members of the family or in 500 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17033969" 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="0030" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 ACHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
HYPOCHONDROPLASIA, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, SER279CYS
|
|
</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> rs121913114 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913114;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/rs121913114?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=rs121913114" 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=rs121913114" 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=RCV000017766 OR RCV000017767 OR RCV000730955" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017766, RCV000017767, RCV000730955" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017766...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Achondroplasia</em></strong></p><p>
|
|
In a boy with achondroplasia (ACH; <a href="/entry/100800">100800</a>) who was negative for the common G380R mutation (<a href="#0001">134934.0001</a>), <a href="#40" class="mim-tip-reference" title="Heuertz, S., Le Merrer, M., Zabel, B., Wright, M., Legeai-Mallet, L., Cormier-Daire, V., Gibbs, L., Bonaventure, J. <strong>Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.</strong> Europ. J. Hum. Genet. 14: 1240-1247, 2006. Note: Erratum: Europ. J. Hum. Genet. 14: 1321 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16912704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16912704</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201700" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16912704">Heuertz et al. (2006)</a> identified heterozygosity for a de novo 835A-C transversion in exon 7 of the FGFR3 gene, resulting in an ser279-to-cys (S279C) substitution in the IgIIIa extracellular domain. In addition to the typical skeletal features of ACH, the child had epilepsy and moderate learning difficulties. Severe kyphoscoliosis required surgical correction at age 7 years, which was complicated by postoperative lower limb paralysis requiring decompressive surgery. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16912704" 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>Hypochondroplasia</em></strong></p><p>
|
|
<a href="#28" class="mim-tip-reference" title="Friez, M. J., Wilson, J. A. P. <strong>Novel FGFR3 mutations in exon 7 and implications for expanded screening of achondroplasia and hypochondroplasia: a response to Heuertz et al. (Letter)</strong> Europ. J. Hum. Genet. 16: 277-278, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17895900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17895900</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201931" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17895900">Friez and Wilson (2008)</a> identified the S279C mutation in a newborn originally diagnosed with achondroplasia whose phenotype evolved into a milder form of hypochondroplasia (HCH; <a href="/entry/146000">146000</a>) in early childhood. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17895900" 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="0031" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, TYR278CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121913115 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913115;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=rs121913115" 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=rs121913115" 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=RCV000017768 OR RCV000415056 OR RCV002513085" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017768, RCV000415056, RCV002513085" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017768...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 30-year-old woman with hypochondroplasia (HCH; <a href="/entry/146000">146000</a>), <a href="#40" class="mim-tip-reference" title="Heuertz, S., Le Merrer, M., Zabel, B., Wright, M., Legeai-Mallet, L., Cormier-Daire, V., Gibbs, L., Bonaventure, J. <strong>Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.</strong> Europ. J. Hum. Genet. 14: 1240-1247, 2006. Note: Erratum: Europ. J. Hum. Genet. 14: 1321 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16912704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16912704</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201700" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16912704">Heuertz et al. (2006)</a> identified heterozygosity for a de novo 833A-G transition in exon 7 of the FGFR3 gene, resulting in a tyr278-to-cys (Y278C) substitution in the IgIIIa extracellular domain. The patient was born with an achondroplasia-like phenotype which changed to typical hypochondroplasia with normal craniofacial features by 3.5 years of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16912704" 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="0032" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0032 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, SER84LEU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121913116 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913116;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=rs121913116" 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=rs121913116" 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=RCV000017769 OR RCV000850610 OR RCV001334259 OR RCV002513086" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017769, RCV000850610, RCV001334259, RCV002513086" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017769...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 4-generation family with a moderate hypochondroplasia phenotype (HCH; <a href="/entry/146000">146000</a>), <a href="#40" class="mim-tip-reference" title="Heuertz, S., Le Merrer, M., Zabel, B., Wright, M., Legeai-Mallet, L., Cormier-Daire, V., Gibbs, L., Bonaventure, J. <strong>Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.</strong> Europ. J. Hum. Genet. 14: 1240-1247, 2006. Note: Erratum: Europ. J. Hum. Genet. 14: 1321 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16912704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16912704</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201700" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16912704">Heuertz et al. (2006)</a> identified heterozygosity for a 251C-T transition in exon 3 of the FGFR3 gene, resulting in a ser84-to-leu (S84L) substitution in the IgI extracellular domain. The mutation was not found in unaffected family members. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16912704" 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="0033" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0033 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
NEVUS, EPIDERMAL, SOMATIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, GLY370CYS
|
|
</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> rs121913479 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913479;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/rs121913479?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=rs121913479" 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=rs121913479" 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=RCV000017770 OR RCV000029208 OR RCV000413645 OR RCV003493410 OR RCV003989295 OR RCV004668734 OR RCV005025064" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017770, RCV000029208, RCV000413645, RCV003493410, RCV003989295, RCV004668734, RCV005025064" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017770...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Thanatophoric Dysplasia, Type I</em></strong></p><p>
|
|
<a href="#98" class="mim-tip-reference" title="Rousseau, F., El Ghouzzi, V., Delezoide, A. L., Legeai-Mallet, L., Le Merrer, M., Munnich, A., Bonaventure, J. <strong>Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1).</strong> Hum. Molec. Genet. 5: 509-512, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845844</a>] [<a href="https://doi.org/10.1093/hmg/5.4.509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845844">Rousseau et al. (1996)</a> identified a gly370-to-cys (G370C) mutation accounting for 1 of 26 cases of thanatophoric dysplasia type I (TD1; <a href="/entry/187600">187600</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845844" 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>Nevus, Epidermal, Somatic</em></strong></p><p>
|
|
<a href="#35" class="mim-tip-reference" title="Hafner, C., van Oers, J. M. M., Vogt, T., Landthaler, M., Stoehr, R., Blaszyk, H., Hofstaedter, F., Zwarthoff, E. C., Hartmann, A. <strong>Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi.</strong> J. Clin. Invest. 116: 2201-2207, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16841094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16841094</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16841094[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/10.1172/JCI28163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16841094">Hafner et al. (2006)</a> analyzed the FGFR3 gene in 39 common epidermal nevi (<a href="/entry/162900">162900</a>) from 33 patients and identified mosaicism for a double mutation in exon 10 of the FGFR3 gene in 1 patient: the G372C mutation and the G382R (G380R; <a href="#0001">134934.0001</a>) mutation. Codons were numbered according to the FGFR3 IIIb isoform. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16841094" 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="0034" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0034 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, ASN540LYS AND GLN485ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267606808 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606808;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=rs267606808" 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=rs267606808" 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=RCV000017740 OR RCV000017771 OR RCV000255928 OR RCV000353403 OR RCV002273932 OR RCV004541008 OR RCV004786271" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000017740, RCV000017771, RCV000255928, RCV000353403, RCV002273932, RCV004541008, RCV004786271" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000017740...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a fetus with lethal thanatophoric dysplasia I (TD1; <a href="/entry/187600">187600</a>), <a href="#81" class="mim-tip-reference" title="Pannier, S., Martinovic, J., Heuertz, S., Delezoide, A.-L., Munnich, A., Schibler, L., Serre, V., Legeai-Mallet, L. <strong>Thanatophoric dysplasia caused by double missense FGFR3 mutations.</strong> Am. J. Med. Genet. 149A: 1296-1301, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19449430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19449430</a>] [<a href="https://doi.org/10.1002/ajmg.a.32880" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19449430">Pannier et al. (2009)</a> identified 2 de novo heterozygous mutations in the FGFR3 gene on the same allele: N540K (<a href="#0010">134934.0010</a>), and a 1454A-G transition, resulting in a gln485-to-arg (Q485R) substitution at a conserved residue in the beta-2 strand in the kinase domain. Protein modeling suggested that the mutations altered the receptor structure, holding it in a fully activated state, consistent with a gain of function. The pregnancy was terminated at 24 weeks' gestation after the fetus was noted to have severe dwarfism. Radiographic studies showed severe rhizomelic shortness of the long bones and mild bowing of the femora, radii, and ulnae. The spine showed severe platyspondyly with H-shaped vertebrae and narrowing of the interpediculate distance. The thorax was small with short ribs, and the iliac bones were short and wide. Macrocrania and frontal bossing were observed; there was no evidence of a cloverleaf skull. Postmortem examination showed cerebral cortical malformations and severe disorganization of growth plates in the long bones. The N540K mutation in isolation usually results in the less severe phenotype of hypochondroplasia (HCH; <a href="/entry/146000">146000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19449430" 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="0035" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0035 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, ALA334THR
|
|
</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> rs373496046 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs373496046;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/rs373496046?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=rs373496046" 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=rs373496046" 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=RCV000022552" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022552" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022552</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant is classified as a variant of unknown significance because its contribution to a craniosynostosis phenotype has not been confirmed.</p><p>In a Spanish boy with mild isolated craniosynostosis, but an inconclusive skull radiograph, <a href="#5" class="mim-tip-reference" title="Barroso, E., Perez-Carrizosa, V., Garcia-Recuero, I., Glucksman, M. J., Wilkie, A. O., Garcia-Minaur, S., Heath, K. E. <strong>Mild isolated craniosynostosis due to a novel FGFR3 mutation, p.Ala334Thr.</strong> Am. J. Med. Genet. 155A: 3050-3053, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22038757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22038757</a>] [<a href="https://doi.org/10.1002/ajmg.a.34199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22038757">Barroso et al. (2011)</a> identified a heterozygous 1000G-A transition in exon 8 of the FGFR3 gene, resulting in an ala334-to-thr (A334T) substitution at a conserved residue just before the beta-F loop of the IgIII domain of FGFR3C. The mutation was not found in 188 Spanish control individuals. The proband, who was delivered prematurely at 29 weeks' gestation, was noted at birth to have turri/brachycephaly with caput succedaneum. However, the cranial deformity corrected itself within the first 4 months of life and he showed normal psychomotor development. At age 5.5 years, he had a disproportionately large head compared to his body, but head circumference was in the normal range. His head appeared slightly scaphocephalic, he had a tall, broad forehead with a slightly prominent metopic suture, and mild hypertelorism with somewhat downward slanting palpebral fissures. The mother, who also carried the A334T variant, had even milder features, with a high, broad forehead, apparent mild hypertelorism, and the appearance of a large head, but normal head circumference. The maternal grandfather, who also carried the variant, had similar cranial features to the mother, but measurements were not done. All had normal height. No functional studies on the A334T variant were performed. <a href="#5" class="mim-tip-reference" title="Barroso, E., Perez-Carrizosa, V., Garcia-Recuero, I., Glucksman, M. J., Wilkie, A. O., Garcia-Minaur, S., Heath, K. E. <strong>Mild isolated craniosynostosis due to a novel FGFR3 mutation, p.Ala334Thr.</strong> Am. J. Med. Genet. 155A: 3050-3053, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22038757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22038757</a>] [<a href="https://doi.org/10.1002/ajmg.a.34199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22038757">Barroso et al. (2011)</a> suggested that the A334T variant was responsible for the phenotype because the equivalent variant in FGFR2, A337T (<a href="/entry/176943#0042">176943.0042</a>), was found in a proband with unicoronal synostosis; however, that variant was also found in 6 unaffected members of the proband's family (<a href="#131" class="mim-tip-reference" title="Wilkie, A. O. M., Bochukova, E. G., Hansen, R. M. S., Taylor, I. B., Rannan-Eliya, S. V., Byren, J. C., Wall, S. A., Ramos, L., Venancio, M., Hurst, J. A., O'Rourke, A. W., Williams, L. J., Seller, A., Lester, T. <strong>Clinical dividends from the molecular genetic diagnosis of craniosynostosis.</strong> Am. J. Med. Genet. 143A: 1941-1949, 2007. Note: Republication with correction of an article originally published in Am. J. Med. Genet. 140A: 2631-2639, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17621648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17621648</a>] [<a href="https://doi.org/10.1002/ajmg.a.31905" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17621648">Wilkie et al., 2007</a>). <a href="#5" class="mim-tip-reference" title="Barroso, E., Perez-Carrizosa, V., Garcia-Recuero, I., Glucksman, M. J., Wilkie, A. O., Garcia-Minaur, S., Heath, K. E. <strong>Mild isolated craniosynostosis due to a novel FGFR3 mutation, p.Ala334Thr.</strong> Am. J. Med. Genet. 155A: 3050-3053, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22038757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22038757</a>] [<a href="https://doi.org/10.1002/ajmg.a.34199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22038757">Barroso et al. (2011)</a> noted that another FGFR2 variant at the same residue (A337P; <a href="/entry/176943#0041">176943.0041</a>) was found in a patient with Crouzon syndrome (<a href="/entry/123500">123500</a>), again suggesting that the FGFR3 A334T variant may have pathogenic potential. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17621648+22038757" 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="0036" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0036 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, GLY342CYS
|
|
</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> rs587778775 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587778775;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/rs587778775?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=rs587778775" 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=rs587778775" 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=RCV000056066" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056066" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056066</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 25-year-old Chinese woman with hypochondroplasia (HCH; <a href="/entry/146000">146000</a>) who had short extremities, relative macrocephaly, frontal bossing, and genu varum, <a href="#129" class="mim-tip-reference" title="Wang, H., Sun, Y., Wu, W., Wei, X., Lan, Z., Xie, J. <strong>A novel missense mutation of FGFR3 in a Chinese female and her fetus with hypochondroplasia by next-generation sequencing.</strong> Clin. Chim. Acta 423: 62-65, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23726269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23726269</a>] [<a href="https://doi.org/10.1016/j.cca.2013.04.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23726269">Wang et al. (2013)</a> identified a heterozygous c.1024G-T transversion in the FGFR3 gene, resulting in a gly342-to-cys (G342C) substitution at a conserved residue in the IgIII loop. The mutation was found by exome sequencing and confirmed by Sanger sequencing. The mutation was also found in the woman's fetus after ultrasound showed abnormally short femur at 28 weeks' gestation. The unaffected father did not have the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23726269" 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="0037" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0037 CAMPTODACTYLY, TALL STATURE, AND HEARING LOSS SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, THR546LYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587777857 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777857;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=rs587777857" 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=rs587777857" 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=RCV000144699" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000144699" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000144699</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers, born of consanguineous Egyptian parents, with camptodactyly, tall stature, and hearing loss (CATSHL; <a href="/entry/610474">610474</a>), <a href="#65" class="mim-tip-reference" title="Makrythanasis, P., Temtamy, S., Aglan, M., Otaify, G. A., Hamamy, H., Antonarakis, S. E. <strong>A novel homozygous mutation in FGFR3 causes tall stature, severe lateral tibial deviation, scoliosis, hearing impairment, camptodactyly, and arachnodactyly.</strong> Hum. Mutat. 35: 959-963, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24864036/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24864036</a>] [<a href="https://doi.org/10.1002/humu.22597" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24864036">Makrythanasis et al. (2014)</a> identified a homozygous c.1637C-A transversion in exon 12 of the FGFR3 gene, resulting in a thr546-to-lys (T546K) substitution at a conserved residue in the protein kinase domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was filtered against the dbSNP (build 135), 1000 Genomes Project, and Exome Variant Server databases and was not found in 50 control individuals of the same ethnic origin. Functional studies of the variant were not performed, but the authors postulated a loss-of-function effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24864036" 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="0038" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0038 LADD SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
FGFR3, ASP628ASN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1453271838 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1453271838;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=rs1453271838" 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=rs1453271838" 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=RCV004559335 OR RCV004597852" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV004559335, RCV004597852" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV004559335...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 23-year-old proband and his affected mother in a consanguineous Iranian family with LADD syndrome (LADD2; <a href="/entry/620192">620192</a>), <a href="#117" class="mim-tip-reference" title="Talebi, F., Ghanbari Mardasi, F., Mohammadi Asl, J., Bavarsad, A. H., Tizno, S. <strong>Identification of a novel missence (sic) mutation in FGFR3 gene in an Iranian family with LADD syndrome by next-generation sequencing.</strong> Int. J. Pediat. Otorhinolaryng. 97: 192-196, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28483234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28483234</a>] [<a href="https://doi.org/10.1016/j.ijporl.2017.04.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28483234">Talebi et al. (2017)</a> identified a heterozygous c.1882G-A transition in exon 14 of the FGFR3 gene, resulting in an asp628-to-asn (D628N) substitution at a highly conserved residue in the cytoplasmic tyrosine kinase domain. The mutation, which was found by next-generation sequencing and confirmed by Sanger sequencing, was not present in the unaffected father or in 400 control chromosomes. No functional studies were reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28483234" 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="Almeida2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Almeida, M. R., Campos-Xavier, A. B., Medeira, A., Cordeiro, I., Sousa, A. B., Lima, M., Soares, G., Rocha, M., Saraiva, J., Ramos, L., Sousa, S., Marcelino, J. P., Correia, A., Santos, H. G.
|
|
<strong>Clinical and molecular diagnosis of the skeletal dysplasias associated with mutations in the gene encoding fibroblast growth factor receptor 3 (FGFR3) in Portugal.</strong>
|
|
Clin. Genet. 75: 150-156, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19215249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19215249</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19215249" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2008.01123.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Angle1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Angle, B., Hersh, J. H., Christensen, K. M.
|
|
<strong>Molecularly proven hypochondroplasia with cloverleaf skull deformity: a novel association.</strong>
|
|
Clin. Genet. 54: 417-420, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9842995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9842995</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9842995" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1998.tb03756.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Arnaud-Lopez2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Arnaud-Lopez, L., Fragoso, R., Mantilla-Capacho, J., Barros-Nunez, P.
|
|
<strong>Crouzon with acanthosis nigricans: further delineation of the syndrome.</strong>
|
|
Clin. Genet. 72: 405-410, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17935505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17935505</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17935505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.2007.00884.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Avraham1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Avraham, K. B., Givol, D., Avivi, A., Yayon, A., Copeland, N. G., Jenkins, N. A.
|
|
<strong>Mapping of murine fibroblast growth factor receptors refines regions of homology between mouse and human chromosomes.</strong>
|
|
Genomics 21: 656-658, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7959747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7959747</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7959747" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1994.1330" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Barroso2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Barroso, E., Perez-Carrizosa, V., Garcia-Recuero, I., Glucksman, M. J., Wilkie, A. O., Garcia-Minaur, S., Heath, K. E.
|
|
<strong>Mild isolated craniosynostosis due to a novel FGFR3 mutation, p.Ala334Thr.</strong>
|
|
Am. J. Med. Genet. 155A: 3050-3053, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22038757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22038757</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22038757" 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.34199" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Bellus1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bellus, G. A., Gaudenz, K., Zackai, E. H., Clarke, L. A., Szabo, J., Francomano, C. A., Muenke, M.
|
|
<strong>Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes.</strong>
|
|
Nature Genet. 14: 174-176, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8841188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8841188</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8841188" 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/ng1096-174" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Bellus1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bellus, G. A., Hefferon, T. W., Ortiz de Luna, R. I., Hecht, J. T., Horton, W. A., Machado, M., Kaitila, I., McIntosh, I., Francomano, C. A.
|
|
<strong>Achondroplasia is defined by recurrent G380R mutations of FGFR3.</strong>
|
|
Am. J. Hum. Genet. 56: 368-373, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7847369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7847369</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7847369" 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="8" class="mim-anchor"></a>
|
|
<a id="Bellus1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bellus, G. A., McIntosh, I., Smith, E. A., Aylsworth, A. S., Kaitila, I., Horton, W. A., Greenhaw, G. A., Hecht, J. T., Francomano, C. A.
|
|
<strong>A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia.</strong>
|
|
Nature Genet. 10: 357-359, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670477/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670477</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670477" 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/ng0795-357" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Bellus2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bellus, G. A., Spector, E. B., Speiser, P. W., Weaver, C. A., Garber, A. T., Bryke, C. R., Israel, J., Rosengren, S. S., Webster, M. K., Donoghue, D. J., Francomano, C. A.
|
|
<strong>Distinct missense mutations of the FGFR3 lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype.</strong>
|
|
Am. J. Hum. Genet. 67: 1411-1421, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11055896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11055896</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11055896[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=11055896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/316892" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Bergsagel1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bergsagel, P. L., Chesi, M., Nardini, E., Brents, L. A., Kirby, S. L., Kuehl, W. M.
|
|
<strong>Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 13931-13936, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8943038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8943038</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=8943038[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=8943038" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.93.24.13931" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Brodie1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brodie, S. G., Kitoh, H., Lachman, R. S., Nolasco, L. M., Mekikian, P. B., Wilcox, W. R.
|
|
<strong>Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by FGFR3 mutations.</strong>
|
|
Am. J. Med. Genet. 84: 476-480, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10360402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10360402</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10360402" 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="12" class="mim-anchor"></a>
|
|
<a id="Brodie1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brodie, S. G., Kitoh, H., Lipson, M., Sifry-Platt, M., Wilcox, W. R.
|
|
<strong>Thanatophoric dysplasia type I with syndactyly.</strong>
|
|
Am. J. Med. Genet. 80: 260-262, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9843049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9843049</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9843049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(sici)1096-8628(19981116)80:3<260::aid-ajmg15>3.0.co;2-s" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Cappellen1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cappellen, D., De Oliveira, C., Ricol, D., Gil Diez de Medina, S., Bourdin, J., Sastre-Garau, X., Chopin, D., Thiery, J. P., Radvanyi, F.
|
|
<strong>Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. (Letter)</strong>
|
|
Nature Genet. 23: 18-20, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10471491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10471491</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10471491" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/12615" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Chen1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, L., Adar, R., Yang, X., Monsonego, E. O., Li, C., Hauschka, P. V., Yayon, A., Deng, C.-X.
|
|
<strong>Gly369-to-cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis.</strong>
|
|
J. Clin. Invest. 104: 1517-1525, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10587515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10587515</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10587515[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=10587515" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI6690" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Chen2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, L., Li, C., Qiao, W., Xu, X., Deng, C.
|
|
<strong>A ser365-cys mutation of fibroblast growth factor receptor 3 in mouse downregulates Ihh/PTHrP signals and causes severe achondroplasia.</strong>
|
|
Hum. Molec. Genet. 10: 457-465, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11181569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11181569</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11181569" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/10.5.457" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Chesi1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chesi, M., Nardini, E., Brents, L. A., Schrock, E., Ried, T., Kuehl, W. M., Bergsagel, P. L.
|
|
<strong>Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3.</strong>
|
|
Nature Genet. 16: 260-264, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9207791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9207791</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9207791[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=9207791" 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/ng0797-260" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Chitayat1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chitayat, D., Fernandez, B., Gardner, A., Moore, L., Glance, P., Dunn, M., Chun, K., Sgro, M., Ray, P., Allingham-Hawkins, D.
|
|
<strong>Compound heterozygosity for the achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome.</strong>
|
|
Am. J. Med. Genet. 84: 401-405, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10360393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10360393</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10360393" 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="18" class="mim-anchor"></a>
|
|
<a id="Cho2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cho, J. Y., Guo, C., Torello, M., Lunstrum, G. P., Iwata, T., Deng, C., Horton, W. A.
|
|
<strong>Defective lysosomal targeting of activated fibroblast growth factor receptor 3 in achondroplasia.</strong>
|
|
Proc. Nat. Acad. Sci. 101: 609-614, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14699054/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14699054</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14699054[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=14699054" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.2237184100" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Colvin1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Colvin, J. S., Bohne, B. A., Harding, G. W., McEwen, D. G., Ornitz, D. M.
|
|
<strong>Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3.</strong>
|
|
Nature Genet. 12: 390-397, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8630492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8630492</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8630492" 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/ng0496-390" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Davidson2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Davidson, D., Blanc, A., Filion, D., Wang, H., Plut, P., Pfeffer, G., Buschmann, M. D., Henderson, J. E.
|
|
<strong>Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis.</strong>
|
|
J. Biol. Chem. 280: 20509-20515, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15781473/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15781473</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15781473" 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.M410148200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Deng1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Deng, C., Wynshaw-Boris, A., Zhou, F., Kuo, A., Leder, P.
|
|
<strong>Fibroblast growth factor receptor 3 is a negative regulator of bone growth.</strong>
|
|
Cell 84: 911-921, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8601314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8601314</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8601314" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0092-8674(00)81069-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Deutz-Terlouw1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Deutz-Terlouw, P. P., Losekoot, M., Aalfs, C. M., Hennekam, R. C. M., Bakker, E.
|
|
<strong>Asn540thr substitution in the fibroblast growth factor receptor 3 tyrosine kinase domain causing hypochondroplasia.</strong>
|
|
Hum. Mutat. Suppl. 1: S62-S65, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9452043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9452043</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9452043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.1380110122" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="El Ghouzzi1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
El Ghouzzi, V., Lajeunie, E., Le Merrer, M., Cormier-Daire, V., Renier, D., Munnich, A., Bonaventure, J.
|
|
<strong>Mutations within or upstream of the basic helix-loop-helix domain of the TWIST gene are specific to Saethre-Chotzen syndrome.</strong>
|
|
Europ. J. Hum. Genet. 7: 27-33, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10094188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10094188</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10094188" 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/sj.ejhg.5200240" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Eswarakumar2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eswarakumar, V. P., Schlessinger, J.
|
|
<strong>Skeletal overgrowth is mediated by deficiency in a specific isoform of fibroblast growth factor receptor 3.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 3937-3942, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360456</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360456[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=17360456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0700012104" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Fofanova1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fofanova, O. V., Takamura, N., Kinoshita, E., Meerson, E. M., Iljina, V. K., Nechvolodova, O. L., Evgrafov, O. V., Peterkova, V. A., Yamashita, S.
|
|
<strong>A missense mutation of C1659 in the fibroblast growth factor receptor 3 gene in Russian patients with hypochondroplasia.</strong>
|
|
Endocr. J. 45: 791-795, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10395236/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10395236</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10395236" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1507/endocrj.45.791" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Francomano1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Francomano, C. A., Bellus, G. A., Szabo, J., McIntosh, I., Dorst, J., Lee, R., Hurko, O., Fraley, A. E., Bamshad, M. J.
|
|
<strong>A new skeletal dysplasia with severe tibial bowing, profound developmental delay and acanthosis nigricans is caused by a Lys 650 Met mutation in fibroblast growth factor receptor 3 (FGFR3). (Abstract)</strong>
|
|
Am. J. Hum. Genet. 59 (suppl.): A25 only, 1996.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Frattini2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Frattini, V., Pagnotta, S. M., Tala, Fan, J. J., Russo, M. V., Lee, S. B., Garofano, L., Zhang, J., Shi, P., Lewis, G., Sanson, H., Frederick, V., and 11 others.
|
|
<strong>A metabolic function of FGFR3-TACC3 gene fusions in cancer.</strong>
|
|
Nature 553: 222-227, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29323298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29323298</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29323298[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=29323298" 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/nature25171" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Friez2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Friez, M. J., Wilson, J. A. P.
|
|
<strong>Novel FGFR3 mutations in exon 7 and implications for expanded screening of achondroplasia and hypochondroplasia: a response to Heuertz et al. (Letter)</strong>
|
|
Europ. J. Hum. Genet. 16: 277-278, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17895900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17895900</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17895900" 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/sj.ejhg.5201931" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Garcia-Vargas2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Garcia-Vargas, A., Hafner, C., Perez-Rodriguez, A. G., Rodriguez-Rojas, L. X., Gonzalez-Esqueda, P., Stoehr, R., Hernandez-Torres, M., Happle, R.
|
|
<strong>An epidermal nevus syndrome with cerebral involvement caused by a mosaic FGFR3 mutation.</strong>
|
|
Am. J. Med. Genet. 146A: 2275-2279, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18642369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18642369</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18642369" 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.32429" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Golla1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Golla, A., Lichmer, P., von Gernet, S., Winterpacht, A., Fairley, J., Murken, J., Schuffenhauer, S.
|
|
<strong>Phenotypic expression of the fibroblast growth factor receptor 3 (FGFR3) mutation P250R in a large craniosynostosis family.</strong>
|
|
J. Med. Genet. 34: 683-684, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9279764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9279764</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9279764" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.34.8.683" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Goriely2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goriely, A., Hansen, R. M. S., Taylor, I. B., Olesen, I. A., Jacobsen, G. K., McGowan, S. J., Pfeifer, S. P., McVean, G. A. T., Rajpert-De Meyts, E., Wilkie, A. O. M.
|
|
<strong>Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors.</strong>
|
|
Nature Genet. 41: 1247-1252, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19855393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19855393</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19855393[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=19855393" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng.470" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Graham1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Graham, J. M., Jr., Braddock, S. R., Mortier, G. R., Lachman, R., Van Dop, C., Jabs, E. W.
|
|
<strong>Syndrome of coronal craniosynostosis with brachydactyly and carpal tarsal coalition due to Pro250Arg mutation in FGFR3 gene.</strong>
|
|
Am. J. Med. Genet. 77: 322-329, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9600744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9600744</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9600744" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(sici)1096-8628(19980526)77:4<322::aid-ajmg14>3.0.co;2-k" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Grigelioniene1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Grigelioniene, G., Hagenas, L., Eklof, O., Neumeyer, L., Haereid, P. E., Anvret, M.
|
|
<strong>A novel missense mutation ile538-to-val in the fibroblast growth factor receptor 3 in hypochondroplasia. (Abstract)</strong>
|
|
Hum. Mutat. 11: 333 only, 1998.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Gripp1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gripp, K. W., McDonald-McGinn, D. M., Gaudenz, K., Whitaker, L. A., Bartlett, S. P., Glat, P. M., Cassileth, L. B., Mayro, R., Zackai, E. H., Muenke, M.
|
|
<strong>Identification of a genetic cause for isolated unilateral coronal synostosis: a unique mutation in the fibroblast growth factor receptor 3.</strong>
|
|
J. Pediat. 132: 714-716, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9580776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9580776</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9580776" 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/s0022-3476(98)70366-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Hafner2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hafner, C., van Oers, J. M. M., Vogt, T., Landthaler, M., Stoehr, R., Blaszyk, H., Hofstaedter, F., Zwarthoff, E. C., Hartmann, A.
|
|
<strong>Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi.</strong>
|
|
J. Clin. Invest. 116: 2201-2207, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16841094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16841094</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16841094[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=16841094" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI28163" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="He2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
He, L., Horton, W., Hristova, K.
|
|
<strong>Physical basis behind achondroplasia, the most common form of human dwarfism.</strong>
|
|
J. Biol. Chem. 285: 30103-30114, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20624921/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20624921</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20624921[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=20624921" 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.M109.094086" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="He2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
He, L., Shobnam, N., Wimley, W. C., Hristova, K.
|
|
<strong>FGFR3 heterodimerization in achondroplasia, the most common form of human dwarfism.</strong>
|
|
J. Biol. Chem. 286: 13272-13281, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21324899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21324899</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21324899[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=21324899" 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.M110.205583" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Henderson2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Henderson, J. E., Naski, M. C., Aarts, M. M., Wang, D., Cheng, L., Goltzman, D., Ornitz, D. M.
|
|
<strong>Expression of FGFR3 with the G380R achondroplasia mutation inhibits proliferation and maturation of CFK2 chondrocytic cells.</strong>
|
|
J. Bone Miner. Res. 15: 155-165, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10646125/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10646125</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10646125" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1359/jbmr.2000.15.1.155" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Henderson2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Henderson, S., Sillence, D., Loughlin, J., Bennetts, B., Sykes, B.
|
|
<strong>Germline and somatic mosaicism in achondroplasia.</strong>
|
|
J. Med. Genet. 37: 956-958, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11186939/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11186939</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11186939" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.37.12.956" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Heuertz2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Heuertz, S., Le Merrer, M., Zabel, B., Wright, M., Legeai-Mallet, L., Cormier-Daire, V., Gibbs, L., Bonaventure, J.
|
|
<strong>Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.</strong>
|
|
Europ. J. Hum. Genet. 14: 1240-1247, 2006. Note: Erratum: Europ. J. Hum. Genet. 14: 1321 only, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16912704/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16912704</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16912704" 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/sj.ejhg.5201700" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Hollway1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hollway, G. E., Suthers, G. K., Battese, K. M., Turner, A. M., David, D. J., Mulley, J. C.
|
|
<strong>Deafness due to pro250-to-arg mutation of FGFR3. (Letter)</strong>
|
|
Lancet 351: 877-878, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9525367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9525367</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9525367" 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/S0140-6736(98)24012-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Huggins1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Huggins, M. J., Smith, J. R., Chun, K., Ray, P. N., Shah, J. K., Whelan, D. T.
|
|
<strong>Achondroplasia-hypochondroplasia complex in a newborn infant.</strong>
|
|
Am. J. Med. Genet. 84: 396-400, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10360392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10360392</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10360392" 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="43" class="mim-anchor"></a>
|
|
<a id="Hyland2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hyland, V. J., Robertson, S. P., Flanagan, S., Savarirayan, R., Roscioli, T., Masel, J., Hayes, M., Glass, I. A.
|
|
<strong>Somatic and germline mosaicism for a R248C missense mutation in FGFR3, resulting in a skeletal dysplasia distinct from thanatophoric dysplasia.</strong>
|
|
Am. J. Med. Genet. 120A: 157-168, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12833394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12833394</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12833394" 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.20012" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Ibrahimi2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ibrahimi, O. A., Zhang, F., Eliseenkova, A. V., Linhardt, R. J., Mohammadi, M.
|
|
<strong>Proline to arginine mutations in FGF receptors 1 and 3 result in Pfeiffer and Muenke craniosynostosis syndromes through enhancement of FGF binding affinity.</strong>
|
|
Hum. Molec. Genet. 13: 69-78, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14613973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14613973</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14613973" 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/ddh011" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Ikegawa1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ikegawa, S., Fukushima, Y., Isomura, M., Takada, F., Nakamura, Y.
|
|
<strong>Mutations of the fibroblast growth factor receptor-3 gene in one familial and six sporadic cases of achondroplasia in Japanese patients.</strong>
|
|
Hum. Genet. 96: 309-311, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7649548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7649548</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7649548" 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/BF00210413" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Intini2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Intini, D., Baldini, L., Fabris, S., Lombardi, L., Ciceri, G., Maiolo, A. T., Neri, A.
|
|
<strong>Analysis of FGFR3 gene mutations in multiple myeloma patients with t(4;14).</strong>
|
|
Brit. J. Haemat. 114: 362-364, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11529856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11529856</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11529856" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2141.2001.02957.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Iwata2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Iwata, T., Chen, L., Li, C., Ovchinnikov, D. A., Behringer, R. R., Francomano, C. A., Deng, C.-X.
|
|
<strong>A neonatal lethal mutation in FGFR3 uncouples proliferation and differentiation of growth plate chondrocytes in embryos.</strong>
|
|
Hum. Molec. Genet. 9: 1603-1613, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10861287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10861287</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10861287" 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/9.11.1603" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Iwata2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Iwata, T., Li, C.-L., Deng, C.-X., Francomano, C. A.
|
|
<strong>Highly activated Fgfr3 with the K644M mutation causes prolonged survival in severe dwarf mice.</strong>
|
|
Hum. Molec. Genet. 10: 1255-1264, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11406607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11406607</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11406607" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/10.12.1255" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Jacky2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jacky, B. P. S., Garay, P. E., Dupuy, J., Nelson, J. B., Cai, B., Molina, Y., Wang, J., Steward, L. E., Broide, R. S., Francis, J., Aoki, K. R., Stevens, R. C., Fernandez-Salas, E.
|
|
<strong>Identification of fibroblast growth factor receptor 3 (FGFR3) as a protein receptor for botulinum neurotoxin serotype A (BoNT/A).</strong>
|
|
PLoS Pathog. 9: e1003369, 2013. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23696738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23696738</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23696738[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=23696738" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1371/journal.ppat.1003369" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="50" class="mim-anchor"></a>
|
|
<a id="Jang2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jang, J.-H., Shin, K.-H., Park, J.-G.
|
|
<strong>Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers.</strong>
|
|
Cancer Res. 61: 3541-3543, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11325814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11325814</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11325814" 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="51" class="mim-anchor"></a>
|
|
<a id="Jang2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jang, J.-H.
|
|
<strong>Identification and characterization of soluble isoform of fibroblast growth factor receptor 3 in human SaOS-2 osteosarcoma cells.</strong>
|
|
Biochem. Biophys. Res. Commun. 292: 378-382, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11906172/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11906172</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11906172" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/bbrc.2002.6668" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Karoui2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Karoui, M., Hofmann-Radvanyi, H., Zimmermann, U., Couvelard, A., Degott, C., Faridoni-Laurens, L., Ahomadegbe, J.-C., Gazzeri, S., Brambilla, E., Clerici, T., Charbonnier, P., Tresallet, C., and 8 others.
|
|
<strong>No evidence of somatic FGFR3 mutation in various types of carcinoma.</strong>
|
|
Oncogene 20: 5059-5061, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11526491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11526491</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11526491" 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/sj.onc.1204651" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Keegan1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Keegan, K., Johnson, D. E., Williams, L. T., Hayman, M. J.
|
|
<strong>Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 1095-1099, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1847508/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1847508</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1847508" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.88.4.1095" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Kimura2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kimura, T., Suzuki, H., Ohashi, T., Kiyota, H., Eto, Y.
|
|
<strong>The incidence of thanatophoric dysplasia mutations in FGFR3 bladder carcinomas.</strong>
|
|
Cancer 92: 2555-2561, 2001. Note: Erratum: Cancer 94: 2117 only, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11745189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11745189</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11745189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/1097-0142(20011115)92:10<2555::aid-cncr1607>3.0.co;2-m" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Kitoh1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kitoh, H., Brodie, S. G., Kupke, K. G., Lachman, R. S., Wilcox, W. R.
|
|
<strong>Lys650-to-met substitution in the tyrosine kinase domain of the fibroblast growth factor receptor gene causes thanatophoric dysplasia type I. (Abstract)</strong>
|
|
Hum. Mutat. 12: 362-363, 1998.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="56" class="mim-anchor"></a>
|
|
<a id="Lajeunie1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lajeunie, E., El Ghouzzi, V., Le Merrer, M., Munnich, A., Bonaventure, J., Renier, D.
|
|
<strong>Sex related expressivity of the phenotype in coronal craniosynostosis caused by the recurrent P250R FGFR3 mutation.</strong>
|
|
J. Med. Genet. 36: 9-13, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9950359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9950359</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9950359" 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="57" class="mim-anchor"></a>
|
|
<a id="Lanning1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lanning, R. W., Brown, C. A.
|
|
<strong>An improved methodology for the detection of the common mutation in the FGFR3 gene responsible for achondroplasia.</strong>
|
|
Hum. Mutat. 10: 496-499, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9401015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9401015</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9401015" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1098-1004(1997)10:6<496::AID-HUMU13>3.0.CO;2-V" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="58" class="mim-anchor"></a>
|
|
<a id="Leroy2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Leroy, J. G., Nuytinck, L., Lambert, J., Naeyaert, J.-M., Mortier, G. R.
|
|
<strong>Acanthosis nigricans in a child with mild osteochondrodysplasia and K650Q mutation in the FGFR3 gene.</strong>
|
|
Am. J. Med. Genet. 143A: 3144-3149, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18000903/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18000903</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18000903" 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.31966" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="59" class="mim-anchor"></a>
|
|
<a id="Li1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, C., Chen, L., Iwata, T., Kitagawa, M., Fu, X.-Y., Deng, C.-X.
|
|
<strong>A Lys644Glu substitution in fibroblast growth factor receptor 3 (FGFR3) causes dwarfism in mice by activation of STATs and ink4 cell cycle inhibitors.</strong>
|
|
Hum. Molec. Genet. 8: 35-44, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9887329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9887329</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9887329" 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/8.1.35" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="60" class="mim-anchor"></a>
|
|
<a id="Li2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, D., Liao, C., Ma, X., Li, Q., Tang, X.
|
|
<strong>Thanatophoric dysplasia type 2 with encephalocele during the second trimester.</strong>
|
|
Am. J. Med. Genet. 140A: 1476-1477, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16752380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16752380</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16752380" 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.31293" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="61" class="mim-anchor"></a>
|
|
<a id="Lievens2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lievens, P. M.-J., Liboi, E.
|
|
<strong>The thanatophoric dysplasia type II mutation hampers complete maturation of fibroblast growth factor receptor 3 (FGFR3), which activates signal transducer and activator of transcription 1 (STAT1) from the endoplasmic reticulum.</strong>
|
|
J. Biol. Chem. 278: 17344-17349, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12624096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12624096</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12624096" 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.M212710200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="62" class="mim-anchor"></a>
|
|
<a id="Lin2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lin, T., Sandusky, S. B., Xue, H., Fishbein, K. W., Spencer, R. G., Rao, M. S., Francomano, C. A.
|
|
<strong>A central nervous system specific mouse model for thanatophoric dysplasia type II.</strong>
|
|
Hum. Molec. Genet. 12: 2863-2871, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12966031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12966031</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12966031" 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/ddg309" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="63" class="mim-anchor"></a>
|
|
<a id="Logie2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Logie, A., Dunois-Larde, C., Rosty, C., Levrel, O., Blanche, M., Ribeiro, A., Gasc, J.-M., Jorcano, J., Werner, S., Sastre-Garau, X., Thiery, J. P., Radvanyi, F.
|
|
<strong>Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans.</strong>
|
|
Hum. Molec. Genet. 14: 1153-1160, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15772091/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15772091</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15772091" 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/ddi127" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="64" class="mim-anchor"></a>
|
|
<a id="Lowry2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lowry, R. B., Jabs, E. W., Graham, G. E., Gerritsen, J., Fleming, J.
|
|
<strong>Syndrome of coronal craniosynostosis, Klippel-Feil anomaly, and Sprengel shoulder with and without pro250arg mutation in the FGFR3 gene.</strong>
|
|
Am. J. Med. Genet. 104: 112-119, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11746040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11746040</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11746040" 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.10049" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="65" class="mim-anchor"></a>
|
|
<a id="Makrythanasis2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Makrythanasis, P., Temtamy, S., Aglan, M., Otaify, G. A., Hamamy, H., Antonarakis, S. E.
|
|
<strong>A novel homozygous mutation in FGFR3 causes tall stature, severe lateral tibial deviation, scoliosis, hearing impairment, camptodactyly, and arachnodactyly.</strong>
|
|
Hum. Mutat. 35: 959-963, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24864036/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24864036</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24864036" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.22597" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="66" class="mim-anchor"></a>
|
|
<a id="Mansour2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mansour, S. L., Twigg, S. R. F., Freeland, R. M., Wall, S. A., Li, C., Wilkie, A. O. M.
|
|
<strong>Hearing loss in a mouse model of Muenke syndrome.</strong>
|
|
Hum. Molec. Genet. 18: 43-50, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18818193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18818193</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18818193[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=18818193" 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/ddn311" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="67" class="mim-anchor"></a>
|
|
<a id="Matsushita2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matsushita, T., Wilcox, W. R., Chan, Y. Y., Kawanami, A., Bukulmez, H., Balmes, G., Krejci, P., Mekikian, P. B., Otani, K., Yamaura, I., Warman, M. L., Givol, D., Murakami, S.
|
|
<strong>FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway.</strong>
|
|
Hum. Molec. Genet. 18: 227-240, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18923003/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18923003</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18923003[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=18923003" 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/ddn339" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="68" class="mim-anchor"></a>
|
|
<a id="McKusick1973" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McKusick, V. A., Kelly, T. E., Dorst, J. P.
|
|
<strong>Observations suggesting allelism of the achondroplasia and hypochondroplasia genes.</strong>
|
|
J. Med. Genet. 10: 11-16, 1973.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4697848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4697848</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4697848" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.10.1.11" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="69" class="mim-anchor"></a>
|
|
<a id="Meyers1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meyers, G. A., Orlow, S. J., Munro, I. R., Przylepa, K. A., Jabs, E. W.
|
|
<strong>Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans.</strong>
|
|
Nature Genet. 11: 462-464, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7493034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7493034</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7493034" 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/ng1295-462" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="70" class="mim-anchor"></a>
|
|
<a id="Moloney1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Moloney, D. M., Slaney, S. F., Oldridge, M., Wall, S. A., Sahlin, P., Stenman, G., Wilkie, A. O. M.
|
|
<strong>Exclusive paternal origin of new mutations in Apert syndrome.</strong>
|
|
Nature Genet. 13: 48-53, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8673103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8673103</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8673103" 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/ng0596-48" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="71" class="mim-anchor"></a>
|
|
<a id="Moloney1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Moloney, D. M., Wall, S. A., Ashworth, G. J., Oldridge, M., Glass, I. A., Francomano, C. A., Muenke, M., Wilkie, A. O. M.
|
|
<strong>Prevalence of pro250arg mutation of fibroblast growth factor receptor 3 in coronal craniosynostosis.</strong>
|
|
Lancet 349: 1059-1062, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9107244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9107244</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9107244" 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/s0140-6736(96)09082-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="72" class="mim-anchor"></a>
|
|
<a id="Monsonego-Ornan2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Monsonego-Ornan, E., Adar, R., Feferman, T., Segev, O., Yayon, A.
|
|
<strong>The transmembrane mutation G380R in fibroblast growth factor receptor 3 uncouples ligand-mediated receptor activation from down-regulation.</strong>
|
|
Molec. Cell. Biol. 20: 516-522, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10611230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10611230</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10611230[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=10611230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/MCB.20.2.516-522.2000" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="73" class="mim-anchor"></a>
|
|
<a id="Mortier2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mortier, G., Nuytinck, L., Craen, M., Renard, J.-P., Leroy, J. G., De Paepe, A.
|
|
<strong>Clinical and radiographic features of a family with hypochondroplasia owing to a novel asn540ser mutation in the fibroblast growth factor receptor 3 gene.</strong>
|
|
J. Med. Genet. 37: 220-224, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10777366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10777366</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10777366" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.37.3.220" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="74" class="mim-anchor"></a>
|
|
<a id="Muenke1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Muenke, M., Gripp, K. W., McDonald-McGinn, D. M., Gaudenz, K., Whitaker, L. A., Bartlett, S. P., Markowitz, R. I., Robin, N. H., Nwokoro, N., Mulvihill, J. J., Losken, W., Mulliken, J. B., Guttmacher, A. E., Wilroy, R. S., Clarke, L. A., Hollway, G., Ades, L. C., Haan, E. A., Mulley, J. C., Cohen, M. M., Jr., Bellus, G. A., Francomano, C. A., Moloney, D. M., Wall, S. A., Wilkie, A. O. M., Zackai, E. H.
|
|
<strong>A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome.</strong>
|
|
Am. J. Hum. Genet. 60: 555-564, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9042914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9042914</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9042914" 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="75" class="mim-anchor"></a>
|
|
<a id="Naski1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Naski, M. C., Colvin, J. S., Coffin, J. D., Ornitz, D. M.
|
|
<strong>Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3.</strong>
|
|
Development 125: 4977-4988, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9811582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9811582</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9811582" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1242/dev.125.24.4977" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="76" class="mim-anchor"></a>
|
|
<a id="Naski1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Naski, M. C., Wang, Q., Xu, J., Ornitz, D. M.
|
|
<strong>Graded activation of fibroblast growth factor receptor 3 by mutations causing achondroplasia and thanatophoric dysplasia.</strong>
|
|
Nature Genet. 13: 233-237, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8640234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8640234</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8640234" 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/ng0696-233" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="77" class="mim-anchor"></a>
|
|
<a id="Natacci2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Natacci, F., Baffico, M., Cavallari, U., Bedeschi, M. F., Mura, I., Paffoni, A., Setti, P. L., Baldi, M., Lalatta, F.
|
|
<strong>Germline mosaicism in achondroplasia detected in sperm DNA of the father of three affected sibs.</strong>
|
|
Am. J. Med. Genet. 146A: 784-786, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18266238/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18266238</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18266238" 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.32228" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="78" class="mim-anchor"></a>
|
|
<a id="Nishimura1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nishimura, G., Fukushima, Y., Ohashi, H., Ikegawa, S.
|
|
<strong>Atypical radiological findings in achondroplasia with uncommon mutation of the fibroblast growth factor receptor-3 (FGFR-3) gene (gly to cys transition at codon 375). (Letter)</strong>
|
|
Am. J. Med. Genet. 59: 393-395, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8599370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8599370</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8599370" 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.1320590325" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="79" class="mim-anchor"></a>
|
|
<a id="Nishimura1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nishimura, G., Takada, F.
|
|
<strong>Another observation of atypical radiologic findings in achondroplasia not due to a common mutation of the FGFR-3 gene: reply to Dr. Gorlin. (Letter)</strong>
|
|
Am. J. Med. Genet. 70: 203-205, 1997.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="80" class="mim-anchor"></a>
|
|
<a id="Nowroozi2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nowroozi, N., Raffioni, S., Wang, T., Apostol, B. L., Bradshaw, R. A., Thompson, L. M.
|
|
<strong>Sustained ERK1/2 but not STAT1 or 3 activation is required for thanatophoric dysplasia phenotypes in PC12 cells.</strong>
|
|
Hum. Molec. Genet. 14: 1529-1538, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15843401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15843401</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15843401" 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/ddi161" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="81" class="mim-anchor"></a>
|
|
<a id="Pannier2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pannier, S., Martinovic, J., Heuertz, S., Delezoide, A.-L., Munnich, A., Schibler, L., Serre, V., Legeai-Mallet, L.
|
|
<strong>Thanatophoric dysplasia caused by double missense FGFR3 mutations.</strong>
|
|
Am. J. Med. Genet. 149A: 1296-1301, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19449430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19449430</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19449430" 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.32880" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="82" class="mim-anchor"></a>
|
|
<a id="Passos-Bueno1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Passos-Bueno, M. R., Wilcox, W. R., Jabs, E. W., Sertie, A. L., Alonso, L. G., Kitoh, H.
|
|
<strong>Clinical spectrum of fibroblast growth factor receptor mutations.</strong>
|
|
Hum. Mutat. 14: 115-125, 1999. Note: Erratum: Hum. Mutat. 17: 431 only, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10425034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10425034</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10425034" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)14:2<115::AID-HUMU3>3.0.CO;2-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="83" class="mim-anchor"></a>
|
|
<a id="Paumard-Hernandez2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Paumard-Hernandez, B., Berges-Soria, J., Barroso, E., Rivera-Pedroza, C. I., Perez-Carrizosa, V., Benito-Sanz, S., Lopez-Messa, E., Santos, F., Garcia-Recuero, I. I., Romance, A., Ballesta-Martinez, M. J., Lopez-Gonzalez, V., Campos-Barros, A., Cruz, J., Guillen-Navarro, E., Sanchez del Pozo, J., Lapunzina, P., Garcia-Minaur, S., Heath, K. E.
|
|
<strong>Expanding the mutation spectrum in 182 Spanish probands with craniosynostosis: identification and characterization of novel TCF12 variants.</strong>
|
|
Europ. J. Hum. Genet. 23: 907-914, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25271085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25271085</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25271085[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=25271085" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ejhg.2014.205" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="84" class="mim-anchor"></a>
|
|
<a id="Paznekas1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Paznekas, W. A., Cunningham, M. L., Howard, T. D., Korf, B. R., Lipson, M. H., Grix, A. W., Feingold, M., Goldberg, R., Borochowitz, Z., Aleck, K., Mulliken, J., Yin, M., Jabs, E. W.
|
|
<strong>Genetic heterogeneity of Saethre-Chotzen syndrome, due to TWIST and FGFR mutations.</strong>
|
|
Am. J. Hum. Genet. 62: 1370-1380, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9585583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9585583</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9585583" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/301855" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="85" class="mim-anchor"></a>
|
|
<a id="Perez-Castro1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Perez-Castro, A. V., Wilson, J., Altherr, M. R.
|
|
<strong>Genomic organization of the human fibroblast growth factor receptor 3 (FGFR3) gene and comparative sequence analysis with the mouse Fgfr3 gene.</strong>
|
|
Genomics 41: 10-16, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9126476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9126476</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9126476" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1997.4616" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="86" class="mim-anchor"></a>
|
|
<a id="Pokharel1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pokharel, R. K., Alimsardjono, H., Takeshima, Y., Nakamura, H., Naritomi, K., Hirose, S., Onishi, S., Matsuo, M.
|
|
<strong>Japanese cases of type 1 thanatophoric dysplasia exclusively carry a C to T transition at nucleotide 742 of the fibroblast growth factor receptor 3 gene.</strong>
|
|
Biochem. Biophys. Res. Commun. 227: 236-239, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8858131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8858131</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8858131" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/bbrc.1996.1495" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="87" class="mim-anchor"></a>
|
|
<a id="Prinos1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Prinos, P., Costa, T., Sommer, A., Kilpatrick, M. W., Tsipouras, P.
|
|
<strong>A common FGFR3 gene mutation in hypochondroplasia.</strong>
|
|
Hum. Molec. Genet. 4: 2097-2101, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589686/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589686</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8589686" 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/4.11.2097" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="88" class="mim-anchor"></a>
|
|
<a id="Prinster1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Prinster, C., Carrera, P., Del Maschio, M., Weber, G., Maghnie, M., Vigone, M. C., Mora, S., Tonini, G., Rigon, F., Beluffi, G., Severi, F., Chiumello, G., Ferrari, M.
|
|
<strong>Comparison of clinical-radiological and molecular findings in hypochondroplasia.</strong>
|
|
Am. J. Med. Genet. 75: 109-112, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9450868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9450868</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9450868" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(sici)1096-8628(19980106)75:1<109::aid-ajmg22>3.0.co;2-p" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="89" class="mim-anchor"></a>
|
|
<a id="Ramaswami1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ramaswami, U., Rumsby, G., Hindmarsh, P. C., Brook, C. G. D.
|
|
<strong>Genotype and phenotype in hypochondroplasia.</strong>
|
|
J. Pediat. 133: 99-102, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9672519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9672519</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9672519" 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/s0022-3476(98)70186-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="90" class="mim-anchor"></a>
|
|
<a id="Rannan-Eliya2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rannan-Eliya, S. V., Taylor, I. B., de Heer, I. M., van den Ouweland, A. M. W., Wall, S. A., Wilkie, A. O. M.
|
|
<strong>Paternal origin of FGFR3 mutations in Muenke-type craniosynostosis.</strong>
|
|
Hum. Genet. 115: 200-207, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15241680/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15241680</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15241680" 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/s00439-004-1151-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="91" class="mim-anchor"></a>
|
|
<a id="Rasmussen2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rasmussen, T., Hudlebusch, H. R., Knudsen, L. M., Johnsen, H. E.
|
|
<strong>FGFR3 dysregulation in multiple myeloma: frequency and prognostic relevance.</strong>
|
|
Brit. J. Haemat. 117: 626-628, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12028033/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12028033</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12028033" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1046/j.1365-2141.2002.03429.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="92" class="mim-anchor"></a>
|
|
<a id="Reardon1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reardon, W., Wilkes, D., Rutland, P., Pulleyn, L. J., Malcolm, S., Dean, J. C. S., Evans, R. D., Jones, B. M., Hayward, R., Hall, C. M., Nevin, N. C., Baraitser, M., Winter, R. M.
|
|
<strong>Craniosynostosis associated with FGFR3 pro250-to-arg mutation results in a range of clinical presentations including unisutural sporadic craniosynostosis.</strong>
|
|
J. Med. Genet. 34: 632-636, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9279753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9279753</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9279753" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.34.8.632" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="93" class="mim-anchor"></a>
|
|
<a id="Riley2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Riley, B. M., Mansilla, M. A., Ma, J., Daack-Hirsch, S., Maher, B. S., Raffensperger, L. M., Russo, E. T., Vieira, A. R., Dode, C., Mohammadi, M., Marazita, M. L., Murray, J. C.
|
|
<strong>Impaired FGF signaling contributes to cleft lip and palate.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 4512-4517, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17360555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17360555</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17360555[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=17360555" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0607956104" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="94" class="mim-anchor"></a>
|
|
<a id="Robin1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Robin, N. H., Scott, J. A., Cohen, A. R., Goldstein, J. A.
|
|
<strong>Nonpenetrance in FGFR3-associated coronal synostosis syndrome. (Letter)</strong>
|
|
Am. J. Med. Genet. 80: 296-297, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9843059/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9843059</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9843059" 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="95" class="mim-anchor"></a>
|
|
<a id="Rohmann2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rohmann, E., Brunner, H. G., Kayserili, H., Uyguner, O., Nurnberg, G., Lew, E. D., Dobbie, A., Eswarakumar, V. P., Uzumcu, A., Ulubil-Emeroglu, M., Leroy, J. G., Li, Y., and 9 others.
|
|
<strong>Mutations in different components of FGF signaling in LADD syndrome.</strong>
|
|
Nature Genet. 38: 414-417, 2006. Note: Erratum: Nature Genet. 38: 495 only, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16501574/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16501574</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16501574" 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/ng1757" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="96" class="mim-anchor"></a>
|
|
<a id="Roscioli2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Roscioli, T., Flanagan, S., Mortimore, R. J., Kumar, P., Weedon, D., Masel, J., Lewandowski, R., Hyland, V., Glass, I. A.
|
|
<strong>Premature calvarial synostosis and epidermal hyperplasia (Beare-Stevenson syndrome-like anomalies) resulting from a P250R missense mutation in the gene encoding fibroblast growth factor receptor 3.</strong>
|
|
Am. J. Med. Genet. 101: 187-194, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11424131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11424131</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11424131" 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.1369" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="97" class="mim-anchor"></a>
|
|
<a id="Rousseau1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rousseau, F., Bonaventure, J., Legeai-Mallet, L., Pelet, A., Rozet, J.-M., Maroteaux, P., Le Merrer, M., Munnich, A.
|
|
<strong>Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.</strong>
|
|
Nature 371: 252-254, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8078586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8078586</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8078586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/371252a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="98" class="mim-anchor"></a>
|
|
<a id="Rousseau1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rousseau, F., El Ghouzzi, V., Delezoide, A. L., Legeai-Mallet, L., Le Merrer, M., Munnich, A., Bonaventure, J.
|
|
<strong>Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1).</strong>
|
|
Hum. Molec. Genet. 5: 509-512, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845844</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845844" 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/5.4.509" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="99" class="mim-anchor"></a>
|
|
<a id="Rousseau1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rousseau, F., Saugier, P., Le Merrer, M., Munnich, A., Delezoide, A.-L., Maroteaux, P., Bonaventure, J., Narcy, F., Sanak, M.
|
|
<strong>Stop codon FGFR3 mutations in thanatophoric dwarfism type 1.</strong>
|
|
Nature Genet. 10: 11-12, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7647778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7647778</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7647778" 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/ng0595-11" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="100" class="mim-anchor"></a>
|
|
<a id="Rump2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rump, P., Letteboer, T. G. W., Gille, J. J. P., Torringa, M. J. L., Baerts, W., van Gestel, J. P. J., Verheij, J. B. G. M., van Essen, A. J.
|
|
<strong>Severe complications in a child with achondroplasia and two FGFR3 mutations on the same allele.</strong>
|
|
Am. J. Med. Genet. 140A: 284-290, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16411219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16411219</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16411219" 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.31084" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="101" class="mim-anchor"></a>
|
|
<a id="Saito2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Saito, H., Sekizawa, A., Morimoto, T., Suzuki, M., Yanaihara, T.
|
|
<strong>Prenatal DNA diagnosis of a single-gene disorder from maternal plasma.</strong>
|
|
Lancet 356: 1170 only, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11030304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11030304</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11030304" 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/S0140-6736(00)02767-7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="102" class="mim-anchor"></a>
|
|
<a id="Salazar2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Salazar, L., Kashiwada, T., Krejci, P., Muchowski, P., Donoghue, D., Wilcox, W. R., Thompson, L. M.
|
|
<strong>A novel interaction between fibroblast growth factor receptor 3 and the p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation of ERK by p85 in multiple myeloma cells.</strong>
|
|
Hum. Molec. Genet. 18: 1951-1961, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19286672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19286672</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19286672[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=19286672" 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/ddp116" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="103" class="mim-anchor"></a>
|
|
<a id="Sawai1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sawai, H., Komori, S., Ida, A., Henmi, T., Bessho, T., Koyama, K.
|
|
<strong>Prenatal diagnosis of thanatophoric dysplasia by mutational analysis of the fibroblast growth factor receptor 3 gene and a proposed correction of previously published PCR results.</strong>
|
|
Prenatal Diag. 19: 21-24, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10073901/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10073901</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10073901" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(sici)1097-0223(199901)19:1<21::aid-pd457>3.0.co;2-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="104" class="mim-anchor"></a>
|
|
<a id="Scotet1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Scotet, E., Houssaint, E.
|
|
<strong>The choice between alternative IIIb and IIIc exons of the FGFR-3 gene is not strictly tissue-specific.</strong>
|
|
Biochim. Biophys. Acta 1264: 238-242, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7495869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7495869</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7495869" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0167-4781(95)00156-b" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="105" class="mim-anchor"></a>
|
|
<a id="Shiang1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shiang, R., Thompson, L. M., Zhu, Y.-Z., Church, D. M., Fielder, T. J., Bocian, M., Winokur, S. T., Wasmuth, J. J.
|
|
<strong>Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.</strong>
|
|
Cell 78: 335-342, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7913883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7913883</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7913883" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(94)90302-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="106" class="mim-anchor"></a>
|
|
<a id="Shimizu2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shimizu, A., Tada, K., Shukunami, C., Hiraki, Y., Kurokawa, T., Magane, N., Kurokawa-Seo, M.
|
|
<strong>A novel alternatively spliced fibroblast growth factor receptor 3 isoform lacking the acid box domain is expressed during chondrogenic differentiation of ATDC5 cells.</strong>
|
|
J. Biol. Chem. 276: 11031-11040, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11134040/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11134040</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11134040" 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.M003535200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="107" class="mim-anchor"></a>
|
|
<a id="Shimizu2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shimizu, A., Takashima, Y., Kurokawa-Seo, M.
|
|
<strong>FGFR3 isoforms have distinct functions in the regulation of growth and cell morphology.</strong>
|
|
Biochem. Biophys. Res. Commun. 290: 113-120, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11779141/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11779141</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11779141" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/bbrc.2001.6190" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="108" class="mim-anchor"></a>
|
|
<a id="Sibley2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sibley, K., Cuthbert-Heavens, D., Knowles, M. A.
|
|
<strong>Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell carcinoma.</strong>
|
|
Oncogene 20: 686-691, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11314002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11314002</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11314002" 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/sj.onc.1204110" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="109" class="mim-anchor"></a>
|
|
<a id="Singh2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Singh, D., Chan, J. M., Zoppoli, P., Niola, F., Sullivan, R., Castano, A., Liu, E. M., Reichel, J., Porrati, P., Pellegatta, S., Qiu, K., Gao, Z., and 12 others.
|
|
<strong>Transforming fusions of FGFR and TACC genes in human glioblastoma.</strong>
|
|
Science 337: 1231-1235, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22837387/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22837387</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22837387[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=22837387" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1220834" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="110" class="mim-anchor"></a>
|
|
<a id="Sobetzko2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sobetzko, D., Braga, S., Rudeberg, A., Superti-Furga, A.
|
|
<strong>Achondroplasia with the FGFR3 1138g-a (G380R) mutation in two sibs sharing a 4p haplotype derived from their unaffected father. (Letter)</strong>
|
|
J. Med. Genet. 37: 958-959, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11186940/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11186940</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11186940" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.37.12.958" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="111" class="mim-anchor"></a>
|
|
<a id="Spranger1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Spranger, J.
|
|
<strong>Bone dysplasia 'families'.</strong>
|
|
Path. Immunopath. Res. 7: 76-80, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3222210/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3222210</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3222210" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1159/000157098" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="112" class="mim-anchor"></a>
|
|
<a id="Su2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Su, N., Sun, Q., Li, C., Lu, X., Qi, H., Chen, S., Yang, J., Du, X., Zhao, L., He, Q., Jin, M., Shen, Y., Chen, D., Chen, L.
|
|
<strong>Gain-of-function mutation in FGFR3 in mice leads to decreased bone mass by affecting both osteoblastogenesis and osteoclastogenesis.</strong>
|
|
Hum. Molec. Genet. 19: 1199-1210, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20053668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20053668</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20053668[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=20053668" 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/ddp590" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="113" class="mim-anchor"></a>
|
|
<a id="Su1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Su, W.-C. S., Kitagawa, M., Xue, N., Xie, B., Garofalo, S., Cho, J., Deng, C., Horton, W. A., Fu, X.-Y.
|
|
<strong>Activation of Stat1 by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism.</strong>
|
|
Nature 386: 288-292, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9069288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9069288</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9069288" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/386288a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="114" class="mim-anchor"></a>
|
|
<a id="Su2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Su, Y.-N., Lee, C.-N., Chien, S.-C., Hung, C.-C., Chien, Y.-H., Chen, C.-A.
|
|
<strong>Rapid detection of FGFR3 gene mutation in achondroplasia by DHPLC system-coupling heteroduplex and fluorescence-enhanced primer-extension analysis.</strong>
|
|
J. Hum. Genet. 49: 399-403, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15221641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15221641</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15221641" 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/s10038-004-0165-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="115" class="mim-anchor"></a>
|
|
<a id="Superti-Furga1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Superti-Furga, A., Eich, G., Bucher, H. U., Wisser, J., Giedion, A., Gitzelmann, R., Steinmann, B.
|
|
<strong>A glycine 375-to-cysteine substitution in the transmembrane domain of the fibroblast growth factor receptor-3 in a newborn with achondroplasia.</strong>
|
|
Europ. J. Pediat. 154: 215-219, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7758520/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7758520</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7758520" 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/BF01954274" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="116" class="mim-anchor"></a>
|
|
<a id="Szabo1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Szabo, J., Bellus, G. A., Kaitila, I., Francomano, C. A.
|
|
<strong>Fibroblast growth factor receptor 3 (FGFR3) mutations in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 59 (suppl.): A287 only, 1996.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="117" class="mim-anchor"></a>
|
|
<a id="Talebi2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Talebi, F., Ghanbari Mardasi, F., Mohammadi Asl, J., Bavarsad, A. H., Tizno, S.
|
|
<strong>Identification of a novel missence (sic) mutation in FGFR3 gene in an Iranian family with LADD syndrome by next-generation sequencing.</strong>
|
|
Int. J. Pediat. Otorhinolaryng. 97: 192-196, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28483234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28483234</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28483234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ijporl.2017.04.016" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="118" class="mim-anchor"></a>
|
|
<a id="Tavormina1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tavormina, P. L., Bellus, G. A., Webster, M. K., Bamshad, M. J., Fraley, A. E., McIntosh, I., Szabo, J., Jiang, W., Jabs, E. W., Wilcox, W. R., Wasmuth, J. J., Donoghue, D. J., Thompson, L. M., Francomano, C. A.
|
|
<strong>A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a lys650-to-met mutation in the fibroblast growth factor receptor 3 gene.</strong>
|
|
Am. J. Hum. Genet. 64: 722-731, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10053006/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10053006</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10053006" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302275" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="119" class="mim-anchor"></a>
|
|
<a id="Tavormina1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tavormina, P. L., Rimoin, D. L., Cohn, D. H., Zhu, Y.-Z., Shiang, R., Wasmuth, J. J.
|
|
<strong>Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type I.</strong>
|
|
Hum. Molec. Genet. 4: 2175-2177, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8589699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8589699</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8589699" 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/4.11.2175" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="120" class="mim-anchor"></a>
|
|
<a id="Tavormina1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tavormina, P. L., Shiang, R., Thompson, L. M., Zhu, Y.-Z., Wilkin, D. J., Lachman, R. S., Wilcox, W. R., Rimoin, D. L., Cohn, D. H., Wasmuth, J. J.
|
|
<strong>Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3.</strong>
|
|
Nature Genet. 9: 321-328, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7773297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7773297</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7773297" 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/ng0395-321" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="121" class="mim-anchor"></a>
|
|
<a id="Thauvin-Robinet2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thauvin-Robinet, C., Faivre, L., Lewin, P., De Monleon, J.-V., Francois, C., Huet, F., Couailler, J.-F., Campos-Xavier, A. B., Bonaventure, J., Le Merrer, M.
|
|
<strong>Hypochondroplasia and stature within normal limits: another family with an asn540-to-ser mutation in the fibroblast growth factor receptor 3 gene. (Letter)</strong>
|
|
Am. J. Med. Genet. 119A: 81-84, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12707965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12707965</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12707965" 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.10238" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="122" class="mim-anchor"></a>
|
|
<a id="Thompson1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thompson, L. M., Plummer, S., Schalling, M., Altherr, M. R., Gusella, J. F., Housman, D. E., Wasmuth, J. J.
|
|
<strong>A gene encoding a fibroblast growth factor receptor isolated from the Huntington disease gene region of human chromosome 4.</strong>
|
|
Genomics 11: 1133-1142, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1664411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1664411</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1664411" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(91)90041-c" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="123" class="mim-anchor"></a>
|
|
<a id="Toydemir2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Toydemir, R. M., Brassington, A. E., Bayrak-Toydemir, P., Krakowiak, P. A., Jorde, L. B., Whitby, F. G., Longo, N., Viskochil, D. H., Carey, J. C., Bamshad, M. J.
|
|
<strong>A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome.</strong>
|
|
Am. J. Hum. Genet. 79: 935-941, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033969</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17033969[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=17033969" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/508433" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="124" class="mim-anchor"></a>
|
|
<a id="Tsai1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tsai, F.-J., Tsai, C.-H., Chang, J.-G., Wu, J.-Y.
|
|
<strong>Mutations in the fibroblast growth factor receptor 3 (FGFR3) cause achondroplasia, hypochondroplasia, and thanatophoric dysplasia: Taiwanese data. (Letter)</strong>
|
|
Am. J. Med. Genet. 86: 300-301, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10482885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10482885</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10482885" 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="125" class="mim-anchor"></a>
|
|
<a id="Tsai1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tsai, F.-J., Wu, J.-Y., Tsai, C.-H., Chang, J.-G.
|
|
<strong>Identification of a common N540K mutation in 8/18 Taiwanese hypochondroplasia patients: further evidence for genetic heterogeneity. (Letter)</strong>
|
|
Clin. Genet. 55: 279-280, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10361991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10361991</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10361991" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1034/j.1399-0004.1999.550412.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="126" class="mim-anchor"></a>
|
|
<a id="Valverde-Franco2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Valverde-Franco, G., Liu, H., Davidson, D., Chai, S., Valderrama-Carvajal, H., Goltzman, D., Ornitz, D. M., Henderson, J. E.
|
|
<strong>Defective bone mineralization and osteopenia in young adult FGFR3 -/- mice.</strong>
|
|
Hum. Molec. Genet. 13: 271-284, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14681299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14681299</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14681299" 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/ddh034" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="127" class="mim-anchor"></a>
|
|
<a id="Van Esch2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Van Esch, H., Fryns, J. P.
|
|
<strong>Acanthosis nigricans in a boy with achondroplasia due to the classical gly380arg mutation in FGFR3.</strong>
|
|
Genet. Counsel. 15: 375-377, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15517832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15517832</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15517832" 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="128" class="mim-anchor"></a>
|
|
<a id="von Gernet1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
von Gernet, S., Schuffenhauer, S., Golla, A., Lichtner, P., Balg, S., Muhlbauer, W., Murken, J., Fairley, J., Meitinger, T.
|
|
<strong>Craniosynostosis suggestive of Saethre-Chotzen syndrome: clinical description of a large kindred and exclusion of candidate regions on 7p.</strong>
|
|
Am. J. Med. Genet. 63: 177-184, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8723106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8723106</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8723106" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1096-8628(19960503)63:1<177::AID-AJMG31>3.0.CO;2-J" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="129" class="mim-anchor"></a>
|
|
<a id="Wang2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, H., Sun, Y., Wu, W., Wei, X., Lan, Z., Xie, J.
|
|
<strong>A novel missense mutation of FGFR3 in a Chinese female and her fetus with hypochondroplasia by next-generation sequencing.</strong>
|
|
Clin. Chim. Acta 423: 62-65, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23726269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23726269</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23726269" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.cca.2013.04.015" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="130" class="mim-anchor"></a>
|
|
<a id="Wilcox1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wilcox, W. R., Tavormina, P. L., Krakow, D., Kitoh, H., Lachman, R. S., Wasmuth, J. J., Thompson, L. M., Rimoin, D. L.
|
|
<strong>Molecular, radiologic, and histopathologic correlations in thanatophoric dysplasia.</strong>
|
|
Am. J. Med. Genet. 78: 274-281, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9677066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9677066</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9677066" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(sici)1096-8628(19980707)78:3<274::aid-ajmg14>3.0.co;2-c" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="131" class="mim-anchor"></a>
|
|
<a id="Wilkie2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wilkie, A. O. M., Bochukova, E. G., Hansen, R. M. S., Taylor, I. B., Rannan-Eliya, S. V., Byren, J. C., Wall, S. A., Ramos, L., Venancio, M., Hurst, J. A., O'Rourke, A. W., Williams, L. J., Seller, A., Lester, T.
|
|
<strong>Clinical dividends from the molecular genetic diagnosis of craniosynostosis.</strong>
|
|
Am. J. Med. Genet. 143A: 1941-1949, 2007. Note: Republication with correction of an article originally published in Am. J. Med. Genet. 140A: 2631-2639, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17621648/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17621648</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17621648" 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.31905" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="132" class="mim-anchor"></a>
|
|
<a id="Wilkie2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wilkie, A. O. M., Byren, J. C., Hurst, J. A., Jayamohan, J., Johnson, D., Knight, S. J. L., Lester, T., Richards, P. G., Twigg, S. R. F., Wall, S. A.
|
|
<strong>Prevalence and complications of single-gene and chromosomal disorders in craniosynostosis.</strong>
|
|
Pediatrics 126: e391-e400, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20643727/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20643727</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20643727[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=20643727" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1542/peds.2009-3491" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="133" class="mim-anchor"></a>
|
|
<a id="Wilkie1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wilkie, A. O. M.
|
|
<strong>Craniosynostosis: genes and mechanisms.</strong>
|
|
Hum. Molec. Genet. 6: 1647-1656, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9300656/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9300656</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9300656" 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/6.10.1647" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="134" class="mim-anchor"></a>
|
|
<a id="Wyrobek2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wyrobek, A. J., Eskenazi, B., Young, S., Arnheim, N., Tiemann-Boege, I., Jabs, E. W., Glaser, R. L., Pearson, F. S., Evenson, D.
|
|
<strong>Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 9601-9606, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16766665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16766665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16766665[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=16766665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0506468103" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="135" class="mim-anchor"></a>
|
|
<a id="Yamashita2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yamashita, A., Morioka, M., Kishi, H., Kimura, T., Yahara, Y., Okada, M., Fujita, K., Sawai, H., Ikegawa, S., Tsumaki, N.
|
|
<strong>Statin treatment rescues FGFR3 skeletal dysplasia phenotypes.</strong>
|
|
Nature 513: 507-511, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25231866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25231866</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25231866" 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/nature13775" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="136" class="mim-anchor"></a>
|
|
<a id="Yasoda2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yasoda, A., Komatsu, Y., Chusho, H., Miyazawa, T., Ozasa, A., Miura, M., Kurihara, T., Rogi, T., Tanaka, S., Suda, M., Tamura, N., Ogawa, Y., Nakao, K.
|
|
<strong>Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway.</strong>
|
|
Nature Med. 10: 80-86, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14702637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14702637</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14702637" 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/nm971" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="137" class="mim-anchor"></a>
|
|
<a id="Zankl2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zankl, A., Elakis, G., Susman, R. D., Inglis, G., Gardener, G., Buckley, M. F., Roscioli, T.
|
|
<strong>Prenatal and postnatal presentation of severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) due to the FGFR3 lys650met mutation.</strong>
|
|
Am. J. Med. Genet. 146A: 212-218, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18076102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18076102</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18076102" 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.32085" 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">
|
|
Carol A. Bocchini - updated : 01/07/2023
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Marla J. F. O'Neill - updated : 01/25/2022<br>Ada Hamosh - updated : 09/10/2018<br>Carol A. Bocchini - updated : 06/05/2018<br>Patricia A. Hartz - updated : 6/30/2015<br>Cassandra L. Kniffin - updated : 10/20/2014<br>Ada Hamosh - updated : 10/9/2014<br>Paul J. Converse - updated : 2/7/2014<br>Ada Hamosh - updated : 10/31/2012<br>Patricia A. Hartz - updated : 2/13/2012<br>Cassandra L. Kniffin - updated : 1/4/2012<br>George E. Tiller - updated : 11/14/2011<br>Patricia A. Hartz - updated : 7/22/2011<br>Cassandra L. Kniffin - updated : 11/8/2010<br>George E. Tiller - updated : 3/2/2010<br>Ada Hamosh - updated : 2/16/2010<br>George E. Tiller - updated : 10/23/2009<br>Nara Sobreira - updated : 7/14/2009<br>George E. Tiller - updated : 4/16/2009<br>Cassandra L. Kniffin - updated : 3/4/2009<br>Cassandra L. Kniffin - updated : 1/5/2009<br>Cassandra L. Kniffin - updated : 10/23/2008<br>Cassandra L. Kniffin - updated : 8/22/2008<br>Cassandra L. Kniffin - updated : 7/29/2008<br>George E. Tiller - updated : 6/11/2008<br>Cassandra L. Kniffin - updated : 5/30/2008<br>George E. Tiller - updated : 5/19/2008<br>Marla J. F. O'Neill - updated : 4/30/2008<br>Marla J. F. O'Neill - updated : 4/30/2007<br>Marla J. F. O'Neill - updated : 4/13/2007<br>Cassandra L. Kniffin - updated : 3/23/2007<br>Marla J. F. O'Neill - updated : 3/8/2007<br>Marla J. F. O'Neill - updated : 3/2/2007<br>Victor A. McKusick - updated : 10/10/2006<br>Cassandra L. Kniffin - updated : 7/11/2006<br>Victor A. McKusick - updated : 4/27/2006<br>George E. Tiller - updated : 2/17/2006<br>Cassandra L. Kniffin - updated : 2/8/2006<br>George E. Tiller - updated : 2/7/2006<br>Marla J. F. O'Neill - updated : 4/18/2005<br>Victor A. McKusick - updated : 1/12/2005<br>Victor A. McKusick - updated : 11/29/2004<br>Victor A. McKusick - updated : 9/27/2004<br>Marla J. F. O'Neill - updated : 6/30/2004<br>Victor A. McKusick - updated : 4/9/2004<br>Victor A. McKusick - updated : 1/22/2004<br>Victor A. McKusick - updated : 7/2/2003<br>Victor A. McKusick - updated : 6/27/2003<br>Victor A. McKusick - updated : 5/15/2003<br>Victor A. McKusick - updated : 2/12/2003<br>Victor A. McKusick - updated : 9/12/2002<br>Patricia A. Hartz - reorganized : 8/7/2002<br>Patricia A. Hartz - updated : 8/7/2002<br>Victor A. McKusick - updated : 2/26/2002<br>Sonja A. Rasmussen - updated : 12/6/2001<br>Victor A. McKusick - updated : 12/4/2001<br>George E. Tiller - updated : 11/7/2001<br>Victor A. McKusick - updated : 10/11/2001<br>Victor A. McKusick - updated : 7/30/2001<br>Victor A. McKusick - updated : 6/26/2001<br>George E. Tiller - updated : 5/17/2001<br>Victor A. McKusick - updated : 4/9/2001<br>Victor A. McKusick - updated : 2/2/2001<br>Michael J. Wright - updated : 1/11/2001<br>Victor A. McKusick - updated : 12/13/2000<br>George E. Tiller - updated : 9/15/2000<br>Victor A. McKusick - updated : 3/15/2000<br>Victor A. McKusick - updated : 1/12/2000<br>Victor A. McKusick - updated : 12/20/1999<br>Victor A. McKusick - updated : 10/21/1999<br>Ada Hamosh - updated : 9/21/1999<br>Victor A. McKusick - updated : 6/29/1999<br>Victor A. McKusick - updated : 6/17/1999<br>Victor A. McKusick - updated : 5/11/1999<br>Victor A. McKusick - updated : 4/21/1999<br>Victor A. McKusick - updated : 4/14/1999<br>Victor A. McKusick - updated : 3/12/1999<br>Victor A. McKusick - updated : 3/9/1999<br>Victor A. McKusick - updated : 2/19/1999<br>Michael J. Wright - updated : 2/12/1999<br>Victor A. McKusick - updated : 1/26/1999<br>Victor A. McKusick - updated : 1/23/1999<br>Victor A. McKusick - updated : 1/13/1999<br>Victor A. McKusick - updated : 1/5/1999<br>Victor A. McKusick - updated : 12/30/1998<br>Victor A. McKusick - updated : 9/2/1998<br>Victor A. McKusick - updated : 8/26/1998<br>Victor A. McKusick - updated : 8/17/1998<br>Victor A. McKusick - updated : 7/27/1998<br>Victor A. McKusick - updated : 7/15/1998<br>Victor A. McKusick - updated : 7/1/1998<br>Victor A. McKusick - updated : 6/23/1998<br>Victor A. McKusick - updated : 6/12/1998<br>Rebekah S. Rasooly - updated : 5/7/1998<br>Victor A. McKusick - updated : 3/2/1998<br>Victor A. McKusick - updated : 2/11/1998<br>Victor A. McKusick - updated : 1/12/1998<br>Victor A. McKusick - updated : 7/3/1997<br>Victor A. McKusick - updated : 5/28/1997<br>Victor A. McKusick - updated : 3/12/1997<br>Moyra Smith - updated : 5/6/1996<br>Moyra Smith - edited : 5/2/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 7/9/1991
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 12/20/2023
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 01/10/2023<br>carol : 01/09/2023<br>carol : 01/07/2023<br>carol : 11/02/2022<br>carol : 11/01/2022<br>carol : 01/25/2022<br>carol : 06/11/2019<br>alopez : 09/10/2018<br>carol : 06/06/2018<br>carol : 06/05/2018<br>carol : 10/20/2017<br>carol : 10/19/2017<br>carol : 10/18/2017<br>joanna : 07/20/2016<br>joanna : 07/19/2016<br>joanna : 07/19/2016<br>joanna : 06/30/2016<br>carol : 4/26/2016<br>mgross : 8/26/2015<br>carol : 7/24/2015<br>mcolton : 6/30/2015<br>carol : 10/21/2014<br>ckniffin : 10/20/2014<br>alopez : 10/9/2014<br>carol : 9/22/2014<br>carol : 7/28/2014<br>carol : 2/21/2014<br>carol : 2/11/2014<br>mgross : 2/10/2014<br>mcolton : 2/7/2014<br>mcolton : 2/5/2014<br>mcolton : 2/5/2014<br>terry : 4/1/2013<br>alopez : 11/5/2012<br>terry : 10/31/2012<br>ckniffin : 7/25/2012<br>terry : 6/7/2012<br>carol : 6/5/2012<br>alopez : 4/12/2012<br>mgross : 2/24/2012<br>mgross : 2/24/2012<br>terry : 2/13/2012<br>carol : 2/2/2012<br>joanna : 1/31/2012<br>ckniffin : 1/4/2012<br>ckniffin : 1/4/2012<br>carol : 11/15/2011<br>terry : 11/14/2011<br>mgross : 8/5/2011<br>terry : 7/22/2011<br>carol : 5/23/2011<br>ckniffin : 1/3/2011<br>ckniffin : 12/28/2010<br>carol : 12/2/2010<br>carol : 11/15/2010<br>wwang : 11/12/2010<br>ckniffin : 11/8/2010<br>terry : 11/3/2010<br>terry : 9/8/2010<br>carol : 8/18/2010<br>wwang : 3/2/2010<br>alopez : 3/2/2010<br>terry : 2/16/2010<br>wwang : 11/2/2009<br>terry : 10/23/2009<br>wwang : 9/15/2009<br>carol : 7/14/2009<br>wwang : 4/20/2009<br>alopez : 4/16/2009<br>carol : 4/3/2009<br>wwang : 3/16/2009<br>ckniffin : 3/4/2009<br>wwang : 1/8/2009<br>ckniffin : 1/5/2009<br>wwang : 10/23/2008<br>carol : 9/4/2008<br>ckniffin : 8/22/2008<br>carol : 8/7/2008<br>ckniffin : 7/29/2008<br>wwang : 6/11/2008<br>wwang : 6/5/2008<br>ckniffin : 5/30/2008<br>ckniffin : 5/30/2008<br>wwang : 5/21/2008<br>terry : 5/19/2008<br>wwang : 5/9/2008<br>terry : 4/30/2008<br>wwang : 6/13/2007<br>wwang : 4/30/2007<br>wwang : 4/20/2007<br>terry : 4/13/2007<br>wwang : 4/11/2007<br>ckniffin : 3/23/2007<br>wwang : 3/9/2007<br>wwang : 3/9/2007<br>terry : 3/8/2007<br>wwang : 3/6/2007<br>terry : 3/2/2007<br>carol : 10/10/2006<br>carol : 10/10/2006<br>terry : 10/10/2006<br>wwang : 7/31/2006<br>ckniffin : 7/11/2006<br>alopez : 5/1/2006<br>terry : 4/27/2006<br>wwang : 4/7/2006<br>terry : 4/6/2006<br>wwang : 3/9/2006<br>wwang : 3/7/2006<br>terry : 2/17/2006<br>terry : 2/17/2006<br>wwang : 2/13/2006<br>ckniffin : 2/8/2006<br>wwang : 2/7/2006<br>carol : 4/26/2005<br>wwang : 4/19/2005<br>terry : 4/18/2005<br>wwang : 1/20/2005<br>wwang : 1/19/2005<br>wwang : 1/13/2005<br>terry : 1/12/2005<br>alopez : 11/29/2004<br>terry : 11/29/2004<br>carol : 9/28/2004<br>terry : 9/27/2004<br>carol : 7/1/2004<br>terry : 6/30/2004<br>tkritzer : 4/14/2004<br>terry : 4/9/2004<br>alopez : 1/23/2004<br>terry : 1/22/2004<br>carol : 7/8/2003<br>terry : 7/2/2003<br>terry : 6/27/2003<br>tkritzer : 5/20/2003<br>terry : 5/15/2003<br>carol : 2/27/2003<br>tkritzer : 2/24/2003<br>terry : 2/12/2003<br>carol : 9/19/2002<br>tkritzer : 9/12/2002<br>tkritzer : 9/12/2002<br>mgross : 8/12/2002<br>mgross : 8/7/2002<br>mgross : 8/7/2002<br>mgross : 8/7/2002<br>mgross : 3/6/2002<br>terry : 2/26/2002<br>mcapotos : 12/17/2001<br>mcapotos : 12/17/2001<br>carol : 12/10/2001<br>mcapotos : 12/6/2001<br>mcapotos : 12/4/2001<br>cwells : 11/20/2001<br>cwells : 11/7/2001<br>carol : 11/5/2001<br>mcapotos : 10/31/2001<br>terry : 10/11/2001<br>cwells : 8/10/2001<br>cwells : 8/8/2001<br>cwells : 8/1/2001<br>terry : 7/30/2001<br>mcapotos : 6/29/2001<br>mcapotos : 6/28/2001<br>terry : 6/26/2001<br>cwells : 5/24/2001<br>cwells : 5/17/2001<br>cwells : 5/17/2001<br>mcapotos : 4/11/2001<br>mcapotos : 4/9/2001<br>terry : 4/9/2001<br>mcapotos : 2/13/2001<br>cwells : 2/8/2001<br>terry : 2/2/2001<br>alopez : 1/11/2001<br>mcapotos : 1/9/2001<br>mcapotos : 12/28/2000<br>terry : 12/13/2000<br>alopez : 9/15/2000<br>mcapotos : 4/6/2000<br>mcapotos : 4/6/2000<br>mcapotos : 4/5/2000<br>terry : 3/15/2000<br>mgross : 1/31/2000<br>terry : 1/12/2000<br>carol : 1/5/2000<br>mcapotos : 1/5/2000<br>mcapotos : 12/29/1999<br>terry : 12/20/1999<br>alopez : 10/27/1999<br>carol : 10/25/1999<br>terry : 10/21/1999<br>carol : 9/21/1999<br>carol : 6/29/1999<br>jlewis : 6/23/1999<br>terry : 6/17/1999<br>mgross : 5/17/1999<br>mgross : 5/13/1999<br>terry : 5/11/1999<br>carol : 4/23/1999<br>terry : 4/21/1999<br>mgross : 4/20/1999<br>mgross : 4/19/1999<br>terry : 4/14/1999<br>mgross : 3/17/1999<br>carol : 3/16/1999<br>terry : 3/12/1999<br>terry : 3/9/1999<br>mgross : 3/3/1999<br>mgross : 3/1/1999<br>mgross : 3/1/1999<br>mgross : 2/24/1999<br>mgross : 2/19/1999<br>terry : 2/12/1999<br>terry : 2/12/1999<br>carol : 1/26/1999<br>carol : 1/23/1999<br>carol : 1/13/1999<br>terry : 1/13/1999<br>carol : 1/6/1999<br>terry : 1/5/1999<br>carol : 1/4/1999<br>terry : 12/30/1998<br>carol : 9/8/1998<br>alopez : 9/2/1998<br>carol : 8/27/1998<br>terry : 8/26/1998<br>carol : 8/18/1998<br>terry : 8/17/1998<br>terry : 7/27/1998<br>carol : 7/23/1998<br>carol : 7/16/1998<br>carol : 7/15/1998<br>carol : 7/14/1998<br>dholmes : 7/13/1998<br>terry : 7/1/1998<br>carol : 7/1/1998<br>terry : 6/23/1998<br>carol : 6/12/1998<br>dholmes : 6/12/1998<br>terry : 5/29/1998<br>carol : 5/26/1998<br>psherman : 5/7/1998<br>psherman : 4/15/1998<br>dholmes : 3/9/1998<br>alopez : 3/3/1998<br>alopez : 3/3/1998<br>dholmes : 3/2/1998<br>dholmes : 3/2/1998<br>alopez : 2/11/1998<br>dholmes : 2/10/1998<br>dholmes : 2/6/1998<br>alopez : 1/12/1998<br>dholmes : 1/6/1998<br>alopez : 10/27/1997<br>terry : 10/23/1997<br>alopez : 7/29/1997<br>alopez : 7/29/1997<br>mark : 7/7/1997<br>alopez : 7/7/1997<br>terry : 7/3/1997<br>alopez : 6/26/1997<br>jenny : 6/5/1997<br>terry : 5/28/1997<br>terry : 3/31/1997<br>terry : 3/12/1997<br>terry : 3/6/1997<br>mark : 12/27/1996<br>terry : 12/12/1996<br>terry : 12/4/1996<br>terry : 11/25/1996<br>terry : 11/22/1996<br>mark : 10/8/1996<br>mark : 10/8/1996<br>mark : 10/5/1996<br>terry : 10/2/1996<br>mark : 5/30/1996<br>terry : 5/29/1996<br>carol : 5/16/1996<br>mark : 5/6/1996<br>mark : 5/6/1996<br>mark : 5/6/1996<br>mark : 5/6/1996<br>mark : 5/3/1996<br>mark : 5/2/1996<br>joanna : 4/26/1996<br>carol : 4/16/1996<br>mark : 4/9/1996<br>terry : 4/5/1996<br>mark : 2/26/1996<br>terry : 2/6/1996<br>mark : 1/18/1996<br>terry : 1/16/1996<br>mark : 12/11/1995<br>mark : 12/6/1995<br>mark : 11/17/1995<br>terry : 2/24/1995<br>carol : 1/18/1995<br>jason : 7/28/1994<br>supermim : 3/16/1992<br>carol : 12/5/1991
|
|
</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> 134934
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
FIBROBLAST GROWTH FACTOR RECEPTOR 3; FGFR3
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
FGFR3/TACC3 FUSION GENE, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: FGFR3</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 205468002, 389157002, 389158007, 440350001, 702361006, 720601000, 787407003, 83015004, 86268005;
|
|
|
|
|
|
<strong>ICD10CM:</strong> Q77.4;
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 4p16.3
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 4:1,793,293-1,808,867 </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="14">
|
|
<span class="mim-font">
|
|
4p16.3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Achondroplasia
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
100800
|
|
</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">
|
|
Bladder cancer, somatic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
109800
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
CATSHL syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
610474
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant; Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Cervical cancer, somatic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
603956
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Colorectal cancer, somatic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
114500
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Crouzon syndrome with acanthosis nigricans
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
612247
|
|
</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">
|
|
Hypochondroplasia
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
146000
|
|
</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">
|
|
LADD syndrome 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
620192
|
|
</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">
|
|
Muenke syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
602849
|
|
</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">
|
|
Nevus, epidermal, somatic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
162900
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
SADDAN
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
616482
|
|
</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">
|
|
Spermatocytic seminoma, somatic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
273300
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Thanatophoric dysplasia, type I
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
187600
|
|
</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">
|
|
Thanatophoric dysplasia, type II
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
187601
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Fibroblast growth factors (FGFs; see 131220) are a family of polypeptide growth factors involved in a variety of activities, including mitogenesis, angiogenesis, and wound healing. FGF receptors, such as FGFR3, contain an extracellular domain with either 2 or 3 immunoglobulin (Ig)-like domains, a transmembrane domain, and a cytoplasmic tyrosine kinase domain (summary by Keegan et al., 1991). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By screening a human K562 cell cDNA library for novel tyrosine kinase receptors, Keegan et al. (1991) isolated a cDNA encoding FGFR3, which is highly homologous to previously described FGFRs. The deduced 806-amino acid protein has an N-terminal signal sequence, followed by 3 extracellular Ig-like domains, a transmembrane domain, and a split C-terminal cytoplasmic kinase domain. The kinase domain contains a GxGxxG motif and a conserved lysine, both of which are characteristic of ATP-binding motifs, and a DFGLAR motif conserved in tyrosine kinases. Northern blot analysis of K562 cells revealed a major transcript of 4.5 kb and a minor transcript of 7.0 kb. Expression of FGFR3 cDNA in COS cells directed formation of a 125-kD glycoprotein. </p><p>Thompson et al. (1991) isolated the FGFR3 gene from the Huntington disease (HD; 143100) region on chromosome 4p16.3. Histochemical analysis using in situ hybridization showed that the FGFR3 gene was expressed in many areas of brain, including caudate and putamen. </p><p>Perez-Castro et al. (1997) reported that the human and mouse FGFR3 amino acid sequences share 92% homology. </p><p>Scotet and Houssaint (1995) identified splice variants of FGFR3 that use 2 alternative exons, 3b and 3c, encoding the C-terminal half of Ig domain 3. They found that epithelial cells show exclusively the 3b transcripts, while fibroblastic cells show a mixture of 3b and 3c transcripts. </p><p>Shimizu et al. (2001) identified an Fgfr3 isoform in mouse that lacks the acid box region within the extracellular domain. PCR analysis showed that this variant, which the authors called delta-AB, was expressed in rat rib cartilage chondrocytes and in undifferentiated cultures of mouse chondroprogenitor cells. </p><p>Jang (2002) identified a soluble variant of FGFR3 produced by skipping exons 8, 9, and 10 in a human osteosarcoma cell line. This splicing event leads to the generation of an mRNA encoding an FGFR3 protein in which the C-terminal portion of the Ig-like-3 domain and the transmembrane domain are deleted, while the remainder of the mature molecule is fused in-frame to the C-terminal cytoplasmic kinase domains. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Perez-Castro et al. (1997) reported that the FGFR3 gene contains 19 exons spanning 16.5 kb. The overall structure and organization of the human FGFR3 gene is nearly identical to that of the mouse Fgfr3 gene. The 5-prime flanking region lacks the typical TATA or CAAT boxes. However, several putative binding sites for transcription factors SP1 (189906), AP2 (107580), KROX24 (128990), IgHC.4, and Zeste (see 601674) are present. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Thompson et al. (1991) mapped the FGFR3 gene to the HD region on chromosome 4p16.3. Using an interspecific backcross mapping panel, Avraham et al. (1994) mapped the Fgfr3 gene to mouse chromosome 5 in a region of homology of synteny with human chromosome 4. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Keegan et al. (1991) showed that human acidic and basic fibroblast growth factors activated FGFR3, as measured by calcium-ion efflux assays. </p><p>Shimizu et al. (2001) found that, when stably transfected into a mouse pro-B cell line, mouse Fgfr3 preferentially mediated the mitogenic response to Fgf1 and showed a poor response to Fgf2. In contrast, the delta-AB isoform, which lacks the acid box, mediated a higher mitogenic response to Fgf2. The delta-AB isoform also required lower concentrations of heparin for activity than Fgfr3 did. Shimizu et al. (2002) found that Fgfr3 induced marked rounding of mouse chondroprogenitor cells, an effect that was not observed with the delta-AB isoform. Fgfr3 also induced complete growth arrest, whereas the delta-AB isoform induced only moderate growth inhibition. Biochemical assays indicated that Fgfr3 and delta-AB differed in their ability to utilize Stat1 (600555) pathways and signals involved in cell rounding. </p><p>Jang (2002) found that, when expressed in insect cells, the secreted isoform of FGFR3 bound both FGF1 (131220) and FGF2 (134920), leading to loss of ligand-binding specificity. </p><p>Using a 3-dimensional cell culture model, Davidson et al. (2005) found that mesenchymal cells released from wildtype, but not Fgfr3 -/-, embryonic day-11.5 (E11.5) mouse limb buds condensed to form nodules and expressed molecular markers characteristic of cells of chondrogenic lineage. In low-density culture, both wildtype and Fgfr3 -/- mesenchymal cells differentiated in response to Fgf2, but only wildtype cells differentiated in response to Fgf18 (603726). Davidson et al. (2005) concluded that FGFR3 and FGF18 are required to promote differentiation of prechondrogenic mesenchymal cells to cartilage-producing chondrocytes. </p><p>Matsushita et al. (2009) observed that chondrocyte-specific activation of Fgfr3 in mice induced premature synchondrosis closure and enhanced osteoblast differentiation around synchondroses. FGF signaling in chondrocytes increased bone morphogenetic protein ligand (e.g., BMP7, 112267) mRNA expression and decreased Bmp antagonist (e.g., noggin, 602991) mRNA expression in a MAPK-dependent manner, suggesting a role for Bmp signaling in the increased bone formation. The enhanced bone formation would accelerate the fusion of ossification centers and limit the endochondral bone growth. The authors proposed that spinal canal and foramen magnum stenosis in heterozygous achondroplasia patients may occur through premature synchondrosis closure. If this is the case, then any growth-promoting treatment for these complications of achondroplasia must precede the timing of the synchondrosis closure. </p><p>Ectopic activation of FGFR3 is associated with several cancers, including multiple myeloma (254500). Salazar et al. (2009) identified the PI3K regulatory subunit PIK3R1 (134934) as a novel interactor of FGFR3 by yeast 2-hybrid screen and confirmed an interaction between FGFR3 and PIK3R1 and PIK3R2 (603157) in mammalian cells. The interaction of FGFR3 with PIK3R1 was dependent upon receptor activation. In contrast to the Gab1 (604439)-mediated association of FGFRs with PIK3R1, the FGFR3-PIK3R1 interaction required FGFR3 tyr760, previously identified as a PLC-gamma (PLCG1; 172420)-binding site. Interaction of PIK3R1 with FGFR3 did not require PLC-gamma, suggesting that PIK3R1 interaction was direct and independent of PLC-gamma binding. FGFR3 and PIK3R1/PIK3R2 proteins also interacted in multiple myeloma cell lines, which consistently express PIK3R1 p85 isoforms but not p50 or p55 isoforms, or PIK3R3 (606076). siRNA knockdown of PIK3R2 in multiple myeloma cells caused an increased ERK response to FGF2 stimulation. Salazar et al. (2009) suggested that an endogenous negative regulatory role for the PIK3R-FGFR3 interaction on the Ras/ERK/MAPK pathway may exist in response to FGFR3 activity. </p><p>Botulinum neurotoxin A causes muscle paralysis by entering motor nerve terminals, where it cleaves SNAP25 (600322) and ultimately inhibits acetylcholine release. Jacky et al. (2013) noted that structural analysis of botulinum neurotoxin A had revealed that the heavy chain A domain (Hc/A) is a structural homolog of FGF2. Using pull-down analyses and other studies in mouse, rat, and human cells, Jacky et al. (2013) identified FGFR3 as a binding partner for botulinum neurotoxin A, with Hc/A of botulinum neurotoxin A specifically binding the second and third extracellular loops of FGFR3. Immunofluorescence microscopy demonstrated Fgfr3 expression at rat motor nerve terminals. Jacky et al. (2013) concluded that FGFR3 is a high-affinity receptor for botulinum neurotoxin A, which uses the same regions of FGFR3 as native ligands and induces FGFR3 phosphorylation. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Although there are significant exceptions to this generalization, dominant mutations in the FGFR3 gene affect predominantly bones that develop by endochondral ossification, whereas dominant mutations involving FGFR1 (136350) and FGFR2 (176943) principally cause syndromes that involve bones arising by membranous ossification, e.g., Pfeiffer syndrome (101600), Crouzon syndrome (123500), Apert syndrome (101200), Saethre-Chotzen syndrome (101400), Beare-Stevenson cutis gyrata (123790), and Jackson-Weiss syndrome (123150). The FGFR3 nucleotides mutated in most cases of achondroplasia (ACH; 100800) and Muenke nonsyndromic craniosynostosis (602849) are among the most highly mutable nucleotides in the human genome.</p><p>The various seemingly diverse disorders due to mutations in the FGFR3 gene were recognized on phenotypic grounds by Spranger (1988) to represent a family of skeletal dysplasias. Spranger (1988) suggested that the achondroplasia family is characterized by a continuum of severity ranging from mild (hypochondroplasia, HCH; 146000) and more severe forms (achondroplasia) to lethal neonatal dwarfism (thanatophoric dysplasia, TD; 187600). </p><p>Passos-Bueno et al. (1999) provided an up-to-date listing of the mutations in FGFR1, FGFR2, and FGFR3 associated with distinct clinical entities, including achondroplasia; hypochondroplasia; (HCH; 146000), platyspondylic lethal skeletal dysplasia (see 151210), thanatophoric dysplasia (see 187600 and 187601), Antley-Bixler syndrome (207410), Apert syndrome, Beare-Stevenson syndrome, Crouzon syndrome, Jackson-Weiss syndrome, Pfeiffer syndrome, and Saethre-Chotzen syndrome. </p><p>In a study in Taiwan, Tsai et al. (1999) found that all 28 cases of achondroplasia had the 1138G-A mutation (134934.0001); 6 of 18 cases of hypochondroplasia had the 1620C-A mutation (134934.0010); 4 of 18 had the 1620C-G mutation (134934.0012), and 8 of the 18 had an undetermined mutation; and both of 2 cases of type I thanatophoric dysplasia had the 742C-T mutation (134934.0005). </p><p><strong><em>Achondroplasia and Hypochondroplasia</em></strong></p><p>
|
|
Shiang et al. (1994) studied the FGFR3 gene as a candidate for the site of the mutation in achondroplasia (ACH; 100800), which maps to the same region. DNA studies revealed point mutations in the FGFR3 gene in both ACH heterozygotes and homozygotes. The mutation on 15 of 16 ACH-affected chromosomes was the same: a G-to-A transition at nucleotide 1138 of the cDNA (134934.0001). The mutation on the other ACH-affected chromosome 4 without the G-to-A transition at nucleotide 1138 had a G-to-C transversion at the same position. Both mutations resulted in the substitution of an arginine residue for a glycine at position 380 of the mature protein, which is in the transmembrane domain of FGFR3. Rousseau et al. (1994) confirmed these mutations by DNA analysis of 17 sporadic cases and 6 unrelated familial forms of achondroplasia. In a review of data on unrelated achondroplasts from multiple laboratories, Bellus et al. (1995) found that 150 were heterozygous for the G-to-A transition at nucleotide 1138 leading to the G380R substitution; 3 were heterozygous for the G-to-C transversion at nucleotide 1138 leading to the same G380R substitution (134934.0002). One achondroplasia patient reported by Superti-Furga et al. (1995) had a G-to-T transversion leading to a G375C (134934.0003) amino acid substitution. </p><p>Lanning and Brown (1997) described an improved method for detecting the common 1138G-A mutation (G380R; 134934.0001). The mutation had typically been detected by SfcI digestion of amplified genomic DNA. Lanning and Brown (1997) showed that the SfcI digestion protocol does not consistently distinguish between DNA samples heterozygous and homozygous for the G1138A substitution, and illustrated how the misdiagnosis of a homozygous affected fetus for one carrying only 1 copy of the mutation could occur. The simple nonradioactive technique that they described could reliably and consistently detect the presence of the G1138A mutation in both the heterozygous and the homozygous state. </p><p>Monsonego-Ornan et al. (2000) analyzed the biochemical consequences of the G380R point mutation that leads to achondroplasia. They found that dimerization and activation of the G380R mutant receptor was predominantly ligand dependent. However, they found a delay in the down-regulation of the mutant receptor, and it was resistant to ligand-mediated internalization. Transgenic mice expressing the human G380R mutant receptor demonstrated a markedly expanded area of FGFR3 immunoreactivity within their epiphyseal growth plates, which is compatible with an in vivo defect in receptor down-regulation. </p><p>The epiphyseal growth plates of individuals carrying the G380R substitution in the FGFR3 gene, the most common cause of achondroplasia, are disorganized and hypocellular and show aberrant chondrocyte maturation. To examine the molecular basis of these abnormalities, Henderson et al. (2000) used a chondrocyte cell line, CFK2, to study the effects of the constitutively active FGFR3 with the G380R substitution. Overexpression of FGFR3 had minimal effects on CFK2 proliferation and maturation compared with the severe growth retardation found in cells expressing the mutant form. Cells expressing the mutant receptor also showed an abnormal apoptotic response to serum deprivation and failed to undergo differentiation under appropriate culture conditions. These changes were associated with altered expression of integrin subunits, which effectively led to a switch in substrate preference of the immature cell from fibronectin to type II collagen. These observations supported those from in vivo studies indicating that FGFR3 mediates an inhibitory influence on chondrocyte proliferation. The authors suggested that the mechanism is related to altered integrin expression. </p><p>Su et al. (2004) introduced denaturing high-performance liquid chromatography (DHPLC) for detection of the 1138G-A mutation, the most common FGFR3 mutation causing achondroplasia. After coupling heteroduplex and fluorescence-enhanced primer-extension analysis, all affected patients with the 1138G-A mutation were successfully identified. </p><p>Cho et al. (2004) presented evidence indicating that activated FGFR3 is targeted for lysosomal degradation by c-Cbl-mediated ubiquitination, and that activating mutations found in patients with achondroplasia and related chondrodysplasias disturb this process, leading to recycling of activated receptors and amplification of FGFR3 signals. They suggested that this mechanism contributes to the molecular pathogenesis of achondroplasia and represents a potential target for therapeutic intervention. The lysosomal targeting defect is additive to other mechanisms proposed to explain the pathogenesis of achondroplasia. </p><p>Leroy et al. (2007) identified the lys650-to-asn mutation (134934.0022) in an 8-year-old girl with mild hypochondroplasia and acanthosis nigricans. </p><p>Heuertz et al. (2006) screened 18 exons of the FGFR3 gene in 25 patients with HCH and 1 with ACH in whom the common mutations G380R and N540K had been excluded. The authors identified 7 novel missense mutations, 1 in the patient with ACH (S279C; 134934.0030) and 6 in patients with HCH (see e.g., Y278C, 134934.0031 and S84L, 134934.0032); no mutations were detected in the remaining 19 patients who were diagnosed clinically with HCH. Heuertz et al. (2006) noted that 4 of the 6 extracellular mutations created additional cysteine residues and were associated with severe phenotypes. Friez and Wilson (2008) agreed with the recommendations of Heuertz et al. (2006) to screen exon 7 of the FGFR3 gene in patients negative for more common variants. </p><p>Almeida et al. (2009) searched for mutations in the FGFR3 gene in 125 Portuguese patients with clinical and radiologic diagnoses of skeletal disorders, including achondroplasia (24), hypochondroplasia (46), Muenke craniosynostosis (52), thanatophoric dysplasia (2), and LADD syndrome (1). A P250R mutation (134934.0014) was identified in 9 (17%) of 52 patients with Muenke craniosynostosis. FGFR3 mutations were found in both cases of thanatophoric dysplasia, and no mutations were identified in the patient with LADD syndrome. Five different mutations were identified in 36 (51%) of 70 patients with achondroplasia or hypochondroplasia; 10 of these diagnoses were reversed based on the molecular findings. The remaining 34 cases of achondroplasia/hypochondroplasia had no FGFR3 sequence changes. Almeida et al. (2009) proposed a molecular strategy to test patients referred with a clinical diagnosis of achondroplasia or hypochondroplasia. </p><p>By microarray-based next-generation sequencing, Wang et al. (2013) identified a G342C mutation (134934.0036) in the extracellular IgIII loop of FGFR3 in a Chinese woman with hypochondroplasia. The mutation was also found in the woman's fetus when ultrasound scan detected an abnormally short femur at 28 weeks' gestation. </p><p><strong><em>Thanatophoric Dysplasia</em></strong></p><p>
|
|
Thanatophoric dysplasia type I and type II (TD1, 187600; TD2, 187601) resembles homozygous achondroplasia in some respects. Tavormina et al. (1995) found mutations in TD type I families that involved the substitution of a cysteine residue for the native amino acid (R248C, 134934.0005; S371C, 134934.0006). In all 16 individuals with type II thanatophoric dysplasia (TD2; 187601), they found a sporadic heterozygous mutation causing a lys650-to-glu change in the FGFR3 tyrosine kinase domain (134934.0004). Tavormina et al. (1995) described another TD1-associated cysteine-generating mutation in the extracellular domain of FGFR3 (S249C; 134934.0013). The authors speculated that the unpaired cysteine residue in this region of the protein might result in formation of intermolecular disulfide bonds between 2 mutant FGFR3 monomers and thereby constitutively activate the receptor complex. </p><p>Rousseau et al. (1996) performed FGFR3 mutation analysis in 26 cases of TD1. Three missense mutations (Y373C, R248C, and S249C) accounted for 73% of the cases. Two stop codon mutations (X807R, 134934.0008; X807C, 134934.0009) and 1 rare G370C mutation (134934.0033) were also found. Rousseau et al. (1996) noted that all reported missense mutations created cysteine residues and were located in the extracellular domain of the receptor. The findings provided support for the hypothesis that the newly created cysteine residues may allow disulfide bonds to form between the extracellular domains of mutant monomers, thus inducing constitutive activation of the homodimer receptor complex. </p><p>Naski et al. (1996) studied the effect of the achondroplasia and thanatophoric dysplasia mutations on the activity and regulation of FGFR3 by transient transfection of NIH3T3 and BaF3 pro-B cells with mutant FGFR3 cDNAs. They showed that each of the mutations studied (R248C, K650E, and G380R) constitutively activates the receptor, as evidenced by ligand-independent receptor tyrosine phosphorylation and cell proliferation. Moreover, the mutations responsible for TD (R248C and K650E) were more strongly activating than the mutation causing ACH (G380R), providing to Naski et al. (1996) a biochemical explanation for the observation that the phenotype of TD is more severe than that of ACH. </p><p>The San Diego form of skeletal dysplasia (187600) has features similar to those of thanatophoric dysplasia but was thought to be distinguished by the presence of large inclusion bodies in the rough endoplasmic reticulum (rER) within chondrocytes. Brodie et al. (1999) found that all 17 cases of the San Diego type of skeletal dysplasia were heterozygous for the same FGFR3 mutations found in TD1, e.g., R248C (134934.0005) present in 7 of 17 cases, S249C (134934.0013) present in 2 of 17 cases, and Y373C (134934.0016) present in 6 of 17 cases. No mutations were identified in cases of the so-called Torrance or Luton types of skeletal dysplasia (151210). </p><p>Observations in thanatophoric dysplasia type II and in mice with homozygous disruption of FGFR3 (Deng et al., 1996; Colvin et al., 1996) indicate that FGFR3 may inhibit cell growth in cartilaginous growth plates, and that the disease-associated mutants have a gain-of-function nature. Su et al. (1997) showed that mutant TD2 FGFR3 has a constitutive tyrosine kinase activity that can specifically activate transcription factor STAT1 (600555). Furthermore, expression of TD2 FGFR3 with the lys650-to-glu mutation (134934.0004) induced nuclear translocation of STAT1, expression of the cell cycle inhibitor p21(WAF1/CIP1) (CDKNA1; 116899), and growth arrest of the cell. Thus, TD2 FGFR3 may use STAT1 as a mediator of growth retardation in bone development. Consistent with this, STAT1 activation and increased p21(WAF1/CIP1) expression was found in the cartilage cells from a TD2 fetus, but not in those from a normal fetus. Thus, abnormal STAT activation and p21(WAF1/CIP1) expression by the TD2 mutant receptor may be responsible for this particular form of FGFR3-related bone disease. </p><p>The lys650 codon of FGFR3 is located within a critical region of the tyrosine kinase domain activation loop. Two missense mutations in this codon result in strong constitutive activation of the FGFR3 tyrosine kinase and cause 3 different skeletal dysplasia syndromes: thanatophoric dysplasia type II caused by lys650 to glu (134934.0004) and SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans; 616482) and thanatophoric dysplasia type I, both due to lys650 to met (134934.0015). Other mutations within the FGFR3 tyrosine kinase domain, e.g., 1620C-A or 1620C-G (both resulting in asn540 to lys (134934.0010 and 134934.0012)) cause hypochondroplasia, a relatively common but milder skeletal dysplasia. In 90 individuals with suspected clinical diagnoses of hypochondroplasia who did not have the asn540-to-lys mutations, Bellus et al. (2000) screened for mutations, in FGFR3 exon 15, that would disrupt a unique BbsI restriction site that includes the lys650 codon. They discovered 3 novel mutations involving codon lys650: 1950G-T and 1950G-C (both resulting in lys650 to asn; 134934.0020 and 134934.0021) and 1948A-C (resulting in lys650 to gln; 134934.0022), occurring in 6 individuals from 5 families. The lys650-to-asn and lys650-to-gln mutations resulted in constitutive activation of the FGFR3 tyrosine kinase but to a lesser degree than that observed with the lys650-to-glu and lys650-to-met mutations. </p><p><strong><em>Crouzon Craniosynostosis with Acanthosis Nigricans</em></strong></p><p>
|
|
Meyers et al. (1995) identified an ala391-to-glu mutation (A391E; 134934.0011) in the FGFR3 gene in affected members of 3 unrelated families with a syndrome of Crouzon craniosynostosis with acanthosis nigricans (612247). </p><p><strong><em>Muenke Coronal Craniosynostosis</em></strong></p><p>
|
|
Bellus et al. (1996) described a pro250-to-arg mutation (P250R; 134934.0014) in FGFR3. On the basis of 61 individuals from 20 unrelated families where coronal synostosis (602849) was due to the P250R mutation in the FGFR3 gene, Muenke et al. (1997) defined a new clinical syndrome distinct from previously defined craniosynostosis syndromes, including the Pfeiffer (101600), Crouzon, Jackson-Weiss (123150), and Apert (101200) syndromes. In addition to the skull findings, some patients had abnormalities on radiographs of hands and feet, including thimble-like middle phalanges, coned epiphyses, and carpal and tarsal fusions. Brachydactyly was seen in some cases; none had clinically significant syndactyly or deviation of the great toe to suggest Apert syndrome or Pfeiffer syndrome, respectively. Sensorineural hearing loss was present in some and developmental delay was seen in a minority. While the radiologic findings of hands and feet can be helpful in the recognition of this syndrome, it was not in all cases clearly distinguishable on a clinical basis from other craniosynostosis syndromes. Therefore, Muenke et al. (1997) suggested that all patients with coronal synostosis should be tested for this mutation. We have designated this syndrome caused by the P250R mutation as Muenke syndrome (602849), or Muenke nonsyndromic coronal craniosynostosis. This is in parallel with the usage for Apert syndrome, Pfeiffer syndrome, Crouzon syndrome, Saethre-Chotzen syndrome, etc. The very tight relationship between genotype and phenotype is shared also by achondroplasia, Apert syndrome, and type IIB multiple endocrine neoplasia (MEN2B; 164761.0013). </p><p>In a cohort of 182 Spanish probands with craniosynostosis, Paumard-Hernandez et al. (2015) screened 5 craniosynostosis-associated genes, including FGFR1, FGFR2, FGFR3, TWIST1 (601622), and EFNB1 (300035). The most frequent mutation was the characteristic Muenke syndrome mutation, P250R in FGFR3, which was detected in 24 patients (13.2% of the cohort). The authors noted that this was somewhat lower than the 24% detected in a UK study of craniosynostosis patients by Wilkie et al. (2010). </p><p><strong><em>Lacrimoauriculodentodigital (LADD) Syndrome 2</em></strong></p><p>
|
|
Lacrimoauriculodentodigital (LADD) syndrome-2 (LADD2; 620192) is a multiple congenital anomaly mainly affecting lacrimal glands and ducts, salivary glands and ducts, ears, teeth, and distal limb segments. Using a positional cloning approach, Rohmann et al. (2006) identified a heterozygous missense mutation in the FGFR3 gene in a father and his 2 children with LADD syndrome (D513N; 134934.0028). </p><p>In a 23-year-old proband and his affected mother in a consanguineous Iranian family with LADD syndrome, Talebi et al. (2017) identified heterozygosity for a missense mutation (D628N; 134934.0038) in the FGFR3 gene. The mutation was not identified in the unaffected father or in 400 control chromosomes. By family history, the proband's maternal uncle was also affected. </p><p><strong><em>Camptodactyly, Tall Stature, Scoliosis, and Hearing Loss Syndrome</em></strong></p><p>
|
|
The camptodactyly, tall stature, scoliosis, and hearing loss syndrome (CATSHL syndrome; 610474) maps to chromosome 4p and recapitulates the phenotype of the Fgfr3 knockout mouse (Toydemir et al., 2006). In affected members of a large family with CATSHL syndrome, Toydemir et al. (2006) identified a heterozygous missense mutation in the FGFR3 gene (R621H; 134934.0029) predicted to cause partial loss of protein function. These findings indicated that abnormal FGFR3 signaling can cause human anomalies by promoting as well as inhibiting endochondral bone growth. </p><p>In 2 brothers, born of consanguineous Egyptian parents, with autosomal recessive inheritance of camptodactyly, tall stature, and hearing loss, Makrythanasis et al. (2014) identified a homozygous missense mutation in the FGFR3 gene (T546K; 134934.0037). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant were not performed, but Makrythanasis et al. (2014) postulated a loss-of-function effect. The unaffected parents and an unaffected sister were heterozygous for the mutation, suggesting a differential functional effect of the mutation compared to that of the heterozygous mutation reported by Toydemir et al. (2006) in their family with CATSHL syndrome. </p><p><strong><em>Somatic Mutations in the FGFR3 Gene</em></strong></p><p>
|
|
Among 62 human cases of seborrheic keratosis (182000), Logie et al. (2005) found that 39% of samples harbored somatic activating FGFR3 mutations, identical to those associated with skeletal dysplasia syndromes and bladder and cervical neoplasms (see, e.g., 134934.0005 and 134934.0013). Logie et al. (2005) implicated FGFR3 activation as a major cause of benign epidermal tumors in humans. </p><p>Hafner et al. (2006) analyzed 39 common epidermal nevi (162900) from 33 patients using a multiplex PCR assay covering 11 FGFR3 point mutations and by direct sequencing of exon 19 of the FGFR3 gene. Somatic mutations were identified in 11 patients, 10 of whom had the R248C mutation, and 1 had a double mutation in exon 10 of the FGFR3 gene (134934.0001 and 134934.0033). In 4 patients tested, FGFR3 mutations were not found in adjacent, histologically normal skin. Hafner et al. (2006) concluded that a large proportion of epidermal nevi are caused by mosaicism of activating FGFR3 mutations in the human epidermis secondary to a postzygotic mutation in early embryonic development, and that the R248C mutation appears to be a hotspot for FGFR3 mutations in epidermal nevi. </p><p><strong><em>Other Disease Associations</em></strong></p><p>
|
|
Riley et al. (2007) analyzed 12 genes involved in the fibroblast growth factor signaling pathway in nonsyndromic cleft lip or palate families and identified 7 likely disease-causing mutations in which structural analysis predicted functional impairment in the FGFR1, FGFR2, FGFR3, and FGF8 (600483) genes. Riley et al. (2007) suggested that the FGF signaling pathway may contribute to as much as 3 to 5% of nonsyndromic cleft lip or palate. </p><p><strong><em>Role in Cancer</em></strong></p><p>
|
|
Dysregulation of oncogenes by translocation to the immunoglobulin heavy chain (IgH) locus (147100) on 14q32 is a seminal event in the pathogenesis of B-cell tumors. In multiple myeloma (254500), translocations to the IgH locus occur in 20 to 60% of cases. For most translocations, the partner chromosome is unknown; for the others, a diverse array of chromosomal partners have been identified, with 11q13 (see cyclin D1; 168461) the only chromosome that is frequently involved. Bergsagel et al. (1996) developed a comprehensive Southern blot assay to identify and distinguish different kinds of IgH switch recombination events. Illegitimate switch recombination fragments (defined as containing sequences from only 1 switch region) are potential markers of translocation events into IgH switch regions and were identified in 15 of 21 myeloma cell lines, including 7 of 8 karyotyped lines that had no detectable 14q32 translocation. These translocation breakpoints involved 6 chromosomal loci: 4p16.3; 6; 8q24.13; 11q13.3; 16q23.1; and 21q22.1. Chesi et al. (1997) found the novel, karyotypically silent translocation t(4;14)(p16.3;q32.3) in 5 myeloma cells lines and in at least 3 of 10 primary tumors. The chromosome-4 breakpoints were clustered in a 70-kb region centromeric to FGFR3, which was thought to be the dysregulated oncogene. Two lines and 1 primary tumor with this translocation selectively expressed an FGFR3 allele containing activating mutations identified previously in thanatophoric dwarfism: tyr373 to cys (134934.0016), lys650 to glu (134934.0004), and lys650 to met (134934.0015). For K650E, the constitutive activation of FGFR3 in the absence of ligand had been proved by transfection experiments. Chesi et al. (1997) proposed that after the t(4;14) translocation, somatic mutation during tumor progression frequently generates an FGFR3 protein that is active in the absence of ligand. Although they could not exclude the possibility that other genes are dysregulated by the translocation t(4;14), several findings pointed to FGFR3. FGFR3 is located no more than 100 kb from the most centromeric breakpoint at 4p16.3, and is on the derivative(14) chromosome that contains the 3-prime IgH enhancer. This is similar to the situation for cyclin D1, which is located 100 to 400 kb from the breakpoint in the translocation t(11;14) that occurs in mantle-cell lymphoma and multiple myeloma tumors. FGFR3 is another example of a gene that can function both as an oncogene and a 'teratogene.' </p><p>Rasmussen et al. (2002) cited a frequency of 3 to 24% for the t(4;14) translocation in multiple myeloma. The translocation was observed at a significantly lower frequency in patients with monoclonal gammopathy of undetermined significance (MGUS), suggesting a role in the transition from MGUS to multiple myeloma. The t(4;14) translocation affects 2 potential oncogenes: FGFR3 and MMSET (602952). Rasmussen et al. (2002) investigated the frequency of FGFR3 dysregulation and its prognostic value in multiple myeloma. In 16 of 110 (14.5%) multiple myeloma bone marrow samples, they found dysregulated FGFR3 expression. Follow-up of 76 multiple myeloma patients showed no significant difference between FGFR3 dysfunction and survival, and no correlation with prognostic factors. Further, no linear relation was observed between FGFR3 and MMSET levels. </p><p>Cappellen et al. (1999) presented evidence indicating an oncogenic role for FGFR3 in carcinomas. They found expression of a constitutively activated FGFR3 in a large proportion of 2 common epithelial cancers, bladder (109800) and cervix (603956). FGFR3 appeared to be the most frequently mutated oncogene in bladder cancer, being mutated in more than 30% of cases. FGFR3 seems to mediate opposite signals, acting as a negative regulator of growth in bone and as an oncogene in several tumor types. All FGFR3 missense somatic mutations identified in these cancers were identical to the germinal activating mutations that cause thanatophoric dysplasia (the authors noted that in 2 mutations, this equivalency occurred because the FGFR3b isoform expressed in epithelial cells contains 2 more amino acids than the FGFR3c isoform expressed in bone). Of the FGFR3 alterations in epithelial tumors, the S249C mutation was the most common, affecting 5 of 9 bladder cancers and 3 of 3 cervical cancers. </p><p>Bladder cancer is the fourth most common cancer in males in the U.S. and the U.K. (Sibley et al., 2001). A region of nonrandom LOH in transitional cell carcinoma of the bladder, 4p16.3, suggests the presence of a tumor suppressor gene. Sibley et al. (2001) investigated the frequency and nature of FGFR3 mutations in a panel of transitional cell carcinomas and cell lines and studied the possible link between mutation and loss of heterozygosity in 4p16.3. Of 63 tumors studied, 31 had previously been assessed to have LOH at 4p16.3. Twenty-six of the 63 tumors (41%) and 4 of the 18 cell lines (22%) had missense mutations in FGFR3. All mutations detected in the panel were found in the germline, and all but one caused lethal conditions. One tumor contained K650Q (134934.0022), which had been identified in less severe cases of skeletal dysplasia. Tumors with and without LOH at 4p16.3 had mutations in FGFR3, suggesting that these 2 events are not causally linked. </p><p>By SSCP and sequencing, Karoui et al. (2001) analyzed the prevalence of FGFR3 mutations in 116 primary tumors of various types (upper aerodigestive tract, esophagus, stomach, lung, and skin). The regions analyzed encompassed all FGFR3 point mutations previously described in severe skeletal dysplasia and cancers. No mutations were detected in the tumor types examined, suggesting that FGFR3 mutations are restricted to a few tumor types, the evidence to date suggesting that they are very specific to bladder carcinomas. </p><p>Kimura et al. (2001) investigated the oncogenic role of mutations in the FGFR3 gene that had been identified in patients with thanatophoric dysplasia. They screened specimens of transitional cell carcinoma of the urinary bladder from 81 patients for TD-causing FGFR3 mutations. Point mutations were detected in 25 of 81 carcinomas. The incidence of TD mutations was significantly higher in low-grade or superficial tumors than in high-grade or muscle-invasive tumors. These findings indicated that TD mutations in the FGFR3 gene do not cause disease progression of bladder carcinoma. </p><p>Goriely et al. (2009) screened 30 spermatocytic seminomas (see 273300) for oncogenic mutations in 17 genes and identified 2 mutations in FGFR3 (both K650E, 134934.0004, which causes thanatophoric dysplasia in the germline) and 5 mutations in HRAS (190020). Massively parallel sequencing of sperm DNA showed that levels of the FGFR3 mutation increase with paternal age and that the mutation spectrum at the lys650 codon is similar to that observed in bladder cancer. Most spermatocytic seminomas showed increased immunoreactivity for FGFR3 and/or HRAS. Goriely et al. (2009) proposed that the paternal age effect mutations activate a common 'selfish' pathway supporting proliferation in the testis, leading to diverse phenotypes in the next generation including fetal lethality, congenital syndromes, and cancer predisposition. </p><p>Singh et al. (2012) reported that a small subset of glioblastoma multiforme tumors (GBMs; 137800) (3.1%; 3 of 97 tumors examined) harbors oncogenic chromosomal translocations that fuse in-frame the tyrosine kinase coding domains of fibroblast growth factor receptor (FGFR) genes FGFR1 (136350) or FGFR3 to the transforming acidic coiled-coil (TACC) coding domains of TACC1 (605301) or TACC3 (605303), respectively. The FGFR-TACC fusion protein displayed oncogenic activity when introduced into astrocytes or stereotactically transduced in the mouse brain. The fusion protein, which localizes to mitotic spindle poles, has constitutive kinase activity and induces mitotic and chromosomal segregation defects and triggers aneuploidy. Inhibition of FGFR kinase corrected the aneuploidy, and oral administration of an FGFR inhibitor prolonged survival of mice harboring intracranial FGFR3-TACC3-initiated glioma. Singh et al. (2012) concluded that FGFR-TACC fusions could potentially identify a subset of GBM patients who would benefit from targeted FGFR kinase inhibition. </p><p>Frattini et al. (2018) demonstrated that human tumors with FGFR3-TACC3 fusions cluster within transcriptional subgroups that are characterized by the activation of mitochondrial functions. FGFR3-TACC3 activates oxidative phosphorylation and mitochondrial biogenesis and induces sensitivity to inhibitors of oxidative metabolism. Phosphorylation of the phosphopeptide PIN4 (300252) is an intermediate step in the signaling pathway of the activation of mitochondrial metabolism. The FGFR3-TACC3-PIN4 axis triggers the biogenesis of peroxisomes and the synthesis of new proteins. The anabolic response converges on the PGC1-alpha (604517) coactivator through the production of intracellular reactive oxygen species, which enables mitochondrial respiration and tumor growth. Frattini et al. (2018) concluded that their data illustrated the oncogenic circuit engaged by FGFR3-TACC3 and showed that FGFR3-TACC3-positive tumors rely on mitochondrial respiration, highlighting this pathway as a therapeutic opportunity for the treatment of tumors with FGFR3-TACC3 fusions. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Colvin et al. (1996) reported the findings in mice homozygous for a targeted disruption of Fgfr3. Skeletal defects included kyphosis, scoliosis, crooked tails, and curvature and overgrowth of long bones and vertebrae. Contrasts between the skeletal phenotype of the mice and achondroplasia suggested to the authors that activation of FGFR3 may cause achondroplasia. Furthermore, the mice showed defects of the inner ear, including failure of pillar cell differentiation and tunnel of Corti formation, resulting in profound deafness. The results demonstrated that Fgfr3 is essential for normal endochondral ossification and inner ear development. </p><p>Deng et al. (1996) reported studies in mice made FGFR3 deficient by targeted disruption in the Fgfr3 gene by homologous recombination. Fgfr3 +/- mice showed no phenotypic abnormalities. Fgfr -/- mice had phenotypic effects restricted to bones that arise by endochondral ossification, i.e., increased length of the vertebral column and long bones occurred. Histologic studies revealed cellular expansion, involving hypertrophic chondrocytes, in the growth plates of vertebrae and long bones of mutant homozygotes. Deng et al. (1996) proposed that the function of FGFR3 is to limit osteogenesis. They noted that the recessive loss-of-function mutation in Fgfr3 -/- mice produces a phenotype that is the opposite of that observed in achondroplasia and thanatophoric dwarfism. They proposed that the FGFR3 mutations in these disorders lead to constitutive activation (ligand independent activation) of the receptor. </p><p>To study the function of FGFR3 in bone growth and to create animal models for the FGFR3-related inherited skeletal disorders, Li et al. (1999) introduced a lys644-to-glu (K644E) point mutation, which corresponded to the lys650-to-glu mutation (K650E; 134934.0004) found in TD2 patients, into the murine Fgfr3 gene using a knockin approach. They found that in mice the lys644-to-glu mutation resulted in retarded endochondral bone growth with its severity directly linked to the expression level of the mutated Fgfr3. Mice heterozygous for the mutation expressed the mutant allele at approximately 20% of the wildtype level and exhibited a mild bone dysplasia. However, when the copy number of the mutant increased from 1 to 2 (homozygosity), the retardation of bone growth became more severe and showed phenotypes resembling those of achondroplasia patients, characterized by dramatically reduced proliferation of growth plate cartilage, macrocephaly, and shortening of the long bones, which was most pronounced in the femur. Molecular analysis showed that expression of the mutant receptor caused the activation of Stat1 (600555), Stat5a (601511), and Stat5b, and the upregulation of p16 (600160), p18 (603369), and p19 (600927) cell cycle inhibitors, leading to dramatic expansion of the resting zone of chondrocytes at the expense of the proliferating chondrocytes. The findings provided direct genetic evidence that point mutations in FGFR3 cause human skeletal dysplasias and uncovered a mechanism through which the FGFR3 signals regulate bone growth. </p><p>Iwata et al. (2000) generated a mouse model with the Fgfr3 K644E mutation, which in humans results in thanatophoric dysplasia type II (TD2). Long-bone abnormalities were identified as early as E14, during initiation of endochondral ossification. Increased expression of Patched (601309) was observed, independent of unaltered expression of parathyroid hormone-related peptide receptor (168468) and Indian Hedgehog (Ihh; 600726), suggesting a new regulatory role for Fgfr3 in embryos. The mutation enhanced chondrocyte proliferation during early embryonic skeletal development, in contrast to previous reports that showed decreased proliferation in postnatal-onset dwarf mice with activating Fgfr3 mutations. Additionally, suppressed chondrocyte differentiation was observed throughout the embryonic stages, suggesting that decreased differentiation is the primary cause of retarded longitudinal bone growth in TDII. The authors hypothesized that signaling through Fgfr3 both promotes and inhibits chondrocyte proliferation, depending on the time during development. </p><p>Chen et al. (2001) engineered a transgenic mouse with a ser365-to-cys substitution in Fgfr3, which is equivalent to a human mutation causing thanatophoric dysplasia type I (S371C; 134934.0006). The mutant mice exhibited shortened limbs as a result of markedly reduced proliferation and impaired differentiation of growth plate chondrocytes. The receptor-activating mutation also resulted in downregulation of expression of Ihh and parathyroid hormone-related protein (PTHRP) receptor genes. Interactions between Fgfr3- and PTHRP-receptor-mediated signals during endochondral ossification were examined in cultured embryonic metatarsal bones. Consistent with the in vivo observations, Fgf2 inhibited bone growth in culture and induced downregulation of Ihh and PTHRP receptor gene expression. Furthermore, PTHRP partially reversed the inhibition of long bone growth caused by activation of Fgfr3; however, it impaired the differentiation of chondrocytes in an Fgfr3-independent manner. The authors hypothesized that Fgfr3 and Ihh-PTHRP signals may be transmitted by 2 interacting parallel pathways that mediate both overlapping and distinct functions during endochondral ossification. </p><p>Iwata et al. (2001) introduced the murine equivalent (K644M) of the human SADDAN point mutation (K650M; 134934.0015) into the mouse Fgfr3 gene. Heterozygous mutant mice showed a phenotype similar to human SADDAN, e.g., the majority of the SADDAN mice survived the perinatal period. The long bone abnormalities in SADDAN mice were milder than the TDII model. In addition, overgrowth of the cartilaginous tissues was observed in the rib cartilage, trachea, and nasal septum. Unlike the TDII model, FGF ligands at low concentrations differentially activated Map kinase in primary chondrocyte cultures from wildtype and SADDAN mice. </p><p>To investigate the effect of the Fgfr3 K644E mutation on CNS development, Lin et al. (2003) generated tissue-specific TDII mice by crossing K644E transgenic mice with CNS-specific Nestin-cre (NES; 600915) or cartilage-specific Col2a1-cre (COL2A1; 120140) mice. CNS-specific neonates did not demonstrate a profound skeletal phenotype; however, many pups exhibited round heads. MRI and histochemical analysis illustrated asymmetric changes in cortical thickness and cerebellar abnormalities in these mice, which correlated with brain abnormalities observed in human TDII patients and which were not seen in cartilage-specific mice. Upon examination of the spinal cords of adult CNS-specific mice, premature differentiation of oligodendrocyte progenitors was observed. </p><p>Using a combination of imaging, classic histology and molecular cell biology, Valverde-Franco et al. (2004) showed that young adult Fgfr3 -/- mice are osteopenic due to reduced cortical bone thickness and defective trabecular bone mineralization. The reduction in mineralized bone and lack of trabecular connectivity observed by microcomputed tomography were confirmed in histologic and histomorphometric analyses, which revealed a significant decrease in calcein labeling of mineralizing surfaces and a significant increase in osteoid in the long bones of 4-month-old Fgfr3 -/- mice. These alterations were associated with increased staining for recognized markers of differentiated osteoblasts and increased numbers of tartrate-resistant acid phosphatase-positive osteoclasts. Primary cultures of adherent bone marrow-derived cells from Fgfr3 -/- mice expressed markers of differentiated osteoblasts but developed fewer mineralized nodules than Fgfr3 +/+ cultures of the same age. Valverde-Franco et al. (2004) hypothesized a role for FGFR3 in postnatal bone growth and remodeling, and suggested that it may be a potential therapeutic agent for osteopenic disorders and those associated with defective bone mineralization. </p><p>C-type natriuretic peptide (CNP; 600296) regulates endochondral bone growth through guanylyl cyclase type B. Yasoda et al. (2004) showed that targeted overexpression of CNP in chondrocytes counteracted dwarfism in a mouse model of achondroplasia with activated FGFR3 in cartilage. </p><p>Logie et al. (2005) targeted an activated FGFR3 mutant, S249C (134934.0013), to basal cells of the epidermis of mice. FGFR3-mutant mice developed benign epidermal tumors with no sign of malignancy. These skin lesions had features in common with acanthosis nigricans and other benign human skin tumors, including seborrheic keratosis, one of the most common benign epidermal tumors in humans. </p><p>Using PC12 cell lines stably expressing inducible mutant receptors containing the TDII mutation, K650E (134934.0004), Nowroozi et al. (2005) observed sustained activation of Erk1/2 (see 601795) and activation of Stat1 and Stat3 (102582), but not Stat5a (601511), in the absence of ligand. This activation led to neurite outgrowth, a phenotypic readout of constitutive receptor activity; sustained Erk1/2 activity was required for this ligand-independent differentiation. Silencing of Stat1 or Stat3 independently or in combination had no significant effect on ligand-independent neurite outgrowth, Erk1/2 activation, or p21 (CDKN1A; 116899) protein levels. Nowroozi et al. (2005) proposed a model in which sustained activation of ERK1/2 is a key regulator of the increased transition to hypertrophic differentiation of the growth plate, whereas activation of STAT1 and STAT3 is not required. </p><p>Eswarakumar and Schlessinger (2007) generated mice with selective inactivation of the Fgfr3b and Fgfr3c isoforms, respectively. Fgfr3c-null mice showed dramatic overgrowth of the axial and appendicular skeleton and other abnormalities resulting from strong stimulation of chondrocyte proliferation in the growth plates. These mice also showed decreased bone mineral density. In contrast, Fgfr3b-null mice showed no apparent phenotype and had bone mineral density similar to wildtype mice. The findings demonstrated that the mesenchymal Fgfr3c isoform is responsible for controlling chondrocyte proliferation and differentiation in skeletal development. </p><p>Mansour et al. (2009) generated mice homozygous and heterozygous for a P244R mutation in the Fgfr3 gene, which is the equivalent of the human P250R mutation, as a mouse model of Muenke syndrome (602849). Fgfr3 P244R/+ and P244R/P244R mice showed dominant, fully penetrant low frequency hearing loss that was similar but more severe than in Muenke syndrome patients. Mouse hearing loss correlated with an alteration in the fate of supporting cells (Deiters-to-pillar cells) along the entire length of the cochlear duct, especially at the apical or low frequency end. There was excess outer hair cell development in the apical region. Hearing loss was dosage sensitive as homozygotes were more severely affected than heterozygotes. </p><p>Using microcomputed tomography and histomorphometric analyses, Su et al. (2010) found that 2-month-old Fgfr3(G369C/+) mice (mouse model mimicking human ACH) showed decreased bone mass due to reduced trabecular bone volume and bone mineral density, defect in bone mineralization, and increased osteoclast numbers and activity. Compared with primary cultures of bone marrow stromal cells (BMSCs) from wildtype mice, Fgfr3(G369C/+) cultures showed decreased cell proliferation, increased osteogenic differentiation including upregulation of alkaline phosphatase activity and expression of osteoblast marker genes, and reduced bone matrix mineralization. Su et al. (2010) suggested that decreased cell proliferation and enhanced osteogenic differentiation observed in Fgfr3(G369C/+) BMSCs may be caused by upregulation of p38 (MAPK14; 600289) phosphorylation, and that enhanced Erk1/2 (MAPK3; 601795) activity may be responsible for the impaired bone matrix mineralization. In vitro osteoclast formation and bone resorption assays demonstrated that osteoclast numbers and bone resorption area were increased in cultured bone marrow cells derived from Fgfr3(G369C/+) mice. Su et al. (2010) concluded that gain-of-function mutations in FGFR3 may lead to decreased bone mass by regulating both osteoblast and osteoclast activities. </p><p>Yamashita et al. (2014) showed that statin treatment could rescue patient-specific induced pluripotent stem cells (iPSCs) and the chondrodysplasia phenotype of Fgfr3(Ach) transgenic mice that expressed an activated FGFR3 containing the G380R mutation (134934.0001) in the growth plate (Naski et al., 1998). Yamashita et al. (2014) converted fibroblasts from patients with thanatophoric dysplasia type I (TD1; 187600) and achondroplasia into iPSCs. The chondrogenic differentiation of TD1 iPSCs and achondroplasia iPSCs resulted in the formation of degraded cartilage. Yamashita et al. (2014) found that statins could correct the degraded cartilage in both chondrogenically differentiated TD1 and achondroplasia iPSCs. Treatment of Fgfr3(Ach) model mice with statin led to a significant recovery of bone growth. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>38 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 ACHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
NEVUS, EPIDERMAL, SOMATIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, GLY380ARG, 1138G-A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28931614,
|
|
|
|
|
|
gnomAD: rs28931614,
|
|
|
|
|
|
ClinVar: RCV000017724, RCV000017763, RCV000029207, RCV000255750, RCV000763121, RCV001266979, RCV001807732, RCV002276551, RCV003227605, RCV004545731, RCV004783725, RCV004798732
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In achondroplasia (ACH; 100800), codon 380 in the FGFR3 gene is changed from GGG to AGG or CGG (Shiang et al., 1994). Codon 379 is TAC (tyr). Rousseau et al. (1994) found the gly380-to-arg mutation in all 23 cases of achondroplasia studied (17 sporadic and 6 familial). Twenty-two of the 23 probands had the G-to-A transition; only 1 had the G-to-C transversion (134934.0002). See also Ikegawa et al. (1995). </p><p>Nucleotide 1138 of the FGFR3 gene may be one of the most mutable bases in the human genome. Wilkie (1997) commented that it seems unlikely to be coincidental that the 3 highest germline point mutation rates described in the human (elevated approximately 1000-fold over background) all concern FGFRs: G380R and P250R in FGFR3 (134934.0014) and S252W in FGFR2 (176943.0010). These 3 mutations result in achondroplasia, Muenke nonsyndromic coronal craniosynostosis, and Apert syndrome (101200), respectively. Increased paternal age associated with achondroplasia and Apert syndrome has long been known, and an exclusively paternal origin of mutation was shown in studies of 57 Apert syndrome patients by Moloney et al. (1996) and in 10 achondroplasia patients by Szabo et al. (1996). </p><p>In a 24-year-old woman whose fetus was suspected by ultrasonography to have a short-limb disorder, Saito et al. (2000) made the diagnosis of achondroplasia by identifying the 1138G-A mutation using PCR with specific primers. Restriction fragment length polymorphism analysis of PCR products was done with SfcI. DNA for the studies was extracted from maternal plasma; the mutation was not found in maternal leukocytes. </p><p>Van Esch and Fryns (2004) described acanthosis nigricans in a 9-year-old boy with achondroplasia due to the classic gly380-to-arg mutation in FGFR3. </p><p>Affected sibs with classic achondroplasia but unaffected parents were described by Henderson et al. (2000) and Sobetzko et al. (2000). Both were apparent instances of germinal mosaicism. </p><p>In a sperm study of 97 men aged 22 to 80 years, Wyrobek et al. (2006) found associations between increased age and genomic defects as measured by the DNA fragmentation index and increased age and the FGFR3 1138G-A mutation without evidence for an age threshold. However, there was no association between age and frequency of sperm with immature chromatin, aneuploidies/diploidies, FGFR2 mutations causing Apert syndrome, or sex ratio. </p><p>In 3 sibs who were the product of the first and third pregnancies of healthy nonconsanguineous parents, Natacci et al. (2008) identified heterozygosity for the G380R mutation in the FGFR3 gene. The mutation was not found in lymphocytic DNA from the parents; however, DNA analysis of a sperm sample from the 37-year-old father showed the G380R mutation. The authors stated that this was the second reported case of germinal mosaicism causing recurrent achondroplasia in a subsequent conception. </p><p>He et al. (2010) found that the G380R mutation within the transmembrane domain of FGFR3 increased the phosphorylation of tyr647 and tyr648 within the FGFR3 catalytic domain in the absence of FGF1 and at low FGF1 concentration. They determined that the increased kinase activity of mutant FGFR3 was due to a conformational change. The amino acids that mediate helix-helix contacts in the wildtype dimer are leu377, val381, phe384, and ile387, whereas the mutant dimer interface is rotated to involve ile376, arg380, phe383, ile387, val390, and thr394. The 2 alanines at position 391 face each other directly in the wildtype structure, but are rotated away from each other in the mutant structure. He et al. (2010) hypothesized that the rotation at the dimerization interface would induce a concomitant rotation of the catalytic domains with respect to each other and change their kinetics of kinase activity. </p><p>He et al. (2011) showed that the G380R mutation decreased the probability of heterodimer formation between mutant and wildtype subunits at low ligand concentration, but not at high ligand concentration. </p><p><strong><em>Nevus, Epidermal, Somatic</em></strong></p><p>
|
|
Hafner et al. (2006) analyzed the FGFR3 gene in 39 common epidermal nevi (162900) from 33 patients and identified mosaicism for a double mutation in exon 10 of the FGFR3 gene in 1 patient: the G372C mutation (G370C; 134934.0033) and the G382R mutation. Codons were numbered according to the FGFR3 IIIb isoform. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 ACHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, GLY380ARG, 1138G-C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28931614,
|
|
|
|
|
|
gnomAD: rs28931614,
|
|
|
|
|
|
ClinVar: RCV000017725, RCV000727147, RCV000987394, RCV004532375, RCV004795424
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Rousseau et al. (1994) found the gly380-to-arg mutation in all 23 cases of achondroplasia (ACH; 100800) studied (17 sporadic and 6 familial). Twenty-two of the 23 probands had the G-to-A transition (134934.0001); only 1 had the G-to-C transversion. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 ACHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, GLY375CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs75790268,
|
|
|
|
|
|
|
|
ClinVar: RCV000017727, RCV002228031
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Superti-Furga et al. (1995) found a G375C mutation in a newborn with achondroplasia (ACH; 100800) born to a 26-year-old mother and a 42-year-old father. The amino acid substitution was due to heterozygosity for a de novo G-to-T transversion at the first position of codon 375. Although the phenotype appeared to be characteristic of achondroplasia, the possibility that differences from classic achondroplasia might be evident at a later age was mentioned. It is of note that this was a twin pregnancy, first demonstrated by ultrasound examination at week 32 of gestation. The previously normal-appearing twin suffered intrauterine death at about week 35 and the achondroplastic twin was delivered by cesarean section. </p><p>Ikegawa et al. (1995) also found the gly375-to-cys mutation in a single case. In 7 Japanese patients with achondroplasia, 6 sporadic cases all showed a G-to-A mutation at codon 380 (134934.0001). The single familial case bore a G-to-T transition at codon 375, resulting in substitution of cysteine for glycine; both mother and child were affected. Nishimura et al. (1995) reported the atypical radiologic findings in the patient with the gly375-to-cys mutation. </p><p>Nishimura and Takada (1997) reported yet another patient with achondroplasia due to the gly375-to-cys mutation of the FGFR3 gene. The patient was a Japanese boy born of healthy, unrelated parents: a 38-year-old father and a 33-year-old mother. Short femurs were detected at 35 weeks' gestation. Although mild micromelia was suspected at birth, radiologic examination was not carried out at that time. Subsequently, rhizomelia became evident, and trident hands were noted. Skeletal survey at age 6 months showed narrow thorax, interpediculate narrowing of the lumbar spine, hypoplastic ilia, and short limbs with mild metaphyseal cupping. The skeletal abnormality was considered milder than those in achondroplasia. At age 8 months, his facial appearance was said not to be typical of achondroplasia; he had neither frontal bossing nor overt midface 'recession.'</p><p>Chen et al. (1999) demonstrated that the gly375-to-cys mutation in human FGFR3 causes ligand-independent dimerization and phosphorylation of FGFR3. They also showed that the equivalent substitution at position 369 (gly369 to cys) in mouse Fgfr3 causes dwarfism with features mimicking human achondroplasia. As is the case in humans, homozygous mice were more severely affected than heterozygotes. The resulting mutant mice exhibited macrocephaly and shortened limbs due to retarded endochondral bone growth and premature closure of cranial base synchondroses. Compared with their wildtype littermates, mutant mice growth plates shared an expanded resting zone and narrowed proliferating and hypertrophic zones, which was correlated with the activation of Stat proteins and upregulation of cell cycle inhibitors. Reduced bone density is accompanied by increased activity of osteoclasts and upregulation of genes that are related to osteoblast differentiation, including osteopontin (166490), osteonectin (182120), and osteocalcin (112260). They demonstrated an essential role for FGF/FGFR3 signals in both chondrogenesis and osteogenesis during endochondral ossification. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 THANATOPHORIC DYSPLASIA, TYPE II</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MULTIPLE MYELOMA, SOMATIC, INCLUDED<br />
|
|
SPERMATOCYTIC SEMINOMA, SOMATIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, LYS650GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs78311289,
|
|
|
|
|
|
gnomAD: rs78311289,
|
|
|
|
|
|
ClinVar: RCV000017728, RCV000017729, RCV000017730, RCV000255799, RCV003155029, RCV003234912, RCV003317039, RCV004532376, RCV005031441
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Thanatophoric Dysplasia, Type II</em></strong></p><p>
|
|
In 16 individuals with type II thanatophoric dysplasia (TD2; 187601), Tavormina et al. (1995) identified a heterozygous 1948A-G mutation in the FGFR3 gene, causing a lys650-to-glu (K650E) substitution in the tyrosine kinase domain. </p><p>In a review of 91 cases of TD by Wilcox et al. (1998), the K650E mutation was the only cause of TD type II, and occurred in 17 cases (19%). </p><p>Li et al. (2006) reported a female fetus with TD2 and occipital encephalocele, in whom they identified the K650E mutation in the FGFR3 gene. </p><p>Lievens and Liboi (2003) found that the K605E mutation hampers complete maturation of FGFR3. The mutation causes the immature phosphorylated FGFR3 intermediate glycomers to activate STAT1 (600555) from the endoplasmic reticulum. They suggested that this was the first report of a tyrosine kinase receptor that signals from within the cell in its immature form. </p><p><strong><em>Multiple Myeloma, Somatic</em></strong></p><p>
|
|
Chesi et al. (1997) found this mutation in cell lines and tumors from cases of multiple myeloma. They proposed that after the illegitimate switch recombination between 4p and 14q as the result of the t(4;14) translocation, somatic mutation during tumor progression generated an FGFR3 protein that was active in the absence of ligand. </p><p><strong><em>Spermatocytic Seminoma, Somatic</em></strong></p><p>
|
|
Goriely et al. (2009) screened 30 spermatocytic seminomas (see 273300) for oncogenic mutations in 17 genes and identified the K650E mutation in FGFR3 in 2 tumors. Massively parallel sequencing of sperm DNA showed that levels of the FGFR3 mutation increase with paternal age and that the mutation spectrum at the lys650 codon is similar to that observed in bladder cancer. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MULTIPLE MYELOMA, SOMATIC, INCLUDED<br />
|
|
SKELETAL DYSPLASIA WITH ACANTHOSIS NIGRICANS, INCLUDED<br />
|
|
NEVUS, EPIDERMAL, SOMATIC, INCLUDED<br />
|
|
KERATOSIS, SEBORRHEIC, SOMATIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, ARG248CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913482,
|
|
|
|
|
|
|
|
ClinVar: RCV000017731, RCV000017732, RCV000017733, RCV000017734, RCV000017735, RCV000327823, RCV000414822, RCV000763118, RCV001196297, RCV001526641, RCV001804739, RCV001849270, RCV002243648, RCV002276552, RCV003155030, RCV003332082, RCV003388567, RCV004795425, RCV004798733, RCV005025063
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Thanatophoric Dysplasia, Type I</em></strong></p><p>
|
|
Of 39 individuals with type I thanatophoric dysplasia (TD1; 187600), Tavormina et al. (1995) found an arg248-to-cys mutation resulting from a C-to-T transition at nucleotide 742 in 22 and a ser371-to-cys mutation (134934.0006) in 1. Both of these mutations were in the extracellular region of the FGFR3 protein. </p><p>Although type II thanatophoric dysplasia (187601) cases have been found to have a single recurrent K650E change (134934.0004), type I cases have different mutations affecting either the extracellular or intracellular domains of FGFR3. However, mutations in the FGFR3 gene were identified in only approximately 60% of the type I TD cases. These findings, and the range of symptoms observed, suggested that type I TD is heterogeneous in genetic background. Pokharel et al. (1996) described a Japanese type I TD patient followed for more than 9 years. They found that the patient had the arg248-to-cys mutation as did 4 other Japanese cases of type I TD. No association was found with the ser371-to-cys mutation. </p><p>The R248C mutation was the most frequent cause of thanatophoric dysplasia in the 91 cases reviewed in detail by Wilcox et al. (1998), occurring in almost 50% (45) of the cases. </p><p>Although prenatal diagnosis of TD had been accomplished by ultrasonography in the second trimester, it was not always possible to distinguish between TD and other osteochondrodysplasias in utero. Using restriction enzyme analysis, Sawai et al. (1999) identified the common 742C-T mutation in the FGFR3 gene in a fetus at 27 weeks' gestation. </p><p>Hyland et al. (2003) described a woman who was a somatic and germline mosaic for the R248C missense mutation in FGFR3. She had disproportionate short stature, rhizomelic limb shortening, and other skeletal features accompanied by widespread acanthosis nigricans. These features were clearly different from those seen in thanatophoric dysplasia or other skeletal dysplasias. Her only pregnancy ended in delivery of a fetus with lethal short-limb dwarfism and pulmonary hyperplasia, strongly suggestive of thanatophoric dysplasia. </p><p><strong><em>Nevus, Epidermal, Somatic</em></strong></p><p>
|
|
Hafner et al. (2006) analyzed the FGFR3 gene in 39 common epidermal nevi (162900) from 33 patients and identified the R248C mutation in 10 of 11 mutation-positive patients; In 4 patients tested, FGFR3 mutations were not found in adjacent, histologically normal skin. Hafner et al. (2006) concluded that a large proportion of epidermal nevi are caused by mosaicism of activating FGFR3 mutations in the human epidermis secondary to a postzygotic mutation in early embryonic development, and that the R248C mutation appears to be a hotspot for FGFR3 mutations in epidermal nevi. </p><p>Garcia-Vargas et al. (2008) reported a 5-year-old Mexican girl with epidermal nevi, mental impairment, and seizures in whom they identified somatic mosaicism for a heterozygous R248C mutation in lesional skin and lymphocytes but not in normal skin. She had generalized linear epidermal nevi with a soft, velvety texture following the lines of Blaschko, and sparing the scalp, palms, and soles. She had delayed development, and brain CT showed cortical and subcortical atrophy, a subdural hygroma, and hypoplasia of the corpus callosum. The findings suggested that the mutation involved the skin, brain, and blood cells. Although there were no skeletal anomalies, Garcia-Vargas et al. (2008) considered the phenotype to be consistent with a mosaic manifestation of TD type I, but also proposed a preliminary designation of 'FGFR3 epidermal nevus syndrome.' </p><p><strong><em>Multiple Myeloma, Somatic</em></strong></p><p>
|
|
Intini et al. (2001) investigated FGFR3 mutations in a series of 53 multiple myeloma (254500) cases, 11 of which had a t(4;14) translocation and FGFR3 overexpression. The arg248-to-cys mutation was found in 1 case with t(4;14). Intini et al. (2001) concluded that FGFR3 mutations occur in only a small fraction of multiple myeloma cases with t(4;14). </p><p><strong><em>Keratosis, Seborrheic, Somatic</em></strong></p><p>
|
|
Logie et al. (2005) identified a somatic R248C mutation in the FGFR3 gene in 5 seborrheic keratoses (182000). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, SER371CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913484,
|
|
|
|
|
|
|
|
ClinVar: RCV000017736, RCV000757295, RCV001528646
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 of 39 individuals with thanatophoric dysplasis type I (TD1; 187600), Tavormina et al. (1995) found an A-to-T transversion at nucleotide 1111 that caused a ser371-to-cys substitution in the extracellular region of the FGFR3 protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, TER807GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913101,
|
|
|
|
|
|
|
|
ClinVar: RCV000017737, RCV000493112, RCV003155031
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By using a combination of single-strand conformation polymorphism (SSCP) and direct sequencing of amplified exons, Rousseau et al. (1995) found 3 different heterozygous base substitutions in the chain termination codon of FGFR3 in 5 of 15 patients with thanatophoric dysplasia type I (TD1; 187600) without cloverleaf skull (codon 807, nucleotides 2458 and 2460). These mutations were expected to give rise to a protein elongated by 141 amino acids, as the mRNA continues to be translated through a 423-bp region until another in-frame stop codon is reached. This would result in a highly hydrophobic domain with an alpha-helix structure at the C-terminal end of the full-length protein. This was the first report of a stop codon mutation in an FGFR gene. Absence of stop codon mutations in the healthy parents and the finding of advanced paternal age at the time of conception gave support to the view that de novo mutations of paternal origin were involved. Of the 5 patients, 2 had a T-to-G transversion in the TGA stop codon, 2 had a T-to-A transversion in the TGA stop codon, and 1 had an A-to-T transversion in the TGA stop codon. The first of these mutations, TGA to GGA, represents ter807 to gly; the second, TGA to AGA, represents a ter807-to-arg change (134934.0008); and the third, TGA to TGT, represents a ter807-to-cys change (134934.0009). The classic example of a stop codon mutation is that found in the alpha-globin chain variant hemoglobin Constant Spring (141850.0001). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, TER807ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913101,
|
|
|
|
|
|
|
|
ClinVar: RCV000017738, RCV000520562, RCV002504801
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 of 15 cases of thanatophoric dysplasia type I (TD1; 187600) without cloverleaf skull, Rousseau et al. (1995) found a change in the termination codon, TGA to AGA (ter807 to arg), that resulted in a protein elongated by 141 amino acids. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, TER807CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913103,
|
|
|
|
|
|
|
|
ClinVar: RCV000017739, RCV003155032, RCV004528117
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 1 of 15 patients with TD type I without cloverleaf skull, Rousseau et al. (1995) found a change in the chain termination codon, TGA to TGT (ter807 to cys), that resulted in a protein elongated by 141 amino acids. See also 134934.0008 and Rousseau et al. (1996). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, ASN540LYS, 1620C-A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933068,
|
|
|
|
|
|
gnomAD: rs28933068,
|
|
|
|
|
|
ClinVar: RCV000017740, RCV000017771, RCV000255928, RCV000353403, RCV002273932, RCV004541008, RCV004786271
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 8 of 14 unrelated patients with hypochondroplasia (HCH; 146000), Bellus et al. (1995) found a C-to-A transversion at nucleotide 1620 of the FGFR3 gene, resulting in an asn540-to-lys (N540K) substitution in the proximal tyrosine kinase domain of the protein. This mutation was demonstrated in the severely affected woman thought to represent a hypochondroplasia/achondroplasia compound heterozygote (McKusick et al., 1973); the other allele carried the common achondroplasia mutation: gly380 to arg (134934.0001). Prinos et al. (1995) found the same mutation in 4 cases and confirmed its occurrence in the hypochondroplasia/achondroplasia compound heterozygote. </p><p>Bellus et al. (1995) referred to the nucleotide as 1620; Prinos et al. (1995) referred to the nucleotide as 1659. Both groups numbered the amino acid as 540. </p><p>Huggins et al. (1999) reported an 8-month-old girl with achondroplasia/hypochondroplasia whose father had the G380R mutation and whose mother had the N450K mutation. Chitayat et al. (1999) simultaneously reported an infant boy with achondroplasia/hypochondroplasia whose mother had the G380R mutation and whose father had the N450K mutation. Molecular analysis confirmed the compound heterozygosity of both children, who displayed an intermediate phenotype that was more severe than either condition in the heterozygous state but less severe than homozygous ACH. </p><p>Prinster et al. (1998) selected 18 patients with a phenotype compatible with hypochondroplasia based on the most common radiologic criteria. The presence of the N540K mutation was verified by restriction enzyme digestions in 9 of the 18 patients. Although similar in phenotype to patients without the mutation, these 9 had the additional feature of relative macrocephaly. Furthermore, the association of the unchanged or narrow interpedicular distance with the fibula longer than the tibia was more common in patients with the N540K mutation. </p><p>Among 65 patients with hypochondroplasia, Ramaswami et al. (1998) found that 28 (43%) were heterozygous for the 1620C-A transversion resulting in the asn540-to-lys amino acid substitution in the tyrosine kinase domain of FGFR3. </p><p>Angle et al. (1998) found the 1620C-A mutation in FGFR3 in a patient with hypochondroplasia associated with cloverleaf skull deformity. Cloverleaf skull had not previously been reported in hypochondroplasia. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 CROUZON SYNDROME WITH ACANTHOSIS NIGRICANS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, ALA391GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28931615,
|
|
|
|
|
|
gnomAD: rs28931615,
|
|
|
|
|
|
ClinVar: RCV000017726, RCV000194803, RCV000414319, RCV000623005
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 patients with Crouzon syndrome with acanthosis nigricans (612247), including a mother and daughter and 2 patients with sporadic disease, Meyers et al. (1995) identified the same heterozygous 1172C-A transversion in the FGFR3 gene, resulting in an ala391-to-glu (A391E) substitution in the transmembrane domain. The A391E mutation was not present in 16 unrelated Crouzon syndrome patients with FGFR2 mutations, 13 unrelated Crouzon syndrome patients without FGFR2 IgIII domain mutations, or 50 unrelated controls. In addition, the authors found no FGFR3 mutations in 2 unrelated patients with isolated acanthosis nigricans (100600). </p><p>Arnaud-Lopez et al. (2007) reported 2 additional unrelated girls with Crouzon syndrome with acanthosis nigricans associated with a heterozygous A391E mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, ASN540LYS, 1620C-G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28933068,
|
|
|
|
|
|
gnomAD: rs28933068,
|
|
|
|
|
|
ClinVar: RCV000017741, RCV000255372, RCV000415460, RCV000622950, RCV000763122, RCV001332222, RCV001804740, RCV002276553, RCV004737156
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with hypochondroplasia (HCH; 146000), Prinos et al. (1995) found a C-to-G transversion at nucleotide 1659 (nucleotide 1620 in the numbering system of Bellus et al. (1995)) of the FGFR3 gene, predicted to cause an asn540-to-lys (N540K) substitution. The N540K mutation causing hypochondroplasia and known to be caused by either of 2 substitutions in the same nucleotide (1620C-G and 1620C-A; 134934.0010) is comparable to the gly380-to-arg mutation which causes achondroplasia and can be due to either of 2 different mutations in the same nucleotide (see 134934.0001 and 134934.0002). </p><p>In a study of 18 Taiwanese patients with hypochondroplasia, Tsai et al. (1999) identified a C-to-A transversion at nucleotide 1659 (in their numbering system) of the FGFR3 gene in 6 patients, and a C-to-G transversion of the same nucleotide in 4 patients. The molecular basis in the remaining 8 patients was unknown. (There was discrepancy between the text of the paper and the title; the latter stated that 8 of 18 had the N540K mutation.) </p><p>Fofanova et al. (1998) studied 16 patients with hypochondroplasia, 12 familial and 4 sporadic. In 9 patients (56.3%), the heterozygous N540K mutation was detected; in 6 patients the mutation was due to 1659C-A and in 3 patients to 1659C-G. The ratios of familial and sporadic cases among patients who carried FGFR3 mutations were similar. The 7 patients who lacked the N540K mutation were all familial. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
CERVICAL CANCER, SOMATIC, INCLUDED<br />
|
|
BLADDER CANCER, SOMATIC, INCLUDED<br />
|
|
KERATOSIS, SEBORRHEIC, SOMATIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, SER249CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913483,
|
|
|
|
|
|
gnomAD: rs121913483,
|
|
|
|
|
|
ClinVar: RCV000017742, RCV000017743, RCV000017744, RCV000017745, RCV000297175, RCV000420501, RCV000763119, RCV002276554, RCV003155033, RCV003758684, RCV003989294, RCV004532377, RCV004795921
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Tavormina et al. (1995) described another cysteine-generating mutation in the extracellular domain of FGFR3: a C-to-G transversion at nucleotide 746, which changed ser249 to cys. The authors speculated that the unpaired cysteine residue in this region of the protein might result in formation of intermolecular disulfide bonds between 2 mutant FGFR3 monomers and thereby constitutively activate the receptor complex. </p><p>Of the FGFR3 mutations identified by Cappellen et al. (1999) in epithelial tumors, the ser249-to-cys somatic mutation was the most common, affecting 5 of 9 bladder cancers (109800) and 3 of 3 cervical cancers (603956). </p><p>Logie et al. (2005) identified a somatic S249C mutation in the FGFR3 gene in 5 seborrheic keratoses (182000). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 MUENKE SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
SAETHRE-CHOTZEN SYNDROME, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, PRO250ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs4647924,
|
|
|
|
|
|
gnomAD: rs4647924,
|
|
|
|
|
|
ClinVar: RCV000017746, RCV000017747, RCV000121075, RCV000193831, RCV000436385, RCV000622712, RCV000626772, RCV000987393, RCV001334261, RCV001813993, RCV002273933, RCV003483434, RCV004554603, RCV005003375
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Bellus et al. (1996) described a pro250-to-arg (P250R) amino acid substitution in FGFR3 (caused by a C-to-G transversion at position 749 of the coding cDNA sequence) in 10 unrelated patients with nonsyndromic autosomal dominant or sporadic craniosynostosis. This mutation is in the extracellular domain of the FGFR3 protein and occurs precisely at the position within the FGFR3 protein analogous to that of mutations in FGFR1 (P252R; 136350.0001) and FGFR2 (P253R; 176943.0011), previously reported in Pfeiffer (101600) and Apert syndromes, respectively. They pictured the craniofacial and extremity anomalies in some of these cases. </p><p>Muenke et al. (1997) provided extensive information on a series of 61 individuals from 20 unrelated families in which coronal craniosynostosis is due to this mutation, defining a new clinical syndrome that is referred to as Muenke nonsyndromic coronal craniosynostosis (602849). At about the same time, Moloney et al. (1997) studied 26 patients with coronal craniosynostosis but no syndromic diagnosis to determine the frequency of the 749C-G (pro250-to-arg) mutation in FGFR3. Heterozygosity for the mutation was found in 8 (31%) of the 26 probands. In 2 cases, the mutation showed autosomal dominant transmission with evidence of variable expressivity; the remaining 6 cases were sporadic. Moloney et al. (1997) pointed out that the 749C nucleotide has one of the highest mutation rates described in the human genome. </p><p>Reardon et al. (1997) reported 9 individuals with the P250R mutation. The authors documented a variable clinical presentation and contrasted this with the phenotype produced by the analogous mutation in FGFR1 (P252R; 136350.0001) and FGFR2 (P253R; 176943.0011). In particular, Reardon et al. (1997) noted mental retardation in 4 of the 9 cases, which they reported was unrelated to the management of the craniosynostosis. Reardon et al. (1997) suggested that there was a significant overlap between Saethre-Chotzen syndrome (101400), a common autosomal dominant condition of craniosynostosis and limb anomalies, and the phenotype produced by this mutation. They also noted unisutural craniosynostosis in 3 of the 9 cases to emphasize the caution with which the recurrence risks should be approached in craniosynostosis. </p><p>In a study of 32 unrelated patients with features of Saethre-Chotzen syndrome, Paznekas et al. (1998) identified 7 families with the P250R mutation of the FGFR3 gene. The overlap in clinical features and the presence, in the same genes, of mutations for more than one craniosynostotic condition, such as Saethre-Chotzen, Crouzon, and Pfeiffer syndromes, suggested that the TWIST1 gene (601622), which is most frequently the site of mutations causing Saethre-Chotzen syndrome, and FGFRs are components of the same molecular pathway involved in the modulation of craniofacial and limb development in humans. The clinical features of the patients who were referred with the possible diagnosis of Saethre-Chotzen syndrome and who were found to have the FGFR3 mutation were not obviously different from those of individuals with the TWIST1 mutation. </p><p>Golla et al. (1997) described a large German family with the P250R mutation in which there was also considerable phenotypic variability among individuals with the identical mutation. The clinical features in this family had been described by von Gernet et al. (1996). </p><p>Gripp et al. (1998) found the P250R mutation in 4 of 37 patients with synostotic anterior plagiocephaly (literally 'oblique head'). In 3 mutation-positive patients with full parental studies, a parent with an extremely mild phenotype was found to carry the same mutation. None of the 6 patients with nonsynostotic plagiocephaly and none of the 4 patients with additional suture synostosis had the FGFR3 mutation. </p><p>Hollway et al. (1998) found the P250R mutation in FGFR3 in an extensive family with craniosynostosis and deafness, extending through 5 generations. The deafness was congenital, bilateral, sensorineural, and of moderate degree. Four family members had craniosynostosis evident at clinical review; 2 required surgery, and 1 was symptomatically deaf. Thirteen other affected members of the family had no evidence of craniosynostosis but were either symptomatically deaf or required bilateral hearing aids. Hollway et al. (1998) thought that the craniosynostosis and deafness were not coincidentally associated and that the low penetrance of symptomatic craniosynostosis in this family raised the possibility that some families with the P250R mutation may present with deafness only. They pointed out that 1 locus for autosomal dominant nonsyndromal deafness (DFNA6; 600965) maps to 4p16.3, the location of the FGFR3 gene. </p><p>Robin et al. (1998) described a woman who was completely clinically and radiologically normal but was carrying the P250R mutation. Graham et al. (1998) suggested that carpal-tarsal fusion may be the most specific finding for the FGFR3 mutation, being present in some individuals who did not have craniosynostosis. The patient reported by Robin et al. (1998) did not have carpal-tarsal fusion. </p><p>Lajeunie et al. (1999) studied 62 patients with sporadic or familial forms of coronal craniosynostosis. The P250R mutation was identified in 20 probands from 27 unrelated families (74%), while only 6 of 35 sporadic cases (17%) were found to have this mutation. In both familial and sporadic cases, females were more severely affected, with 68% of females but only 35% of males having brachycephaly. In the most severely affected individuals, bicoronal craniosynostosis was associated with hypertelorism and marked bulging of the temporal fossae, features that Lajeunie et al. (1999) concluded might be helpful for clinical diagnosis. Lajeunie et al. (1999) concluded that the P250R mutation is most often familial and is associated with a more severe phenotype in females than in males. </p><p>El Ghouzzi et al. (1999) found the P250R mutation in 2 of 22 cases of Saethre-Chotzen syndrome. The largest number of cases (16/22) were found to have mutations in the TWIST1 gene. In 4 of the 22 cases, no mutations were found in either TWIST1 or FGFR3. </p><p>Roscioli et al. (2001) described a patient with severe premature calvarial synostosis and epidermal hyperplasia. Although the phenotype was consistent with that of a mild presentation of Beare-Stevenson syndrome (123790), molecular analysis of FGFR2 (176943) revealed wildtype sequence only. Molecular analysis of FGFR3 identified a heterozygous P250R missense mutation in both the proposita and her mildly affected father. The cutis gyrata in the daughter was located on the left palm, accompanied by deep skin creasing of both soles. In addition, a clearly demarcated darkened linear streak (initially macular) was present on the left forearm. At the age of 18 months, normal skin overlaid the neck and flexural regions. The father showed macrocephaly with some excessive creasing/thickening of the forehead skin and hypertelorism, but the skull was otherwise normal with no evidence of past premature craniosynostosis. This case extended the clinical spectrum of the P250R mutation to encompass epidermal hyperplasia and documented the phenomenon of activated FGFR receptors stimulating common downstream developmental pathways, resulting in overlapping clinical outcomes. </p><p>Lowry et al. (2001) reported a family in which members with coronal craniosynostosis, skeletal abnormalities of the hands, and sensorineural hearing loss had the P250R mutation. One family member also had a Sprengel shoulder anomaly (184400) and multiple cervical spine anomalies consistent with Klippel-Feil anomaly (118100). The authors reported an additional case with an identical phenotype without the mutation. </p><p>Rannan-Eliya et al. (2004) studied 19 cases of Muenke syndrome due to de novo P250R mutations in FGFR3. All 10 informative cases were of paternal origin; the average paternal age at birth for all 19 cases was 34.7 years. The authors noted that exclusive paternal origin and increased paternal age had previously been described for the G380R mutation in FGFR3 (134934.0001) and mutations in FGFR2 (e.g., S252W, 176943.0010). </p><p>By surface plasmon resonance analysis and x-ray crystallography, Ibrahimi et al. (2004) characterized the effects of proline-to-arginine mutations in FGFR1c and FGFR3c on ligand binding. Both the FGFR1c P252R and FGFR3c P250R mutations exhibited an enhancement in ligand binding in comparison to their respective wildtype receptors. Binding of both mutant receptors to FGF9 (600921) was notably enhanced and implicated FGF9 as a potential pathophysiologic ligand for mutant FGFRs in mediating craniosynostosis. The crystal structure of P252R mutant in complex with FGF2 (134920) demonstrated that enhanced ligand binding was due to an additional set of receptor-ligand hydrogen bonds, similar to those gain-of-function interactions that occur in the crystal structure of FGFR2c P253R (176943.0011) mutant in complex with FGF2. However, unlike the P253R mutant, neither the FGFR1c P250R mutant nor the FGFR3c P250R mutant bound appreciably to FGF7 (148180) or FGF10 (602115). Ibrahimi et al. (2004) suggested that this might explain why limb phenotypes observed in type I Pfeiffer syndrome and Muenke syndrome are less severe than limb abnormalities observed in Apert syndrome. </p><p>Almeida et al. (2009) reported a Portuguese patient with Muenke syndrome resulting from the P250R mutation who developed an osteochondroma in the proximal metaphysis of the left tibia. </p><p>In a cohort of 182 Spanish probands with craniosynostosis, Paumard-Hernandez et al. (2015) found the most frequent mutation to be P250R in FGFR3, which was detected in 24 patients (13.2% of the cohort). The authors noted that this was somewhat lower than the 24% detected in a UK study of craniosynostosis patients by Wilkie et al. (2010). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 ACHONDROPLASIA, SEVERE, WITH DEVELOPMENTAL DELAY AND ACANTHOSIS NIGRICANS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
THANATOPHORIC DYSPLASIA, TYPE I, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, LYS650MET
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913105,
|
|
|
|
|
|
|
|
ClinVar: RCV000017750, RCV001574416, RCV002310592, RCV002496392, RCV004558267
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated patients, Francomano et al. (1996) found the same novel FGFR3 mutation as the cause of a previously undescribed skeletal dysplasia characterized by extreme short stature, severe tibial bowing, profound developmental delay, and acanthosis nigricans (SADDAN; 616482). The mutation, a 1949A-T transversion causing a lys650-to-met (K650M) substitution, occurs in the distal tyrosine kinase domain. (A change at the adjacent nucleotide in FGFR3 (1948A-G) causes a substitution at the same codon (K650E; 134934.0004) and results in thanatophoric dysplasia type II (187601).) Both individuals with the K650M mutation, one aged 5 years and the other aged 29 years, had skeletal findings distinct from both TD1 (187600) and TD2. These included absence of craniosynostosis or cloverleaf skull anomaly and presence of moderate bowing of the femurs with reverse bowing of the tibia and fibula. The older patient had bilateral tibial pseudoarthroses. Other clinical and physical features common to both patients included survival past infancy; periods of respiratory compromise during infancy but without the need for prolonged mechanical ventilation; development of acanthosis nigricans in the cervical and flexural areas; and seizures and hydrocephalus during infancy with severe limitation of motor and intellectual development. The younger patient had structural anomalies of the brain, including a hypoplastic corpus callosum and abnormal development of the cerebellum.</p><p>Tavormina et al. (1999) referred to the distinctive syndrome described by Francomano et al. (1996) as SADDAN dysplasia, an acronym derived from 'severe achondroplasia with developmental delay and acanthosis nigricans.' They reported 4 unrelated individuals with this syndrome (2 of whom were reported by Francomano et al., 1996) approaching the severity observed in thanatophoric dysplasia type I. Different from thanatophoric dysplasia was the development of extensive areas of acanthosis nigricans beginning in early childhood in 3 patients, severe neurologic impairments, and survival past infancy without prolonged life-support measures. Lys650 is highly conserved in the kinase domain activation loop. Transient transfection studies with FGFR3 mutant constructs showed that the lys650-to-met mutation caused a dramatic increase in constitutive receptor kinase activity, approximately 3 times greater than that observed with the lys650-to-glu mutation. </p><p>Zankl et al. (2008) reported a patient with the SADDAN phenotype associated with a K650M substitution resulting from a de novo 1949A-T transversion in exon 15 of the FGFR3 gene. The patient had severe micromelia, frontal bossing, large anterior fontanel, depressed nasal bridge, reverse tibial bowing, small thorax, and hypotonia. Acanthosis nigricans was not present. He died at age 21 days due to respiratory failure. Zankl et al. (2008) noted that about half of patients reported with the K650M mutation died before 21 days of age, while others have shown longer survival. The authors also noted that acanthosis nigricans has been reported in patients with other skeletal dysplasias due to FGFR3 mutations, and thus should be considered a long-term complication rather than a specific feature of SADDAN. In addition, mental retardation only becomes apparent in long-term survivors and thus cannot be used as a diagnostic criterion for SADDAN in the neonatal period. </p><p>The K650M mutation due to a 1988A-T transversion was found in cell lines and tumors of multiple myeloma (254500) containing a karyotypically silent translocation between t(4;14) and the IgH. Chesi et al. (1997) proposed that after the t(4;14) translocation, somatic mutation during tumor progression generated an FGFR3 protein that was active in the absence of ligand. FGFR is, then, another example of a gene that can be both an oncogene and a 'teratogene.' </p><p>Kitoh et al. (1998) reported the lys650-to-met mutation as the cause of thanatophoric dysplasia type I.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, TYR373CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913485,
|
|
|
|
|
|
|
|
ClinVar: RCV000017751, RCV000255235, RCV003155034, RCV004737157
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Rousseau et al. (1996) found a tyr373-to-cys mutation (Y373C) in the FGFR3 gene accounting, together with 2 other mutations, for 73% of 26 cases of thanatophoric dysplasia type I (TD1; 187600). </p><p>Brodie et al. (1998) reported a patient with TD1 due to the Y373C mutation in FGFR3, who had soft tissue syndactyly of the fingers and toes. Syndactyly had not previously been described in thanatophoric dysplasia or other conditions with FGFR3 mutations, although it occurs in several craniosynostosis syndromes due to mutations in FGFR2 (176943), notably Apert syndrome (101200). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 MULTIPLE MYELOMA, SOMATIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, FGFR3/IGH FUSION
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000017752
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Chesi et al. (1997) identified the translocation t(4;14)(p16.3;q32.3) in 5 myeloma cell lines and in at least 3 of 10 primary tumors. Two cell lines and 1 primary tumor with this translocation selectively expressed an FGFR3 allele containing activating mutations identified previously in forms of dwarfism. Chesi et al. (1997) proposed that after the t(4;14) translocation, somatic mutation in the FGFR3 gene during tumor progression frequently generates an FGFR3 protein that is active in the absence of ligand. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, ASN540THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs77722678,
|
|
|
|
|
|
gnomAD: rs77722678,
|
|
|
|
|
|
ClinVar: RCV000017753, RCV001549822
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family in which members were affected with hypochondroplasia (HCH; 146000) in 3 generations, Deutz-Terlouw et al. (1998) found an A-to-C transversion at nucleotide 1658 of the FGFR3 gene, predicted to result in an asn540-to-thr substitution. The index patient was a 35-year-old male with mild rhizomelic limb shortening, stocky build, mild frontal bossing, and some limitation of pronation and supination of the left elbow. His height was 160 cm, his span 155.5 cm, and his skull circumference 56 cm. Radiographic examination showed short femoral necks, generalized brachydactyly, and absence of normal widening of the spinal canal in the lumbar area. Clinical findings in 2 of his 3 children and in his mother were similar. One of the affected sons also showed learning disabilities. The clinical symptoms, including macrocephaly and lumbar hyperlordosis, were more pronounced in him than in the other affected family members. The same codon was involved as in the more common asn540-to-lys mutation (134934.0010). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, ILE538VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs80053154,
|
|
|
|
|
|
gnomAD: rs80053154,
|
|
|
|
|
|
ClinVar: RCV000017754, RCV001269544, RCV004798734
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Swedish family in which 3 members had hypochondroplasia (HCH; 146000), Grigelioniene et al. (1998) found an A-to-G transition at position 1651, predicting an ile538-to-val substitution in the FGFR3 protein. The substitution occurred at a position close to the mutations in the asn540 codon (134934.0010, 134934.0018), in a stretch of 9 amino acids that is highly conserved among all human fibroblast growth factor receptors.</p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, LYS650ASN, 1950G-T
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28928868,
|
|
|
|
|
|
gnomAD: rs28928868,
|
|
|
|
|
|
ClinVar: RCV000017755, RCV003556038
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Bellus et al. (2000) demonstrated a 1950G-T mutation and a 1950G-C (134934.0021) mutation in patients with hypochondroplasia (HCH; 146000); both mutations resulted in a lys650-to-asn amino acid substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, LYS650ASN, 1950G-C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28928868,
|
|
|
|
|
|
gnomAD: rs28928868,
|
|
|
|
|
|
ClinVar: RCV000017756, RCV001269938, RCV002496393
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Bellus et al. (2000) found a lys650-to-asn mutation as the cause of hypochondroplasia (HCH; 146000), resulting from either 1950G-T (134934.0020) or 1950G-C. Several physical and radiologic features of the patients with hypochondroplasia due to the lys650-to-asn mutation were significantly milder than those in individuals with the asn540-to-lys (134934.0010) or lys650-to-met (134934.0015) mutations. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
BLADDER CANCER, SOMATIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, LYS650GLN
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000017757, RCV000144153, RCV002228032
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Bellus et al. (2000) identified a 1948A-C transversion in the FGFR3 gene, predicting a lys650-to-gln (K650Q) amino acid substitution and causing hypochondroplasia (HCH; 146000) in a form milder than that seen in individuals with the asn540-to-lys (134934.0010) or lys650-to-met (134934.0015) mutations. </p><p>Heuertz et al. (2006) identified the K560Q mutation in a patient with a moderate form of hypochondroplasia. </p><p>Leroy et al. (2007) identified the K650Q mutation in a patient with a mild form of hypochondroplasia who was also diagnosed with acanthosis nigricans at 8 years of age. Leroy et al. (2007) stated that the mutation is located in the second part (3-prime side) of the split tyrosine kinase domain in the intracellular portion of the single-pass transmembrane of the receptor and that it unfavorably modulates the receptor's physiologic downstream inhibitory signaling. </p><p>Sibley et al. (2001) found the same mutation, which they designated LYS652GLN (K652Q), in a transitional cell carcinoma of the bladder (109800). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, ASN540SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs77722678,
|
|
|
|
|
|
gnomAD: rs77722678,
|
|
|
|
|
|
ClinVar: RCV000017758, RCV000623459, RCV001269614, RCV002262566, RCV002273934
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Mortier et al. (2000) reported a father and daughter with clinical and radiographic features of hypochondroplasia who were heterozygous for an A-to-G transition resulting in the replacement of an asparagine residue at position 540 by a serine residue (N540S). Both individuals were mildly affected. The father's height was between the 3rd and 25th centile; he had short limbs and relative macrocephaly. Radiographs showed definite features of hypochondroplasia. The daughter was below the 3rd centile in height with short limbs, frontal bossing, and lumbar hyperlordosis. Radiographic features were subtle. </p><p>Thauvin-Robinet et al. (2003) described a family in which the N540S mutation was present in 2 brothers and their father. The proband was a 2-month-old boy referred for assessment of short limbs and macrocephaly. His brother, age 2.5 years, showed a height within the normal limits but macrocephaly with frontal bossing and mild micromelia were evident. Family history indicated micromelia and macrocephaly in the paternal grandfather (height, 163 cm) and the father's sister. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-text-font">
|
|
<strong>.0024 MOVED TO 134934.0022</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 COLORECTAL CANCER, SOMATIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, GLU322LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913111,
|
|
|
|
|
|
|
|
ClinVar: RCV000017761
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a primary colorectal cancer (114500), Jang et al. (2001) found a G-to-A transition in the FGFR3 gene, converting codon 322 from glu to lys. Glu322 is a highly conserved residue not only within the FGFR family but throughout evolution from yeast to human. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 COLORECTAL CANCER, SOMATIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, 1-BP DEL, 849C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587776836,
|
|
|
|
|
|
|
|
ClinVar: RCV000017762
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a primary colorectal cancer (114500), Jang et al. (2001) found a 1-bp deletion (849delC) in exon 7 of the FGFR3 gene causing a frameshift and premature termination. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 ACHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, GLY380ARG AND LEU377ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606809,
|
|
|
|
|
|
gnomAD: rs267606809,
|
|
|
|
|
|
ClinVar: RCV000017724, RCV000017763, RCV000029207, RCV000255750, RCV000763121, RCV001266979, RCV001807732, RCV002231193, RCV002276551, RCV003227605, RCV004545731, RCV004783725, RCV004798732
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Dutch infant with a severe form of achondroplasia (ACH; 100800), Rump et al. (2006) identified 2 de novo mutations in the FGFR3 gene on the same allele. One was the common G380R mutation (134934.0001), and the other was a 1130T-G transversion, resulting in a leu377-to-arg (L377R) substitution within the transmembrane domain. Allele-specific PCR analysis confirmed that the 2 mutations were in cis. From birth, the child had severe respiratory difficulties with multiple hypoxic episodes due to a combination of upper airway obstruction, pulmonary hypoplasia, and cervicomedullary compression. He eventually became ventilator dependent and died at age 4 months. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 LADD SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, ASP513ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913112,
|
|
|
|
|
|
gnomAD: rs121913112,
|
|
|
|
|
|
ClinVar: RCV001580446, RCV003226161, RCV004558268, RCV004786272
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Turkish father and his 2 childen with LADD syndrome (LADD2; 620192), Rohmann et al. (2006) identified a heterozygous missense mutation in the FGFR3 gene: 1537G-A in exon 11, leading to an asn513-to-asn (D513N) substitution in the conserved tyrosine kinase-1 (TK1) domain. The mutation occurred de novo in the affected father and was subsequently transmitted to his affected offspring. The D513N mutation is located in a loop that connects the beta-3 sheet to the alpha-C helix of the tyrosine kinase core. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 CAMPTODACTYLY, TALL STATURE, AND HEARING LOSS SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, ARG621HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913113,
|
|
|
|
|
|
gnomAD: rs121913113,
|
|
|
|
|
|
ClinVar: RCV000017765, RCV002228033
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In all affected members of a family with CATSHL syndrome (CATSHL; 610474), Toydemir et al. (2006) identified heterozygosity for a 1862G-A transition in the FGFR3 gene, resulting in an arg621-to-his (R621H) substitution. The mutation occurred in the catalytic loop of the tyrosine kinase domain and predicted partial loss of protein function. The mutation was not found in any unaffected members of the family or in 500 control chromosomes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 ACHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
HYPOCHONDROPLASIA, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, SER279CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913114,
|
|
|
|
|
|
gnomAD: rs121913114,
|
|
|
|
|
|
ClinVar: RCV000017766, RCV000017767, RCV000730955
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Achondroplasia</em></strong></p><p>
|
|
In a boy with achondroplasia (ACH; 100800) who was negative for the common G380R mutation (134934.0001), Heuertz et al. (2006) identified heterozygosity for a de novo 835A-C transversion in exon 7 of the FGFR3 gene, resulting in an ser279-to-cys (S279C) substitution in the IgIIIa extracellular domain. In addition to the typical skeletal features of ACH, the child had epilepsy and moderate learning difficulties. Severe kyphoscoliosis required surgical correction at age 7 years, which was complicated by postoperative lower limb paralysis requiring decompressive surgery. </p><p><strong><em>Hypochondroplasia</em></strong></p><p>
|
|
Friez and Wilson (2008) identified the S279C mutation in a newborn originally diagnosed with achondroplasia whose phenotype evolved into a milder form of hypochondroplasia (HCH; 146000) in early childhood. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, TYR278CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913115,
|
|
|
|
|
|
|
|
ClinVar: RCV000017768, RCV000415056, RCV002513085
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 30-year-old woman with hypochondroplasia (HCH; 146000), Heuertz et al. (2006) identified heterozygosity for a de novo 833A-G transition in exon 7 of the FGFR3 gene, resulting in a tyr278-to-cys (Y278C) substitution in the IgIIIa extracellular domain. The patient was born with an achondroplasia-like phenotype which changed to typical hypochondroplasia with normal craniofacial features by 3.5 years of age. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0032 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, SER84LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913116,
|
|
|
|
|
|
|
|
ClinVar: RCV000017769, RCV000850610, RCV001334259, RCV002513086
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 4-generation family with a moderate hypochondroplasia phenotype (HCH; 146000), Heuertz et al. (2006) identified heterozygosity for a 251C-T transition in exon 3 of the FGFR3 gene, resulting in a ser84-to-leu (S84L) substitution in the IgI extracellular domain. The mutation was not found in unaffected family members. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0033 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
NEVUS, EPIDERMAL, SOMATIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, GLY370CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913479,
|
|
|
|
|
|
gnomAD: rs121913479,
|
|
|
|
|
|
ClinVar: RCV000017770, RCV000029208, RCV000413645, RCV003493410, RCV003989295, RCV004668734, RCV005025064
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Thanatophoric Dysplasia, Type I</em></strong></p><p>
|
|
Rousseau et al. (1996) identified a gly370-to-cys (G370C) mutation accounting for 1 of 26 cases of thanatophoric dysplasia type I (TD1; 187600). </p><p><strong><em>Nevus, Epidermal, Somatic</em></strong></p><p>
|
|
Hafner et al. (2006) analyzed the FGFR3 gene in 39 common epidermal nevi (162900) from 33 patients and identified mosaicism for a double mutation in exon 10 of the FGFR3 gene in 1 patient: the G372C mutation and the G382R (G380R; 134934.0001) mutation. Codons were numbered according to the FGFR3 IIIb isoform. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0034 THANATOPHORIC DYSPLASIA, TYPE I</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, ASN540LYS AND GLN485ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs267606808,
|
|
|
|
|
|
|
|
ClinVar: RCV000017740, RCV000017771, RCV000255928, RCV000353403, RCV002273932, RCV004541008, RCV004786271
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a fetus with lethal thanatophoric dysplasia I (TD1; 187600), Pannier et al. (2009) identified 2 de novo heterozygous mutations in the FGFR3 gene on the same allele: N540K (134934.0010), and a 1454A-G transition, resulting in a gln485-to-arg (Q485R) substitution at a conserved residue in the beta-2 strand in the kinase domain. Protein modeling suggested that the mutations altered the receptor structure, holding it in a fully activated state, consistent with a gain of function. The pregnancy was terminated at 24 weeks' gestation after the fetus was noted to have severe dwarfism. Radiographic studies showed severe rhizomelic shortness of the long bones and mild bowing of the femora, radii, and ulnae. The spine showed severe platyspondyly with H-shaped vertebrae and narrowing of the interpediculate distance. The thorax was small with short ribs, and the iliac bones were short and wide. Macrocrania and frontal bossing were observed; there was no evidence of a cloverleaf skull. Postmortem examination showed cerebral cortical malformations and severe disorganization of growth plates in the long bones. The N540K mutation in isolation usually results in the less severe phenotype of hypochondroplasia (HCH; 146000). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0035 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, ALA334THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs373496046,
|
|
|
|
|
|
gnomAD: rs373496046,
|
|
|
|
|
|
ClinVar: RCV000022552
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant is classified as a variant of unknown significance because its contribution to a craniosynostosis phenotype has not been confirmed.</p><p>In a Spanish boy with mild isolated craniosynostosis, but an inconclusive skull radiograph, Barroso et al. (2011) identified a heterozygous 1000G-A transition in exon 8 of the FGFR3 gene, resulting in an ala334-to-thr (A334T) substitution at a conserved residue just before the beta-F loop of the IgIII domain of FGFR3C. The mutation was not found in 188 Spanish control individuals. The proband, who was delivered prematurely at 29 weeks' gestation, was noted at birth to have turri/brachycephaly with caput succedaneum. However, the cranial deformity corrected itself within the first 4 months of life and he showed normal psychomotor development. At age 5.5 years, he had a disproportionately large head compared to his body, but head circumference was in the normal range. His head appeared slightly scaphocephalic, he had a tall, broad forehead with a slightly prominent metopic suture, and mild hypertelorism with somewhat downward slanting palpebral fissures. The mother, who also carried the A334T variant, had even milder features, with a high, broad forehead, apparent mild hypertelorism, and the appearance of a large head, but normal head circumference. The maternal grandfather, who also carried the variant, had similar cranial features to the mother, but measurements were not done. All had normal height. No functional studies on the A334T variant were performed. Barroso et al. (2011) suggested that the A334T variant was responsible for the phenotype because the equivalent variant in FGFR2, A337T (176943.0042), was found in a proband with unicoronal synostosis; however, that variant was also found in 6 unaffected members of the proband's family (Wilkie et al., 2007). Barroso et al. (2011) noted that another FGFR2 variant at the same residue (A337P; 176943.0041) was found in a patient with Crouzon syndrome (123500), again suggesting that the FGFR3 A334T variant may have pathogenic potential. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0036 HYPOCHONDROPLASIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, GLY342CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587778775,
|
|
|
|
|
|
gnomAD: rs587778775,
|
|
|
|
|
|
ClinVar: RCV000056066
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 25-year-old Chinese woman with hypochondroplasia (HCH; 146000) who had short extremities, relative macrocephaly, frontal bossing, and genu varum, Wang et al. (2013) identified a heterozygous c.1024G-T transversion in the FGFR3 gene, resulting in a gly342-to-cys (G342C) substitution at a conserved residue in the IgIII loop. The mutation was found by exome sequencing and confirmed by Sanger sequencing. The mutation was also found in the woman's fetus after ultrasound showed abnormally short femur at 28 weeks' gestation. The unaffected father did not have the mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0037 CAMPTODACTYLY, TALL STATURE, AND HEARING LOSS SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, THR546LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs587777857,
|
|
|
|
|
|
|
|
ClinVar: RCV000144699
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers, born of consanguineous Egyptian parents, with camptodactyly, tall stature, and hearing loss (CATSHL; 610474), Makrythanasis et al. (2014) identified a homozygous c.1637C-A transversion in exon 12 of the FGFR3 gene, resulting in a thr546-to-lys (T546K) substitution at a conserved residue in the protein kinase domain. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was filtered against the dbSNP (build 135), 1000 Genomes Project, and Exome Variant Server databases and was not found in 50 control individuals of the same ethnic origin. Functional studies of the variant were not performed, but the authors postulated a loss-of-function effect. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0038 LADD SYNDROME 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
FGFR3, ASP628ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1453271838,
|
|
|
|
|
|
|
|
ClinVar: RCV004559335, RCV004597852
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 23-year-old proband and his affected mother in a consanguineous Iranian family with LADD syndrome (LADD2; 620192), Talebi et al. (2017) identified a heterozygous c.1882G-A transition in exon 14 of the FGFR3 gene, resulting in an asp628-to-asn (D628N) substitution at a highly conserved residue in the cytoplasmic tyrosine kinase domain. The mutation, which was found by next-generation sequencing and confirmed by Sanger sequencing, was not present in the unaffected father or in 400 control chromosomes. No functional studies were reported. </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">
|
|
Almeida, M. R., Campos-Xavier, A. B., Medeira, A., Cordeiro, I., Sousa, A. B., Lima, M., Soares, G., Rocha, M., Saraiva, J., Ramos, L., Sousa, S., Marcelino, J. P., Correia, A., Santos, H. G.
|
|
<strong>Clinical and molecular diagnosis of the skeletal dysplasias associated with mutations in the gene encoding fibroblast growth factor receptor 3 (FGFR3) in Portugal.</strong>
|
|
Clin. Genet. 75: 150-156, 2009.
|
|
|
|
|
|
[PubMed: 19215249]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2008.01123.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Angle, B., Hersh, J. H., Christensen, K. M.
|
|
<strong>Molecularly proven hypochondroplasia with cloverleaf skull deformity: a novel association.</strong>
|
|
Clin. Genet. 54: 417-420, 1998.
|
|
|
|
|
|
[PubMed: 9842995]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1998.tb03756.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Arnaud-Lopez, L., Fragoso, R., Mantilla-Capacho, J., Barros-Nunez, P.
|
|
<strong>Crouzon with acanthosis nigricans: further delineation of the syndrome.</strong>
|
|
Clin. Genet. 72: 405-410, 2007.
|
|
|
|
|
|
[PubMed: 17935505]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2007.00884.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Avraham, K. B., Givol, D., Avivi, A., Yayon, A., Copeland, N. G., Jenkins, N. A.
|
|
<strong>Mapping of murine fibroblast growth factor receptors refines regions of homology between mouse and human chromosomes.</strong>
|
|
Genomics 21: 656-658, 1994.
|
|
|
|
|
|
[PubMed: 7959747]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1994.1330]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Barroso, E., Perez-Carrizosa, V., Garcia-Recuero, I., Glucksman, M. J., Wilkie, A. O., Garcia-Minaur, S., Heath, K. E.
|
|
<strong>Mild isolated craniosynostosis due to a novel FGFR3 mutation, p.Ala334Thr.</strong>
|
|
Am. J. Med. Genet. 155A: 3050-3053, 2011.
|
|
|
|
|
|
[PubMed: 22038757]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.34199]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bellus, G. A., Gaudenz, K., Zackai, E. H., Clarke, L. A., Szabo, J., Francomano, C. A., Muenke, M.
|
|
<strong>Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes.</strong>
|
|
Nature Genet. 14: 174-176, 1996.
|
|
|
|
|
|
[PubMed: 8841188]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1096-174]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bellus, G. A., Hefferon, T. W., Ortiz de Luna, R. I., Hecht, J. T., Horton, W. A., Machado, M., Kaitila, I., McIntosh, I., Francomano, C. A.
|
|
<strong>Achondroplasia is defined by recurrent G380R mutations of FGFR3.</strong>
|
|
Am. J. Hum. Genet. 56: 368-373, 1995.
|
|
|
|
|
|
[PubMed: 7847369]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bellus, G. A., McIntosh, I., Smith, E. A., Aylsworth, A. S., Kaitila, I., Horton, W. A., Greenhaw, G. A., Hecht, J. T., Francomano, C. A.
|
|
<strong>A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia.</strong>
|
|
Nature Genet. 10: 357-359, 1995.
|
|
|
|
|
|
[PubMed: 7670477]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0795-357]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bellus, G. A., Spector, E. B., Speiser, P. W., Weaver, C. A., Garber, A. T., Bryke, C. R., Israel, J., Rosengren, S. S., Webster, M. K., Donoghue, D. J., Francomano, C. A.
|
|
<strong>Distinct missense mutations of the FGFR3 lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype.</strong>
|
|
Am. J. Hum. Genet. 67: 1411-1421, 2000.
|
|
|
|
|
|
[PubMed: 11055896]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/316892]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bergsagel, P. L., Chesi, M., Nardini, E., Brents, L. A., Kirby, S. L., Kuehl, W. M.
|
|
<strong>Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma.</strong>
|
|
Proc. Nat. Acad. Sci. 93: 13931-13936, 1996.
|
|
|
|
|
|
[PubMed: 8943038]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.93.24.13931]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brodie, S. G., Kitoh, H., Lachman, R. S., Nolasco, L. M., Mekikian, P. B., Wilcox, W. R.
|
|
<strong>Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by FGFR3 mutations.</strong>
|
|
Am. J. Med. Genet. 84: 476-480, 1999.
|
|
|
|
|
|
[PubMed: 10360402]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brodie, S. G., Kitoh, H., Lipson, M., Sifry-Platt, M., Wilcox, W. R.
|
|
<strong>Thanatophoric dysplasia type I with syndactyly.</strong>
|
|
Am. J. Med. Genet. 80: 260-262, 1998.
|
|
|
|
|
|
[PubMed: 9843049]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8628(19981116)80:3<260::aid-ajmg15>3.0.co;2-s]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cappellen, D., De Oliveira, C., Ricol, D., Gil Diez de Medina, S., Bourdin, J., Sastre-Garau, X., Chopin, D., Thiery, J. P., Radvanyi, F.
|
|
<strong>Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. (Letter)</strong>
|
|
Nature Genet. 23: 18-20, 1999.
|
|
|
|
|
|
[PubMed: 10471491]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/12615]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, L., Adar, R., Yang, X., Monsonego, E. O., Li, C., Hauschka, P. V., Yayon, A., Deng, C.-X.
|
|
<strong>Gly369-to-cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis.</strong>
|
|
J. Clin. Invest. 104: 1517-1525, 1999.
|
|
|
|
|
|
[PubMed: 10587515]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI6690]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, L., Li, C., Qiao, W., Xu, X., Deng, C.
|
|
<strong>A ser365-cys mutation of fibroblast growth factor receptor 3 in mouse downregulates Ihh/PTHrP signals and causes severe achondroplasia.</strong>
|
|
Hum. Molec. Genet. 10: 457-465, 2001.
|
|
|
|
|
|
[PubMed: 11181569]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.5.457]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chesi, M., Nardini, E., Brents, L. A., Schrock, E., Ried, T., Kuehl, W. M., Bergsagel, P. L.
|
|
<strong>Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3.</strong>
|
|
Nature Genet. 16: 260-264, 1997.
|
|
|
|
|
|
[PubMed: 9207791]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0797-260]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chitayat, D., Fernandez, B., Gardner, A., Moore, L., Glance, P., Dunn, M., Chun, K., Sgro, M., Ray, P., Allingham-Hawkins, D.
|
|
<strong>Compound heterozygosity for the achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome.</strong>
|
|
Am. J. Med. Genet. 84: 401-405, 1999.
|
|
|
|
|
|
[PubMed: 10360393]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cho, J. Y., Guo, C., Torello, M., Lunstrum, G. P., Iwata, T., Deng, C., Horton, W. A.
|
|
<strong>Defective lysosomal targeting of activated fibroblast growth factor receptor 3 in achondroplasia.</strong>
|
|
Proc. Nat. Acad. Sci. 101: 609-614, 2004.
|
|
|
|
|
|
[PubMed: 14699054]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.2237184100]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Colvin, J. S., Bohne, B. A., Harding, G. W., McEwen, D. G., Ornitz, D. M.
|
|
<strong>Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3.</strong>
|
|
Nature Genet. 12: 390-397, 1996.
|
|
|
|
|
|
[PubMed: 8630492]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0496-390]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Davidson, D., Blanc, A., Filion, D., Wang, H., Plut, P., Pfeffer, G., Buschmann, M. D., Henderson, J. E.
|
|
<strong>Fibroblast growth factor (FGF) 18 signals through FGF receptor 3 to promote chondrogenesis.</strong>
|
|
J. Biol. Chem. 280: 20509-20515, 2005.
|
|
|
|
|
|
[PubMed: 15781473]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M410148200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Deng, C., Wynshaw-Boris, A., Zhou, F., Kuo, A., Leder, P.
|
|
<strong>Fibroblast growth factor receptor 3 is a negative regulator of bone growth.</strong>
|
|
Cell 84: 911-921, 1996.
|
|
|
|
|
|
[PubMed: 8601314]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)81069-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Deutz-Terlouw, P. P., Losekoot, M., Aalfs, C. M., Hennekam, R. C. M., Bakker, E.
|
|
<strong>Asn540thr substitution in the fibroblast growth factor receptor 3 tyrosine kinase domain causing hypochondroplasia.</strong>
|
|
Hum. Mutat. Suppl. 1: S62-S65, 1998.
|
|
|
|
|
|
[PubMed: 9452043]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1380110122]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
El Ghouzzi, V., Lajeunie, E., Le Merrer, M., Cormier-Daire, V., Renier, D., Munnich, A., Bonaventure, J.
|
|
<strong>Mutations within or upstream of the basic helix-loop-helix domain of the TWIST gene are specific to Saethre-Chotzen syndrome.</strong>
|
|
Europ. J. Hum. Genet. 7: 27-33, 1999.
|
|
|
|
|
|
[PubMed: 10094188]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5200240]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eswarakumar, V. P., Schlessinger, J.
|
|
<strong>Skeletal overgrowth is mediated by deficiency in a specific isoform of fibroblast growth factor receptor 3.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 3937-3942, 2007.
|
|
|
|
|
|
[PubMed: 17360456]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0700012104]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fofanova, O. V., Takamura, N., Kinoshita, E., Meerson, E. M., Iljina, V. K., Nechvolodova, O. L., Evgrafov, O. V., Peterkova, V. A., Yamashita, S.
|
|
<strong>A missense mutation of C1659 in the fibroblast growth factor receptor 3 gene in Russian patients with hypochondroplasia.</strong>
|
|
Endocr. J. 45: 791-795, 1998.
|
|
|
|
|
|
[PubMed: 10395236]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1507/endocrj.45.791]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Francomano, C. A., Bellus, G. A., Szabo, J., McIntosh, I., Dorst, J., Lee, R., Hurko, O., Fraley, A. E., Bamshad, M. J.
|
|
<strong>A new skeletal dysplasia with severe tibial bowing, profound developmental delay and acanthosis nigricans is caused by a Lys 650 Met mutation in fibroblast growth factor receptor 3 (FGFR3). (Abstract)</strong>
|
|
Am. J. Hum. Genet. 59 (suppl.): A25 only, 1996.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Frattini, V., Pagnotta, S. M., Tala, Fan, J. J., Russo, M. V., Lee, S. B., Garofano, L., Zhang, J., Shi, P., Lewis, G., Sanson, H., Frederick, V., and 11 others.
|
|
<strong>A metabolic function of FGFR3-TACC3 gene fusions in cancer.</strong>
|
|
Nature 553: 222-227, 2018.
|
|
|
|
|
|
[PubMed: 29323298]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature25171]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Friez, M. J., Wilson, J. A. P.
|
|
<strong>Novel FGFR3 mutations in exon 7 and implications for expanded screening of achondroplasia and hypochondroplasia: a response to Heuertz et al. (Letter)</strong>
|
|
Europ. J. Hum. Genet. 16: 277-278, 2008.
|
|
|
|
|
|
[PubMed: 17895900]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5201931]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Garcia-Vargas, A., Hafner, C., Perez-Rodriguez, A. G., Rodriguez-Rojas, L. X., Gonzalez-Esqueda, P., Stoehr, R., Hernandez-Torres, M., Happle, R.
|
|
<strong>An epidermal nevus syndrome with cerebral involvement caused by a mosaic FGFR3 mutation.</strong>
|
|
Am. J. Med. Genet. 146A: 2275-2279, 2008.
|
|
|
|
|
|
[PubMed: 18642369]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.32429]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Golla, A., Lichmer, P., von Gernet, S., Winterpacht, A., Fairley, J., Murken, J., Schuffenhauer, S.
|
|
<strong>Phenotypic expression of the fibroblast growth factor receptor 3 (FGFR3) mutation P250R in a large craniosynostosis family.</strong>
|
|
J. Med. Genet. 34: 683-684, 1997.
|
|
|
|
|
|
[PubMed: 9279764]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.34.8.683]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goriely, A., Hansen, R. M. S., Taylor, I. B., Olesen, I. A., Jacobsen, G. K., McGowan, S. J., Pfeifer, S. P., McVean, G. A. T., Rajpert-De Meyts, E., Wilkie, A. O. M.
|
|
<strong>Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors.</strong>
|
|
Nature Genet. 41: 1247-1252, 2009.
|
|
|
|
|
|
[PubMed: 19855393]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.470]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Graham, J. M., Jr., Braddock, S. R., Mortier, G. R., Lachman, R., Van Dop, C., Jabs, E. W.
|
|
<strong>Syndrome of coronal craniosynostosis with brachydactyly and carpal tarsal coalition due to Pro250Arg mutation in FGFR3 gene.</strong>
|
|
Am. J. Med. Genet. 77: 322-329, 1998.
|
|
|
|
|
|
[PubMed: 9600744]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8628(19980526)77:4<322::aid-ajmg14>3.0.co;2-k]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Grigelioniene, G., Hagenas, L., Eklof, O., Neumeyer, L., Haereid, P. E., Anvret, M.
|
|
<strong>A novel missense mutation ile538-to-val in the fibroblast growth factor receptor 3 in hypochondroplasia. (Abstract)</strong>
|
|
Hum. Mutat. 11: 333 only, 1998.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gripp, K. W., McDonald-McGinn, D. M., Gaudenz, K., Whitaker, L. A., Bartlett, S. P., Glat, P. M., Cassileth, L. B., Mayro, R., Zackai, E. H., Muenke, M.
|
|
<strong>Identification of a genetic cause for isolated unilateral coronal synostosis: a unique mutation in the fibroblast growth factor receptor 3.</strong>
|
|
J. Pediat. 132: 714-716, 1998.
|
|
|
|
|
|
[PubMed: 9580776]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(98)70366-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hafner, C., van Oers, J. M. M., Vogt, T., Landthaler, M., Stoehr, R., Blaszyk, H., Hofstaedter, F., Zwarthoff, E. C., Hartmann, A.
|
|
<strong>Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi.</strong>
|
|
J. Clin. Invest. 116: 2201-2207, 2006.
|
|
|
|
|
|
[PubMed: 16841094]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI28163]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
He, L., Horton, W., Hristova, K.
|
|
<strong>Physical basis behind achondroplasia, the most common form of human dwarfism.</strong>
|
|
J. Biol. Chem. 285: 30103-30114, 2010.
|
|
|
|
|
|
[PubMed: 20624921]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M109.094086]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
He, L., Shobnam, N., Wimley, W. C., Hristova, K.
|
|
<strong>FGFR3 heterodimerization in achondroplasia, the most common form of human dwarfism.</strong>
|
|
J. Biol. Chem. 286: 13272-13281, 2011.
|
|
|
|
|
|
[PubMed: 21324899]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M110.205583]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Henderson, J. E., Naski, M. C., Aarts, M. M., Wang, D., Cheng, L., Goltzman, D., Ornitz, D. M.
|
|
<strong>Expression of FGFR3 with the G380R achondroplasia mutation inhibits proliferation and maturation of CFK2 chondrocytic cells.</strong>
|
|
J. Bone Miner. Res. 15: 155-165, 2000.
|
|
|
|
|
|
[PubMed: 10646125]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1359/jbmr.2000.15.1.155]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Henderson, S., Sillence, D., Loughlin, J., Bennetts, B., Sykes, B.
|
|
<strong>Germline and somatic mosaicism in achondroplasia.</strong>
|
|
J. Med. Genet. 37: 956-958, 2000.
|
|
|
|
|
|
[PubMed: 11186939]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.37.12.956]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Heuertz, S., Le Merrer, M., Zabel, B., Wright, M., Legeai-Mallet, L., Cormier-Daire, V., Gibbs, L., Bonaventure, J.
|
|
<strong>Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia.</strong>
|
|
Europ. J. Hum. Genet. 14: 1240-1247, 2006. Note: Erratum: Europ. J. Hum. Genet. 14: 1321 only, 2006.
|
|
|
|
|
|
[PubMed: 16912704]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5201700]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hollway, G. E., Suthers, G. K., Battese, K. M., Turner, A. M., David, D. J., Mulley, J. C.
|
|
<strong>Deafness due to pro250-to-arg mutation of FGFR3. (Letter)</strong>
|
|
Lancet 351: 877-878, 1998.
|
|
|
|
|
|
[PubMed: 9525367]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0140-6736(98)24012-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Huggins, M. J., Smith, J. R., Chun, K., Ray, P. N., Shah, J. K., Whelan, D. T.
|
|
<strong>Achondroplasia-hypochondroplasia complex in a newborn infant.</strong>
|
|
Am. J. Med. Genet. 84: 396-400, 1999.
|
|
|
|
|
|
[PubMed: 10360392]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hyland, V. J., Robertson, S. P., Flanagan, S., Savarirayan, R., Roscioli, T., Masel, J., Hayes, M., Glass, I. A.
|
|
<strong>Somatic and germline mosaicism for a R248C missense mutation in FGFR3, resulting in a skeletal dysplasia distinct from thanatophoric dysplasia.</strong>
|
|
Am. J. Med. Genet. 120A: 157-168, 2003.
|
|
|
|
|
|
[PubMed: 12833394]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.20012]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ibrahimi, O. A., Zhang, F., Eliseenkova, A. V., Linhardt, R. J., Mohammadi, M.
|
|
<strong>Proline to arginine mutations in FGF receptors 1 and 3 result in Pfeiffer and Muenke craniosynostosis syndromes through enhancement of FGF binding affinity.</strong>
|
|
Hum. Molec. Genet. 13: 69-78, 2004.
|
|
|
|
|
|
[PubMed: 14613973]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddh011]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ikegawa, S., Fukushima, Y., Isomura, M., Takada, F., Nakamura, Y.
|
|
<strong>Mutations of the fibroblast growth factor receptor-3 gene in one familial and six sporadic cases of achondroplasia in Japanese patients.</strong>
|
|
Hum. Genet. 96: 309-311, 1995.
|
|
|
|
|
|
[PubMed: 7649548]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00210413]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Intini, D., Baldini, L., Fabris, S., Lombardi, L., Ciceri, G., Maiolo, A. T., Neri, A.
|
|
<strong>Analysis of FGFR3 gene mutations in multiple myeloma patients with t(4;14).</strong>
|
|
Brit. J. Haemat. 114: 362-364, 2001.
|
|
|
|
|
|
[PubMed: 11529856]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.2001.02957.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Iwata, T., Chen, L., Li, C., Ovchinnikov, D. A., Behringer, R. R., Francomano, C. A., Deng, C.-X.
|
|
<strong>A neonatal lethal mutation in FGFR3 uncouples proliferation and differentiation of growth plate chondrocytes in embryos.</strong>
|
|
Hum. Molec. Genet. 9: 1603-1613, 2000.
|
|
|
|
|
|
[PubMed: 10861287]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/9.11.1603]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Iwata, T., Li, C.-L., Deng, C.-X., Francomano, C. A.
|
|
<strong>Highly activated Fgfr3 with the K644M mutation causes prolonged survival in severe dwarf mice.</strong>
|
|
Hum. Molec. Genet. 10: 1255-1264, 2001.
|
|
|
|
|
|
[PubMed: 11406607]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.12.1255]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jacky, B. P. S., Garay, P. E., Dupuy, J., Nelson, J. B., Cai, B., Molina, Y., Wang, J., Steward, L. E., Broide, R. S., Francis, J., Aoki, K. R., Stevens, R. C., Fernandez-Salas, E.
|
|
<strong>Identification of fibroblast growth factor receptor 3 (FGFR3) as a protein receptor for botulinum neurotoxin serotype A (BoNT/A).</strong>
|
|
PLoS Pathog. 9: e1003369, 2013. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 23696738]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1371/journal.ppat.1003369]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jang, J.-H., Shin, K.-H., Park, J.-G.
|
|
<strong>Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers.</strong>
|
|
Cancer Res. 61: 3541-3543, 2001.
|
|
|
|
|
|
[PubMed: 11325814]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jang, J.-H.
|
|
<strong>Identification and characterization of soluble isoform of fibroblast growth factor receptor 3 in human SaOS-2 osteosarcoma cells.</strong>
|
|
Biochem. Biophys. Res. Commun. 292: 378-382, 2002.
|
|
|
|
|
|
[PubMed: 11906172]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.2002.6668]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Karoui, M., Hofmann-Radvanyi, H., Zimmermann, U., Couvelard, A., Degott, C., Faridoni-Laurens, L., Ahomadegbe, J.-C., Gazzeri, S., Brambilla, E., Clerici, T., Charbonnier, P., Tresallet, C., and 8 others.
|
|
<strong>No evidence of somatic FGFR3 mutation in various types of carcinoma.</strong>
|
|
Oncogene 20: 5059-5061, 2001.
|
|
|
|
|
|
[PubMed: 11526491]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.onc.1204651]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Keegan, K., Johnson, D. E., Williams, L. T., Hayman, M. J.
|
|
<strong>Isolation of an additional member of the fibroblast growth factor receptor family, FGFR-3.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 1095-1099, 1991.
|
|
|
|
|
|
[PubMed: 1847508]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.88.4.1095]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kimura, T., Suzuki, H., Ohashi, T., Kiyota, H., Eto, Y.
|
|
<strong>The incidence of thanatophoric dysplasia mutations in FGFR3 bladder carcinomas.</strong>
|
|
Cancer 92: 2555-2561, 2001. Note: Erratum: Cancer 94: 2117 only, 2002.
|
|
|
|
|
|
[PubMed: 11745189]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1097-0142(20011115)92:10<2555::aid-cncr1607>3.0.co;2-m]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kitoh, H., Brodie, S. G., Kupke, K. G., Lachman, R. S., Wilcox, W. R.
|
|
<strong>Lys650-to-met substitution in the tyrosine kinase domain of the fibroblast growth factor receptor gene causes thanatophoric dysplasia type I. (Abstract)</strong>
|
|
Hum. Mutat. 12: 362-363, 1998.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lajeunie, E., El Ghouzzi, V., Le Merrer, M., Munnich, A., Bonaventure, J., Renier, D.
|
|
<strong>Sex related expressivity of the phenotype in coronal craniosynostosis caused by the recurrent P250R FGFR3 mutation.</strong>
|
|
J. Med. Genet. 36: 9-13, 1999.
|
|
|
|
|
|
[PubMed: 9950359]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lanning, R. W., Brown, C. A.
|
|
<strong>An improved methodology for the detection of the common mutation in the FGFR3 gene responsible for achondroplasia.</strong>
|
|
Hum. Mutat. 10: 496-499, 1997.
|
|
|
|
|
|
[PubMed: 9401015]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1997)10:6<496::AID-HUMU13>3.0.CO;2-V]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Leroy, J. G., Nuytinck, L., Lambert, J., Naeyaert, J.-M., Mortier, G. R.
|
|
<strong>Acanthosis nigricans in a child with mild osteochondrodysplasia and K650Q mutation in the FGFR3 gene.</strong>
|
|
Am. J. Med. Genet. 143A: 3144-3149, 2007.
|
|
|
|
|
|
[PubMed: 18000903]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31966]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, C., Chen, L., Iwata, T., Kitagawa, M., Fu, X.-Y., Deng, C.-X.
|
|
<strong>A Lys644Glu substitution in fibroblast growth factor receptor 3 (FGFR3) causes dwarfism in mice by activation of STATs and ink4 cell cycle inhibitors.</strong>
|
|
Hum. Molec. Genet. 8: 35-44, 1999.
|
|
|
|
|
|
[PubMed: 9887329]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/8.1.35]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, D., Liao, C., Ma, X., Li, Q., Tang, X.
|
|
<strong>Thanatophoric dysplasia type 2 with encephalocele during the second trimester.</strong>
|
|
Am. J. Med. Genet. 140A: 1476-1477, 2006.
|
|
|
|
|
|
[PubMed: 16752380]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31293]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lievens, P. M.-J., Liboi, E.
|
|
<strong>The thanatophoric dysplasia type II mutation hampers complete maturation of fibroblast growth factor receptor 3 (FGFR3), which activates signal transducer and activator of transcription 1 (STAT1) from the endoplasmic reticulum.</strong>
|
|
J. Biol. Chem. 278: 17344-17349, 2003.
|
|
|
|
|
|
[PubMed: 12624096]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M212710200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lin, T., Sandusky, S. B., Xue, H., Fishbein, K. W., Spencer, R. G., Rao, M. S., Francomano, C. A.
|
|
<strong>A central nervous system specific mouse model for thanatophoric dysplasia type II.</strong>
|
|
Hum. Molec. Genet. 12: 2863-2871, 2003.
|
|
|
|
|
|
[PubMed: 12966031]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg309]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Logie, A., Dunois-Larde, C., Rosty, C., Levrel, O., Blanche, M., Ribeiro, A., Gasc, J.-M., Jorcano, J., Werner, S., Sastre-Garau, X., Thiery, J. P., Radvanyi, F.
|
|
<strong>Activating mutations of the tyrosine kinase receptor FGFR3 are associated with benign skin tumors in mice and humans.</strong>
|
|
Hum. Molec. Genet. 14: 1153-1160, 2005.
|
|
|
|
|
|
[PubMed: 15772091]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi127]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lowry, R. B., Jabs, E. W., Graham, G. E., Gerritsen, J., Fleming, J.
|
|
<strong>Syndrome of coronal craniosynostosis, Klippel-Feil anomaly, and Sprengel shoulder with and without pro250arg mutation in the FGFR3 gene.</strong>
|
|
Am. J. Med. Genet. 104: 112-119, 2001.
|
|
|
|
|
|
[PubMed: 11746040]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.10049]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Makrythanasis, P., Temtamy, S., Aglan, M., Otaify, G. A., Hamamy, H., Antonarakis, S. E.
|
|
<strong>A novel homozygous mutation in FGFR3 causes tall stature, severe lateral tibial deviation, scoliosis, hearing impairment, camptodactyly, and arachnodactyly.</strong>
|
|
Hum. Mutat. 35: 959-963, 2014.
|
|
|
|
|
|
[PubMed: 24864036]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.22597]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mansour, S. L., Twigg, S. R. F., Freeland, R. M., Wall, S. A., Li, C., Wilkie, A. O. M.
|
|
<strong>Hearing loss in a mouse model of Muenke syndrome.</strong>
|
|
Hum. Molec. Genet. 18: 43-50, 2009.
|
|
|
|
|
|
[PubMed: 18818193]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddn311]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matsushita, T., Wilcox, W. R., Chan, Y. Y., Kawanami, A., Bukulmez, H., Balmes, G., Krejci, P., Mekikian, P. B., Otani, K., Yamaura, I., Warman, M. L., Givol, D., Murakami, S.
|
|
<strong>FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway.</strong>
|
|
Hum. Molec. Genet. 18: 227-240, 2009.
|
|
|
|
|
|
[PubMed: 18923003]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddn339]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McKusick, V. A., Kelly, T. E., Dorst, J. P.
|
|
<strong>Observations suggesting allelism of the achondroplasia and hypochondroplasia genes.</strong>
|
|
J. Med. Genet. 10: 11-16, 1973.
|
|
|
|
|
|
[PubMed: 4697848]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.10.1.11]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meyers, G. A., Orlow, S. J., Munro, I. R., Przylepa, K. A., Jabs, E. W.
|
|
<strong>Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans.</strong>
|
|
Nature Genet. 11: 462-464, 1995.
|
|
|
|
|
|
[PubMed: 7493034]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1295-462]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Moloney, D. M., Slaney, S. F., Oldridge, M., Wall, S. A., Sahlin, P., Stenman, G., Wilkie, A. O. M.
|
|
<strong>Exclusive paternal origin of new mutations in Apert syndrome.</strong>
|
|
Nature Genet. 13: 48-53, 1996.
|
|
|
|
|
|
[PubMed: 8673103]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0596-48]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Moloney, D. M., Wall, S. A., Ashworth, G. J., Oldridge, M., Glass, I. A., Francomano, C. A., Muenke, M., Wilkie, A. O. M.
|
|
<strong>Prevalence of pro250arg mutation of fibroblast growth factor receptor 3 in coronal craniosynostosis.</strong>
|
|
Lancet 349: 1059-1062, 1997.
|
|
|
|
|
|
[PubMed: 9107244]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(96)09082-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Monsonego-Ornan, E., Adar, R., Feferman, T., Segev, O., Yayon, A.
|
|
<strong>The transmembrane mutation G380R in fibroblast growth factor receptor 3 uncouples ligand-mediated receptor activation from down-regulation.</strong>
|
|
Molec. Cell. Biol. 20: 516-522, 2000.
|
|
|
|
|
|
[PubMed: 10611230]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.20.2.516-522.2000]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mortier, G., Nuytinck, L., Craen, M., Renard, J.-P., Leroy, J. G., De Paepe, A.
|
|
<strong>Clinical and radiographic features of a family with hypochondroplasia owing to a novel asn540ser mutation in the fibroblast growth factor receptor 3 gene.</strong>
|
|
J. Med. Genet. 37: 220-224, 2000.
|
|
|
|
|
|
[PubMed: 10777366]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.37.3.220]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Muenke, M., Gripp, K. W., McDonald-McGinn, D. M., Gaudenz, K., Whitaker, L. A., Bartlett, S. P., Markowitz, R. I., Robin, N. H., Nwokoro, N., Mulvihill, J. J., Losken, W., Mulliken, J. B., Guttmacher, A. E., Wilroy, R. S., Clarke, L. A., Hollway, G., Ades, L. C., Haan, E. A., Mulley, J. C., Cohen, M. M., Jr., Bellus, G. A., Francomano, C. A., Moloney, D. M., Wall, S. A., Wilkie, A. O. M., Zackai, E. H.
|
|
<strong>A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome.</strong>
|
|
Am. J. Hum. Genet. 60: 555-564, 1997.
|
|
|
|
|
|
[PubMed: 9042914]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Naski, M. C., Colvin, J. S., Coffin, J. D., Ornitz, D. M.
|
|
<strong>Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3.</strong>
|
|
Development 125: 4977-4988, 1998.
|
|
|
|
|
|
[PubMed: 9811582]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1242/dev.125.24.4977]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Naski, M. C., Wang, Q., Xu, J., Ornitz, D. M.
|
|
<strong>Graded activation of fibroblast growth factor receptor 3 by mutations causing achondroplasia and thanatophoric dysplasia.</strong>
|
|
Nature Genet. 13: 233-237, 1996.
|
|
|
|
|
|
[PubMed: 8640234]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0696-233]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Natacci, F., Baffico, M., Cavallari, U., Bedeschi, M. F., Mura, I., Paffoni, A., Setti, P. L., Baldi, M., Lalatta, F.
|
|
<strong>Germline mosaicism in achondroplasia detected in sperm DNA of the father of three affected sibs.</strong>
|
|
Am. J. Med. Genet. 146A: 784-786, 2008.
|
|
|
|
|
|
[PubMed: 18266238]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.32228]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nishimura, G., Fukushima, Y., Ohashi, H., Ikegawa, S.
|
|
<strong>Atypical radiological findings in achondroplasia with uncommon mutation of the fibroblast growth factor receptor-3 (FGFR-3) gene (gly to cys transition at codon 375). (Letter)</strong>
|
|
Am. J. Med. Genet. 59: 393-395, 1995.
|
|
|
|
|
|
[PubMed: 8599370]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1320590325]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nishimura, G., Takada, F.
|
|
<strong>Another observation of atypical radiologic findings in achondroplasia not due to a common mutation of the FGFR-3 gene: reply to Dr. Gorlin. (Letter)</strong>
|
|
Am. J. Med. Genet. 70: 203-205, 1997.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nowroozi, N., Raffioni, S., Wang, T., Apostol, B. L., Bradshaw, R. A., Thompson, L. M.
|
|
<strong>Sustained ERK1/2 but not STAT1 or 3 activation is required for thanatophoric dysplasia phenotypes in PC12 cells.</strong>
|
|
Hum. Molec. Genet. 14: 1529-1538, 2005.
|
|
|
|
|
|
[PubMed: 15843401]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi161]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pannier, S., Martinovic, J., Heuertz, S., Delezoide, A.-L., Munnich, A., Schibler, L., Serre, V., Legeai-Mallet, L.
|
|
<strong>Thanatophoric dysplasia caused by double missense FGFR3 mutations.</strong>
|
|
Am. J. Med. Genet. 149A: 1296-1301, 2009.
|
|
|
|
|
|
[PubMed: 19449430]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.32880]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Passos-Bueno, M. R., Wilcox, W. R., Jabs, E. W., Sertie, A. L., Alonso, L. G., Kitoh, H.
|
|
<strong>Clinical spectrum of fibroblast growth factor receptor mutations.</strong>
|
|
Hum. Mutat. 14: 115-125, 1999. Note: Erratum: Hum. Mutat. 17: 431 only, 2001.
|
|
|
|
|
|
[PubMed: 10425034]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1999)14:2<115::AID-HUMU3>3.0.CO;2-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Paumard-Hernandez, B., Berges-Soria, J., Barroso, E., Rivera-Pedroza, C. I., Perez-Carrizosa, V., Benito-Sanz, S., Lopez-Messa, E., Santos, F., Garcia-Recuero, I. I., Romance, A., Ballesta-Martinez, M. J., Lopez-Gonzalez, V., Campos-Barros, A., Cruz, J., Guillen-Navarro, E., Sanchez del Pozo, J., Lapunzina, P., Garcia-Minaur, S., Heath, K. E.
|
|
<strong>Expanding the mutation spectrum in 182 Spanish probands with craniosynostosis: identification and characterization of novel TCF12 variants.</strong>
|
|
Europ. J. Hum. Genet. 23: 907-914, 2015.
|
|
|
|
|
|
[PubMed: 25271085]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ejhg.2014.205]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Paznekas, W. A., Cunningham, M. L., Howard, T. D., Korf, B. R., Lipson, M. H., Grix, A. W., Feingold, M., Goldberg, R., Borochowitz, Z., Aleck, K., Mulliken, J., Yin, M., Jabs, E. W.
|
|
<strong>Genetic heterogeneity of Saethre-Chotzen syndrome, due to TWIST and FGFR mutations.</strong>
|
|
Am. J. Hum. Genet. 62: 1370-1380, 1998.
|
|
|
|
|
|
[PubMed: 9585583]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/301855]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Perez-Castro, A. V., Wilson, J., Altherr, M. R.
|
|
<strong>Genomic organization of the human fibroblast growth factor receptor 3 (FGFR3) gene and comparative sequence analysis with the mouse Fgfr3 gene.</strong>
|
|
Genomics 41: 10-16, 1997.
|
|
|
|
|
|
[PubMed: 9126476]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1997.4616]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pokharel, R. K., Alimsardjono, H., Takeshima, Y., Nakamura, H., Naritomi, K., Hirose, S., Onishi, S., Matsuo, M.
|
|
<strong>Japanese cases of type 1 thanatophoric dysplasia exclusively carry a C to T transition at nucleotide 742 of the fibroblast growth factor receptor 3 gene.</strong>
|
|
Biochem. Biophys. Res. Commun. 227: 236-239, 1996.
|
|
|
|
|
|
[PubMed: 8858131]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1996.1495]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Prinos, P., Costa, T., Sommer, A., Kilpatrick, M. W., Tsipouras, P.
|
|
<strong>A common FGFR3 gene mutation in hypochondroplasia.</strong>
|
|
Hum. Molec. Genet. 4: 2097-2101, 1995.
|
|
|
|
|
|
[PubMed: 8589686]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.11.2097]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Prinster, C., Carrera, P., Del Maschio, M., Weber, G., Maghnie, M., Vigone, M. C., Mora, S., Tonini, G., Rigon, F., Beluffi, G., Severi, F., Chiumello, G., Ferrari, M.
|
|
<strong>Comparison of clinical-radiological and molecular findings in hypochondroplasia.</strong>
|
|
Am. J. Med. Genet. 75: 109-112, 1998.
|
|
|
|
|
|
[PubMed: 9450868]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8628(19980106)75:1<109::aid-ajmg22>3.0.co;2-p]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ramaswami, U., Rumsby, G., Hindmarsh, P. C., Brook, C. G. D.
|
|
<strong>Genotype and phenotype in hypochondroplasia.</strong>
|
|
J. Pediat. 133: 99-102, 1998.
|
|
|
|
|
|
[PubMed: 9672519]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(98)70186-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rannan-Eliya, S. V., Taylor, I. B., de Heer, I. M., van den Ouweland, A. M. W., Wall, S. A., Wilkie, A. O. M.
|
|
<strong>Paternal origin of FGFR3 mutations in Muenke-type craniosynostosis.</strong>
|
|
Hum. Genet. 115: 200-207, 2004.
|
|
|
|
|
|
[PubMed: 15241680]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-004-1151-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rasmussen, T., Hudlebusch, H. R., Knudsen, L. M., Johnsen, H. E.
|
|
<strong>FGFR3 dysregulation in multiple myeloma: frequency and prognostic relevance.</strong>
|
|
Brit. J. Haemat. 117: 626-628, 2002.
|
|
|
|
|
|
[PubMed: 12028033]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1046/j.1365-2141.2002.03429.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reardon, W., Wilkes, D., Rutland, P., Pulleyn, L. J., Malcolm, S., Dean, J. C. S., Evans, R. D., Jones, B. M., Hayward, R., Hall, C. M., Nevin, N. C., Baraitser, M., Winter, R. M.
|
|
<strong>Craniosynostosis associated with FGFR3 pro250-to-arg mutation results in a range of clinical presentations including unisutural sporadic craniosynostosis.</strong>
|
|
J. Med. Genet. 34: 632-636, 1997.
|
|
|
|
|
|
[PubMed: 9279753]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.34.8.632]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Riley, B. M., Mansilla, M. A., Ma, J., Daack-Hirsch, S., Maher, B. S., Raffensperger, L. M., Russo, E. T., Vieira, A. R., Dode, C., Mohammadi, M., Marazita, M. L., Murray, J. C.
|
|
<strong>Impaired FGF signaling contributes to cleft lip and palate.</strong>
|
|
Proc. Nat. Acad. Sci. 104: 4512-4517, 2007.
|
|
|
|
|
|
[PubMed: 17360555]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0607956104]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Robin, N. H., Scott, J. A., Cohen, A. R., Goldstein, J. A.
|
|
<strong>Nonpenetrance in FGFR3-associated coronal synostosis syndrome. (Letter)</strong>
|
|
Am. J. Med. Genet. 80: 296-297, 1998.
|
|
|
|
|
|
[PubMed: 9843059]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rohmann, E., Brunner, H. G., Kayserili, H., Uyguner, O., Nurnberg, G., Lew, E. D., Dobbie, A., Eswarakumar, V. P., Uzumcu, A., Ulubil-Emeroglu, M., Leroy, J. G., Li, Y., and 9 others.
|
|
<strong>Mutations in different components of FGF signaling in LADD syndrome.</strong>
|
|
Nature Genet. 38: 414-417, 2006. Note: Erratum: Nature Genet. 38: 495 only, 2006.
|
|
|
|
|
|
[PubMed: 16501574]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1757]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Roscioli, T., Flanagan, S., Mortimore, R. J., Kumar, P., Weedon, D., Masel, J., Lewandowski, R., Hyland, V., Glass, I. A.
|
|
<strong>Premature calvarial synostosis and epidermal hyperplasia (Beare-Stevenson syndrome-like anomalies) resulting from a P250R missense mutation in the gene encoding fibroblast growth factor receptor 3.</strong>
|
|
Am. J. Med. Genet. 101: 187-194, 2001.
|
|
|
|
|
|
[PubMed: 11424131]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.1369]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rousseau, F., Bonaventure, J., Legeai-Mallet, L., Pelet, A., Rozet, J.-M., Maroteaux, P., Le Merrer, M., Munnich, A.
|
|
<strong>Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia.</strong>
|
|
Nature 371: 252-254, 1994.
|
|
|
|
|
|
[PubMed: 8078586]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/371252a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rousseau, F., El Ghouzzi, V., Delezoide, A. L., Legeai-Mallet, L., Le Merrer, M., Munnich, A., Bonaventure, J.
|
|
<strong>Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1).</strong>
|
|
Hum. Molec. Genet. 5: 509-512, 1996.
|
|
|
|
|
|
[PubMed: 8845844]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/5.4.509]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rousseau, F., Saugier, P., Le Merrer, M., Munnich, A., Delezoide, A.-L., Maroteaux, P., Bonaventure, J., Narcy, F., Sanak, M.
|
|
<strong>Stop codon FGFR3 mutations in thanatophoric dwarfism type 1.</strong>
|
|
Nature Genet. 10: 11-12, 1995.
|
|
|
|
|
|
[PubMed: 7647778]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0595-11]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rump, P., Letteboer, T. G. W., Gille, J. J. P., Torringa, M. J. L., Baerts, W., van Gestel, J. P. J., Verheij, J. B. G. M., van Essen, A. J.
|
|
<strong>Severe complications in a child with achondroplasia and two FGFR3 mutations on the same allele.</strong>
|
|
Am. J. Med. Genet. 140A: 284-290, 2006.
|
|
|
|
|
|
[PubMed: 16411219]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31084]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Saito, H., Sekizawa, A., Morimoto, T., Suzuki, M., Yanaihara, T.
|
|
<strong>Prenatal DNA diagnosis of a single-gene disorder from maternal plasma.</strong>
|
|
Lancet 356: 1170 only, 2000.
|
|
|
|
|
|
[PubMed: 11030304]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0140-6736(00)02767-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Salazar, L., Kashiwada, T., Krejci, P., Muchowski, P., Donoghue, D., Wilcox, W. R., Thompson, L. M.
|
|
<strong>A novel interaction between fibroblast growth factor receptor 3 and the p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation of ERK by p85 in multiple myeloma cells.</strong>
|
|
Hum. Molec. Genet. 18: 1951-1961, 2009.
|
|
|
|
|
|
[PubMed: 19286672]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp116]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sawai, H., Komori, S., Ida, A., Henmi, T., Bessho, T., Koyama, K.
|
|
<strong>Prenatal diagnosis of thanatophoric dysplasia by mutational analysis of the fibroblast growth factor receptor 3 gene and a proposed correction of previously published PCR results.</strong>
|
|
Prenatal Diag. 19: 21-24, 1999.
|
|
|
|
|
|
[PubMed: 10073901]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1097-0223(199901)19:1<21::aid-pd457>3.0.co;2-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scotet, E., Houssaint, E.
|
|
<strong>The choice between alternative IIIb and IIIc exons of the FGFR-3 gene is not strictly tissue-specific.</strong>
|
|
Biochim. Biophys. Acta 1264: 238-242, 1995.
|
|
|
|
|
|
[PubMed: 7495869]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0167-4781(95)00156-b]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shiang, R., Thompson, L. M., Zhu, Y.-Z., Church, D. M., Fielder, T. J., Bocian, M., Winokur, S. T., Wasmuth, J. J.
|
|
<strong>Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia.</strong>
|
|
Cell 78: 335-342, 1994.
|
|
|
|
|
|
[PubMed: 7913883]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(94)90302-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shimizu, A., Tada, K., Shukunami, C., Hiraki, Y., Kurokawa, T., Magane, N., Kurokawa-Seo, M.
|
|
<strong>A novel alternatively spliced fibroblast growth factor receptor 3 isoform lacking the acid box domain is expressed during chondrogenic differentiation of ATDC5 cells.</strong>
|
|
J. Biol. Chem. 276: 11031-11040, 2001.
|
|
|
|
|
|
[PubMed: 11134040]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M003535200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shimizu, A., Takashima, Y., Kurokawa-Seo, M.
|
|
<strong>FGFR3 isoforms have distinct functions in the regulation of growth and cell morphology.</strong>
|
|
Biochem. Biophys. Res. Commun. 290: 113-120, 2002.
|
|
|
|
|
|
[PubMed: 11779141]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.2001.6190]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sibley, K., Cuthbert-Heavens, D., Knowles, M. A.
|
|
<strong>Loss of heterozygosity at 4p16.3 and mutation of FGFR3 in transitional cell carcinoma.</strong>
|
|
Oncogene 20: 686-691, 2001.
|
|
|
|
|
|
[PubMed: 11314002]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.onc.1204110]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Singh, D., Chan, J. M., Zoppoli, P., Niola, F., Sullivan, R., Castano, A., Liu, E. M., Reichel, J., Porrati, P., Pellegatta, S., Qiu, K., Gao, Z., and 12 others.
|
|
<strong>Transforming fusions of FGFR and TACC genes in human glioblastoma.</strong>
|
|
Science 337: 1231-1235, 2012.
|
|
|
|
|
|
[PubMed: 22837387]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1220834]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sobetzko, D., Braga, S., Rudeberg, A., Superti-Furga, A.
|
|
<strong>Achondroplasia with the FGFR3 1138g-a (G380R) mutation in two sibs sharing a 4p haplotype derived from their unaffected father. (Letter)</strong>
|
|
J. Med. Genet. 37: 958-959, 2000.
|
|
|
|
|
|
[PubMed: 11186940]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.37.12.958]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Spranger, J.
|
|
<strong>Bone dysplasia 'families'.</strong>
|
|
Path. Immunopath. Res. 7: 76-80, 1988.
|
|
|
|
|
|
[PubMed: 3222210]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000157098]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Su, N., Sun, Q., Li, C., Lu, X., Qi, H., Chen, S., Yang, J., Du, X., Zhao, L., He, Q., Jin, M., Shen, Y., Chen, D., Chen, L.
|
|
<strong>Gain-of-function mutation in FGFR3 in mice leads to decreased bone mass by affecting both osteoblastogenesis and osteoclastogenesis.</strong>
|
|
Hum. Molec. Genet. 19: 1199-1210, 2010.
|
|
|
|
|
|
[PubMed: 20053668]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp590]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Su, W.-C. S., Kitagawa, M., Xue, N., Xie, B., Garofalo, S., Cho, J., Deng, C., Horton, W. A., Fu, X.-Y.
|
|
<strong>Activation of Stat1 by mutant fibroblast growth-factor receptor in thanatophoric dysplasia type II dwarfism.</strong>
|
|
Nature 386: 288-292, 1997.
|
|
|
|
|
|
[PubMed: 9069288]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/386288a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Su, Y.-N., Lee, C.-N., Chien, S.-C., Hung, C.-C., Chien, Y.-H., Chen, C.-A.
|
|
<strong>Rapid detection of FGFR3 gene mutation in achondroplasia by DHPLC system-coupling heteroduplex and fluorescence-enhanced primer-extension analysis.</strong>
|
|
J. Hum. Genet. 49: 399-403, 2004.
|
|
|
|
|
|
[PubMed: 15221641]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10038-004-0165-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Superti-Furga, A., Eich, G., Bucher, H. U., Wisser, J., Giedion, A., Gitzelmann, R., Steinmann, B.
|
|
<strong>A glycine 375-to-cysteine substitution in the transmembrane domain of the fibroblast growth factor receptor-3 in a newborn with achondroplasia.</strong>
|
|
Europ. J. Pediat. 154: 215-219, 1995.
|
|
|
|
|
|
[PubMed: 7758520]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF01954274]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Szabo, J., Bellus, G. A., Kaitila, I., Francomano, C. A.
|
|
<strong>Fibroblast growth factor receptor 3 (FGFR3) mutations in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 59 (suppl.): A287 only, 1996.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Talebi, F., Ghanbari Mardasi, F., Mohammadi Asl, J., Bavarsad, A. H., Tizno, S.
|
|
<strong>Identification of a novel missence (sic) mutation in FGFR3 gene in an Iranian family with LADD syndrome by next-generation sequencing.</strong>
|
|
Int. J. Pediat. Otorhinolaryng. 97: 192-196, 2017.
|
|
|
|
|
|
[PubMed: 28483234]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ijporl.2017.04.016]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tavormina, P. L., Bellus, G. A., Webster, M. K., Bamshad, M. J., Fraley, A. E., McIntosh, I., Szabo, J., Jiang, W., Jabs, E. W., Wilcox, W. R., Wasmuth, J. J., Donoghue, D. J., Thompson, L. M., Francomano, C. A.
|
|
<strong>A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a lys650-to-met mutation in the fibroblast growth factor receptor 3 gene.</strong>
|
|
Am. J. Hum. Genet. 64: 722-731, 1999.
|
|
|
|
|
|
[PubMed: 10053006]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302275]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tavormina, P. L., Rimoin, D. L., Cohn, D. H., Zhu, Y.-Z., Shiang, R., Wasmuth, J. J.
|
|
<strong>Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type I.</strong>
|
|
Hum. Molec. Genet. 4: 2175-2177, 1995.
|
|
|
|
|
|
[PubMed: 8589699]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.11.2175]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tavormina, P. L., Shiang, R., Thompson, L. M., Zhu, Y.-Z., Wilkin, D. J., Lachman, R. S., Wilcox, W. R., Rimoin, D. L., Cohn, D. H., Wasmuth, J. J.
|
|
<strong>Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3.</strong>
|
|
Nature Genet. 9: 321-328, 1995.
|
|
|
|
|
|
[PubMed: 7773297]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0395-321]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thauvin-Robinet, C., Faivre, L., Lewin, P., De Monleon, J.-V., Francois, C., Huet, F., Couailler, J.-F., Campos-Xavier, A. B., Bonaventure, J., Le Merrer, M.
|
|
<strong>Hypochondroplasia and stature within normal limits: another family with an asn540-to-ser mutation in the fibroblast growth factor receptor 3 gene. (Letter)</strong>
|
|
Am. J. Med. Genet. 119A: 81-84, 2003.
|
|
|
|
|
|
[PubMed: 12707965]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.10238]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thompson, L. M., Plummer, S., Schalling, M., Altherr, M. R., Gusella, J. F., Housman, D. E., Wasmuth, J. J.
|
|
<strong>A gene encoding a fibroblast growth factor receptor isolated from the Huntington disease gene region of human chromosome 4.</strong>
|
|
Genomics 11: 1133-1142, 1991.
|
|
|
|
|
|
[PubMed: 1664411]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(91)90041-c]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Toydemir, R. M., Brassington, A. E., Bayrak-Toydemir, P., Krakowiak, P. A., Jorde, L. B., Whitby, F. G., Longo, N., Viskochil, D. H., Carey, J. C., Bamshad, M. J.
|
|
<strong>A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome.</strong>
|
|
Am. J. Hum. Genet. 79: 935-941, 2006.
|
|
|
|
|
|
[PubMed: 17033969]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/508433]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tsai, F.-J., Tsai, C.-H., Chang, J.-G., Wu, J.-Y.
|
|
<strong>Mutations in the fibroblast growth factor receptor 3 (FGFR3) cause achondroplasia, hypochondroplasia, and thanatophoric dysplasia: Taiwanese data. (Letter)</strong>
|
|
Am. J. Med. Genet. 86: 300-301, 1999.
|
|
|
|
|
|
[PubMed: 10482885]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tsai, F.-J., Wu, J.-Y., Tsai, C.-H., Chang, J.-G.
|
|
<strong>Identification of a common N540K mutation in 8/18 Taiwanese hypochondroplasia patients: further evidence for genetic heterogeneity. (Letter)</strong>
|
|
Clin. Genet. 55: 279-280, 1999.
|
|
|
|
|
|
[PubMed: 10361991]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.1999.550412.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Valverde-Franco, G., Liu, H., Davidson, D., Chai, S., Valderrama-Carvajal, H., Goltzman, D., Ornitz, D. M., Henderson, J. E.
|
|
<strong>Defective bone mineralization and osteopenia in young adult FGFR3 -/- mice.</strong>
|
|
Hum. Molec. Genet. 13: 271-284, 2004.
|
|
|
|
|
|
[PubMed: 14681299]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddh034]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van Esch, H., Fryns, J. P.
|
|
<strong>Acanthosis nigricans in a boy with achondroplasia due to the classical gly380arg mutation in FGFR3.</strong>
|
|
Genet. Counsel. 15: 375-377, 2004.
|
|
|
|
|
|
[PubMed: 15517832]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
von Gernet, S., Schuffenhauer, S., Golla, A., Lichtner, P., Balg, S., Muhlbauer, W., Murken, J., Fairley, J., Meitinger, T.
|
|
<strong>Craniosynostosis suggestive of Saethre-Chotzen syndrome: clinical description of a large kindred and exclusion of candidate regions on 7p.</strong>
|
|
Am. J. Med. Genet. 63: 177-184, 1996.
|
|
|
|
|
|
[PubMed: 8723106]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1096-8628(19960503)63:1<177::AID-AJMG31>3.0.CO;2-J]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, H., Sun, Y., Wu, W., Wei, X., Lan, Z., Xie, J.
|
|
<strong>A novel missense mutation of FGFR3 in a Chinese female and her fetus with hypochondroplasia by next-generation sequencing.</strong>
|
|
Clin. Chim. Acta 423: 62-65, 2013.
|
|
|
|
|
|
[PubMed: 23726269]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cca.2013.04.015]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wilcox, W. R., Tavormina, P. L., Krakow, D., Kitoh, H., Lachman, R. S., Wasmuth, J. J., Thompson, L. M., Rimoin, D. L.
|
|
<strong>Molecular, radiologic, and histopathologic correlations in thanatophoric dysplasia.</strong>
|
|
Am. J. Med. Genet. 78: 274-281, 1998.
|
|
|
|
|
|
[PubMed: 9677066]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8628(19980707)78:3<274::aid-ajmg14>3.0.co;2-c]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wilkie, A. O. M., Bochukova, E. G., Hansen, R. M. S., Taylor, I. B., Rannan-Eliya, S. V., Byren, J. C., Wall, S. A., Ramos, L., Venancio, M., Hurst, J. A., O'Rourke, A. W., Williams, L. J., Seller, A., Lester, T.
|
|
<strong>Clinical dividends from the molecular genetic diagnosis of craniosynostosis.</strong>
|
|
Am. J. Med. Genet. 143A: 1941-1949, 2007. Note: Republication with correction of an article originally published in Am. J. Med. Genet. 140A: 2631-2639, 2006.
|
|
|
|
|
|
[PubMed: 17621648]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.31905]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wilkie, A. O. M., Byren, J. C., Hurst, J. A., Jayamohan, J., Johnson, D., Knight, S. J. L., Lester, T., Richards, P. G., Twigg, S. R. F., Wall, S. A.
|
|
<strong>Prevalence and complications of single-gene and chromosomal disorders in craniosynostosis.</strong>
|
|
Pediatrics 126: e391-e400, 2010.
|
|
|
|
|
|
[PubMed: 20643727]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1542/peds.2009-3491]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wilkie, A. O. M.
|
|
<strong>Craniosynostosis: genes and mechanisms.</strong>
|
|
Hum. Molec. Genet. 6: 1647-1656, 1997.
|
|
|
|
|
|
[PubMed: 9300656]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/6.10.1647]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wyrobek, A. J., Eskenazi, B., Young, S., Arnheim, N., Tiemann-Boege, I., Jabs, E. W., Glaser, R. L., Pearson, F. S., Evenson, D.
|
|
<strong>Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 9601-9606, 2006.
|
|
|
|
|
|
[PubMed: 16766665]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0506468103]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yamashita, A., Morioka, M., Kishi, H., Kimura, T., Yahara, Y., Okada, M., Fujita, K., Sawai, H., Ikegawa, S., Tsumaki, N.
|
|
<strong>Statin treatment rescues FGFR3 skeletal dysplasia phenotypes.</strong>
|
|
Nature 513: 507-511, 2014.
|
|
|
|
|
|
[PubMed: 25231866]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature13775]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yasoda, A., Komatsu, Y., Chusho, H., Miyazawa, T., Ozasa, A., Miura, M., Kurihara, T., Rogi, T., Tanaka, S., Suda, M., Tamura, N., Ogawa, Y., Nakao, K.
|
|
<strong>Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway.</strong>
|
|
Nature Med. 10: 80-86, 2004.
|
|
|
|
|
|
[PubMed: 14702637]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm971]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zankl, A., Elakis, G., Susman, R. D., Inglis, G., Gardener, G., Buckley, M. F., Roscioli, T.
|
|
<strong>Prenatal and postnatal presentation of severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) due to the FGFR3 lys650met mutation.</strong>
|
|
Am. J. Med. Genet. 146A: 212-218, 2008.
|
|
|
|
|
|
[PubMed: 18076102]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.32085]
|
|
|
|
|
|
</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">
|
|
Carol A. Bocchini - updated : 01/07/2023<br>Marla J. F. O'Neill - updated : 01/25/2022<br>Ada Hamosh - updated : 09/10/2018<br>Carol A. Bocchini - updated : 06/05/2018<br>Patricia A. Hartz - updated : 6/30/2015<br>Cassandra L. Kniffin - updated : 10/20/2014<br>Ada Hamosh - updated : 10/9/2014<br>Paul J. Converse - updated : 2/7/2014<br>Ada Hamosh - updated : 10/31/2012<br>Patricia A. Hartz - updated : 2/13/2012<br>Cassandra L. Kniffin - updated : 1/4/2012<br>George E. Tiller - updated : 11/14/2011<br>Patricia A. Hartz - updated : 7/22/2011<br>Cassandra L. Kniffin - updated : 11/8/2010<br>George E. Tiller - updated : 3/2/2010<br>Ada Hamosh - updated : 2/16/2010<br>George E. Tiller - updated : 10/23/2009<br>Nara Sobreira - updated : 7/14/2009<br>George E. Tiller - updated : 4/16/2009<br>Cassandra L. Kniffin - updated : 3/4/2009<br>Cassandra L. Kniffin - updated : 1/5/2009<br>Cassandra L. Kniffin - updated : 10/23/2008<br>Cassandra L. Kniffin - updated : 8/22/2008<br>Cassandra L. Kniffin - updated : 7/29/2008<br>George E. Tiller - updated : 6/11/2008<br>Cassandra L. Kniffin - updated : 5/30/2008<br>George E. Tiller - updated : 5/19/2008<br>Marla J. F. O'Neill - updated : 4/30/2008<br>Marla J. F. O'Neill - updated : 4/30/2007<br>Marla J. F. O'Neill - updated : 4/13/2007<br>Cassandra L. Kniffin - updated : 3/23/2007<br>Marla J. F. O'Neill - updated : 3/8/2007<br>Marla J. F. O'Neill - updated : 3/2/2007<br>Victor A. McKusick - updated : 10/10/2006<br>Cassandra L. Kniffin - updated : 7/11/2006<br>Victor A. McKusick - updated : 4/27/2006<br>George E. Tiller - updated : 2/17/2006<br>Cassandra L. Kniffin - updated : 2/8/2006<br>George E. Tiller - updated : 2/7/2006<br>Marla J. F. O'Neill - updated : 4/18/2005<br>Victor A. McKusick - updated : 1/12/2005<br>Victor A. McKusick - updated : 11/29/2004<br>Victor A. McKusick - updated : 9/27/2004<br>Marla J. F. O'Neill - updated : 6/30/2004<br>Victor A. McKusick - updated : 4/9/2004<br>Victor A. McKusick - updated : 1/22/2004<br>Victor A. McKusick - updated : 7/2/2003<br>Victor A. McKusick - updated : 6/27/2003<br>Victor A. McKusick - updated : 5/15/2003<br>Victor A. McKusick - updated : 2/12/2003<br>Victor A. McKusick - updated : 9/12/2002<br>Patricia A. Hartz - reorganized : 8/7/2002<br>Patricia A. Hartz - updated : 8/7/2002<br>Victor A. McKusick - updated : 2/26/2002<br>Sonja A. Rasmussen - updated : 12/6/2001<br>Victor A. McKusick - updated : 12/4/2001<br>George E. Tiller - updated : 11/7/2001<br>Victor A. McKusick - updated : 10/11/2001<br>Victor A. McKusick - updated : 7/30/2001<br>Victor A. McKusick - updated : 6/26/2001<br>George E. Tiller - updated : 5/17/2001<br>Victor A. McKusick - updated : 4/9/2001<br>Victor A. McKusick - updated : 2/2/2001<br>Michael J. Wright - updated : 1/11/2001<br>Victor A. McKusick - updated : 12/13/2000<br>George E. Tiller - updated : 9/15/2000<br>Victor A. McKusick - updated : 3/15/2000<br>Victor A. McKusick - updated : 1/12/2000<br>Victor A. McKusick - updated : 12/20/1999<br>Victor A. McKusick - updated : 10/21/1999<br>Ada Hamosh - updated : 9/21/1999<br>Victor A. McKusick - updated : 6/29/1999<br>Victor A. McKusick - updated : 6/17/1999<br>Victor A. McKusick - updated : 5/11/1999<br>Victor A. McKusick - updated : 4/21/1999<br>Victor A. McKusick - updated : 4/14/1999<br>Victor A. McKusick - updated : 3/12/1999<br>Victor A. McKusick - updated : 3/9/1999<br>Victor A. McKusick - updated : 2/19/1999<br>Michael J. Wright - updated : 2/12/1999<br>Victor A. McKusick - updated : 1/26/1999<br>Victor A. McKusick - updated : 1/23/1999<br>Victor A. McKusick - updated : 1/13/1999<br>Victor A. McKusick - updated : 1/5/1999<br>Victor A. McKusick - updated : 12/30/1998<br>Victor A. McKusick - updated : 9/2/1998<br>Victor A. McKusick - updated : 8/26/1998<br>Victor A. McKusick - updated : 8/17/1998<br>Victor A. McKusick - updated : 7/27/1998<br>Victor A. McKusick - updated : 7/15/1998<br>Victor A. McKusick - updated : 7/1/1998<br>Victor A. McKusick - updated : 6/23/1998<br>Victor A. McKusick - updated : 6/12/1998<br>Rebekah S. Rasooly - updated : 5/7/1998<br>Victor A. McKusick - updated : 3/2/1998<br>Victor A. McKusick - updated : 2/11/1998<br>Victor A. McKusick - updated : 1/12/1998<br>Victor A. McKusick - updated : 7/3/1997<br>Victor A. McKusick - updated : 5/28/1997<br>Victor A. McKusick - updated : 3/12/1997<br>Moyra Smith - updated : 5/6/1996<br>Moyra Smith - edited : 5/2/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 7/9/1991
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 12/20/2023<br>carol : 01/10/2023<br>carol : 01/09/2023<br>carol : 01/07/2023<br>carol : 11/02/2022<br>carol : 11/01/2022<br>carol : 01/25/2022<br>carol : 06/11/2019<br>alopez : 09/10/2018<br>carol : 06/06/2018<br>carol : 06/05/2018<br>carol : 10/20/2017<br>carol : 10/19/2017<br>carol : 10/18/2017<br>joanna : 07/20/2016<br>joanna : 07/19/2016<br>joanna : 07/19/2016<br>joanna : 06/30/2016<br>carol : 4/26/2016<br>mgross : 8/26/2015<br>carol : 7/24/2015<br>mcolton : 6/30/2015<br>carol : 10/21/2014<br>ckniffin : 10/20/2014<br>alopez : 10/9/2014<br>carol : 9/22/2014<br>carol : 7/28/2014<br>carol : 2/21/2014<br>carol : 2/11/2014<br>mgross : 2/10/2014<br>mcolton : 2/7/2014<br>mcolton : 2/5/2014<br>mcolton : 2/5/2014<br>terry : 4/1/2013<br>alopez : 11/5/2012<br>terry : 10/31/2012<br>ckniffin : 7/25/2012<br>terry : 6/7/2012<br>carol : 6/5/2012<br>alopez : 4/12/2012<br>mgross : 2/24/2012<br>mgross : 2/24/2012<br>terry : 2/13/2012<br>carol : 2/2/2012<br>joanna : 1/31/2012<br>ckniffin : 1/4/2012<br>ckniffin : 1/4/2012<br>carol : 11/15/2011<br>terry : 11/14/2011<br>mgross : 8/5/2011<br>terry : 7/22/2011<br>carol : 5/23/2011<br>ckniffin : 1/3/2011<br>ckniffin : 12/28/2010<br>carol : 12/2/2010<br>carol : 11/15/2010<br>wwang : 11/12/2010<br>ckniffin : 11/8/2010<br>terry : 11/3/2010<br>terry : 9/8/2010<br>carol : 8/18/2010<br>wwang : 3/2/2010<br>alopez : 3/2/2010<br>terry : 2/16/2010<br>wwang : 11/2/2009<br>terry : 10/23/2009<br>wwang : 9/15/2009<br>carol : 7/14/2009<br>wwang : 4/20/2009<br>alopez : 4/16/2009<br>carol : 4/3/2009<br>wwang : 3/16/2009<br>ckniffin : 3/4/2009<br>wwang : 1/8/2009<br>ckniffin : 1/5/2009<br>wwang : 10/23/2008<br>carol : 9/4/2008<br>ckniffin : 8/22/2008<br>carol : 8/7/2008<br>ckniffin : 7/29/2008<br>wwang : 6/11/2008<br>wwang : 6/5/2008<br>ckniffin : 5/30/2008<br>ckniffin : 5/30/2008<br>wwang : 5/21/2008<br>terry : 5/19/2008<br>wwang : 5/9/2008<br>terry : 4/30/2008<br>wwang : 6/13/2007<br>wwang : 4/30/2007<br>wwang : 4/20/2007<br>terry : 4/13/2007<br>wwang : 4/11/2007<br>ckniffin : 3/23/2007<br>wwang : 3/9/2007<br>wwang : 3/9/2007<br>terry : 3/8/2007<br>wwang : 3/6/2007<br>terry : 3/2/2007<br>carol : 10/10/2006<br>carol : 10/10/2006<br>terry : 10/10/2006<br>wwang : 7/31/2006<br>ckniffin : 7/11/2006<br>alopez : 5/1/2006<br>terry : 4/27/2006<br>wwang : 4/7/2006<br>terry : 4/6/2006<br>wwang : 3/9/2006<br>wwang : 3/7/2006<br>terry : 2/17/2006<br>terry : 2/17/2006<br>wwang : 2/13/2006<br>ckniffin : 2/8/2006<br>wwang : 2/7/2006<br>carol : 4/26/2005<br>wwang : 4/19/2005<br>terry : 4/18/2005<br>wwang : 1/20/2005<br>wwang : 1/19/2005<br>wwang : 1/13/2005<br>terry : 1/12/2005<br>alopez : 11/29/2004<br>terry : 11/29/2004<br>carol : 9/28/2004<br>terry : 9/27/2004<br>carol : 7/1/2004<br>terry : 6/30/2004<br>tkritzer : 4/14/2004<br>terry : 4/9/2004<br>alopez : 1/23/2004<br>terry : 1/22/2004<br>carol : 7/8/2003<br>terry : 7/2/2003<br>terry : 6/27/2003<br>tkritzer : 5/20/2003<br>terry : 5/15/2003<br>carol : 2/27/2003<br>tkritzer : 2/24/2003<br>terry : 2/12/2003<br>carol : 9/19/2002<br>tkritzer : 9/12/2002<br>tkritzer : 9/12/2002<br>mgross : 8/12/2002<br>mgross : 8/7/2002<br>mgross : 8/7/2002<br>mgross : 8/7/2002<br>mgross : 3/6/2002<br>terry : 2/26/2002<br>mcapotos : 12/17/2001<br>mcapotos : 12/17/2001<br>carol : 12/10/2001<br>mcapotos : 12/6/2001<br>mcapotos : 12/4/2001<br>cwells : 11/20/2001<br>cwells : 11/7/2001<br>carol : 11/5/2001<br>mcapotos : 10/31/2001<br>terry : 10/11/2001<br>cwells : 8/10/2001<br>cwells : 8/8/2001<br>cwells : 8/1/2001<br>terry : 7/30/2001<br>mcapotos : 6/29/2001<br>mcapotos : 6/28/2001<br>terry : 6/26/2001<br>cwells : 5/24/2001<br>cwells : 5/17/2001<br>cwells : 5/17/2001<br>mcapotos : 4/11/2001<br>mcapotos : 4/9/2001<br>terry : 4/9/2001<br>mcapotos : 2/13/2001<br>cwells : 2/8/2001<br>terry : 2/2/2001<br>alopez : 1/11/2001<br>mcapotos : 1/9/2001<br>mcapotos : 12/28/2000<br>terry : 12/13/2000<br>alopez : 9/15/2000<br>mcapotos : 4/6/2000<br>mcapotos : 4/6/2000<br>mcapotos : 4/5/2000<br>terry : 3/15/2000<br>mgross : 1/31/2000<br>terry : 1/12/2000<br>carol : 1/5/2000<br>mcapotos : 1/5/2000<br>mcapotos : 12/29/1999<br>terry : 12/20/1999<br>alopez : 10/27/1999<br>carol : 10/25/1999<br>terry : 10/21/1999<br>carol : 9/21/1999<br>carol : 6/29/1999<br>jlewis : 6/23/1999<br>terry : 6/17/1999<br>mgross : 5/17/1999<br>mgross : 5/13/1999<br>terry : 5/11/1999<br>carol : 4/23/1999<br>terry : 4/21/1999<br>mgross : 4/20/1999<br>mgross : 4/19/1999<br>terry : 4/14/1999<br>mgross : 3/17/1999<br>carol : 3/16/1999<br>terry : 3/12/1999<br>terry : 3/9/1999<br>mgross : 3/3/1999<br>mgross : 3/1/1999<br>mgross : 3/1/1999<br>mgross : 2/24/1999<br>mgross : 2/19/1999<br>terry : 2/12/1999<br>terry : 2/12/1999<br>carol : 1/26/1999<br>carol : 1/23/1999<br>carol : 1/13/1999<br>terry : 1/13/1999<br>carol : 1/6/1999<br>terry : 1/5/1999<br>carol : 1/4/1999<br>terry : 12/30/1998<br>carol : 9/8/1998<br>alopez : 9/2/1998<br>carol : 8/27/1998<br>terry : 8/26/1998<br>carol : 8/18/1998<br>terry : 8/17/1998<br>terry : 7/27/1998<br>carol : 7/23/1998<br>carol : 7/16/1998<br>carol : 7/15/1998<br>carol : 7/14/1998<br>dholmes : 7/13/1998<br>terry : 7/1/1998<br>carol : 7/1/1998<br>terry : 6/23/1998<br>carol : 6/12/1998<br>dholmes : 6/12/1998<br>terry : 5/29/1998<br>carol : 5/26/1998<br>psherman : 5/7/1998<br>psherman : 4/15/1998<br>dholmes : 3/9/1998<br>alopez : 3/3/1998<br>alopez : 3/3/1998<br>dholmes : 3/2/1998<br>dholmes : 3/2/1998<br>alopez : 2/11/1998<br>dholmes : 2/10/1998<br>dholmes : 2/6/1998<br>alopez : 1/12/1998<br>dholmes : 1/6/1998<br>alopez : 10/27/1997<br>terry : 10/23/1997<br>alopez : 7/29/1997<br>alopez : 7/29/1997<br>mark : 7/7/1997<br>alopez : 7/7/1997<br>terry : 7/3/1997<br>alopez : 6/26/1997<br>jenny : 6/5/1997<br>terry : 5/28/1997<br>terry : 3/31/1997<br>terry : 3/12/1997<br>terry : 3/6/1997<br>mark : 12/27/1996<br>terry : 12/12/1996<br>terry : 12/4/1996<br>terry : 11/25/1996<br>terry : 11/22/1996<br>mark : 10/8/1996<br>mark : 10/8/1996<br>mark : 10/5/1996<br>terry : 10/2/1996<br>mark : 5/30/1996<br>terry : 5/29/1996<br>carol : 5/16/1996<br>mark : 5/6/1996<br>mark : 5/6/1996<br>mark : 5/6/1996<br>mark : 5/6/1996<br>mark : 5/3/1996<br>mark : 5/2/1996<br>joanna : 4/26/1996<br>carol : 4/16/1996<br>mark : 4/9/1996<br>terry : 4/5/1996<br>mark : 2/26/1996<br>terry : 2/6/1996<br>mark : 1/18/1996<br>terry : 1/16/1996<br>mark : 12/11/1995<br>mark : 12/6/1995<br>mark : 11/17/1995<br>terry : 2/24/1995<br>carol : 1/18/1995<br>jason : 7/28/1994<br>supermim : 3/16/1992<br>carol : 12/5/1991
|
|
</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>
|
|
|
|
|