5378 lines
469 KiB
Text
5378 lines
469 KiB
Text
|
|
|
|
|
|
|
|
|
|
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
|
|
|
|
<head>
|
|
|
|
|
|
|
|
<!--
|
|
################################# CRAWLER WARNING #################################
|
|
|
|
- The terms of service and the robots.txt file disallows crawling of this site,
|
|
please see https://omim.org/help/agreement for more information.
|
|
|
|
- A number of data files are available for download at https://omim.org/downloads.
|
|
|
|
- We have an API which you can learn about at https://omim.org/help/api and register
|
|
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
|
|
|
|
- You should feel free to contact us at https://omim.org/contact to figure out the best
|
|
approach to getting the data you need for your work.
|
|
|
|
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
|
|
|
|
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
|
|
DISTRIBUTED CRAWLS OF THIS SITE.
|
|
|
|
################################# CRAWLER WARNING #################################
|
|
-->
|
|
|
|
|
|
|
|
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
|
|
<meta http-equiv="cache-control" content="no-cache" />
|
|
<meta http-equiv="pragma" content="no-cache" />
|
|
<meta name="robots" content="index, follow" />
|
|
|
|
|
|
<meta name="viewport" content="width=device-width, initial-scale=1" />
|
|
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
|
|
|
|
|
|
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
|
|
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
|
|
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
|
|
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
|
|
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
|
|
contain copious links to other genetics resources." />
|
|
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
|
|
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
|
|
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
|
|
<meta name="theme-color" content="#333333" />
|
|
<link rel="icon" href="/static/omim/favicon.png" />
|
|
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
|
|
<link rel="manifest" href="/static/omim/manifest.json" />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script id='mimBrowserCapability'>
|
|
function _0x5069(){const _0x4b1387=['91sZIeLc','mimBrowserCapability','15627zshTnf','710004yxXedd','34LxqNYj','match','disconnect','1755955rnzTod','observe','1206216ZRfBWB','575728fqgsYy','webdriver','documentElement','close','open','3086704utbakv','7984143PpiTpt'];_0x5069=function(){return _0x4b1387;};return _0x5069();}function _0xe429(_0x472ead,_0x43eb70){const _0x506916=_0x5069();return _0xe429=function(_0xe42949,_0x1aaefc){_0xe42949=_0xe42949-0x1a9;let _0xe6add8=_0x506916[_0xe42949];return _0xe6add8;},_0xe429(_0x472ead,_0x43eb70);}(function(_0x337daa,_0x401915){const _0x293f03=_0xe429,_0x5811dd=_0x337daa();while(!![]){try{const _0x3dc3a3=parseInt(_0x293f03(0x1b4))/0x1*(-parseInt(_0x293f03(0x1b6))/0x2)+parseInt(_0x293f03(0x1b5))/0x3+parseInt(_0x293f03(0x1b0))/0x4+-parseInt(_0x293f03(0x1b9))/0x5+parseInt(_0x293f03(0x1aa))/0x6+-parseInt(_0x293f03(0x1b2))/0x7*(parseInt(_0x293f03(0x1ab))/0x8)+parseInt(_0x293f03(0x1b1))/0x9;if(_0x3dc3a3===_0x401915)break;else _0x5811dd['push'](_0x5811dd['shift']());}catch(_0x4dd27b){_0x5811dd['push'](_0x5811dd['shift']());}}}(_0x5069,0x84d63),(function(){const _0x9e4c5f=_0xe429,_0x363a26=new MutationObserver(function(){const _0x458b09=_0xe429;if(document!==null){let _0x2f0621=![];navigator[_0x458b09(0x1ac)]!==![]&&(_0x2f0621=!![]);for(const _0x427dda in window){_0x427dda[_0x458b09(0x1b7)](/cdc_[a-z0-9]/ig)&&(_0x2f0621=!![]);}_0x2f0621===!![]?document[_0x458b09(0x1af)]()[_0x458b09(0x1ae)]():(_0x363a26[_0x458b09(0x1b8)](),document['getElementById'](_0x458b09(0x1b3))['remove']());}});_0x363a26[_0x9e4c5f(0x1a9)](document[_0x9e4c5f(0x1ad)],{'childList':!![]});}()));
|
|
</script>
|
|
|
|
|
|
|
|
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
|
|
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
|
|
|
|
<link rel="preconnect" href="https://www.googletagmanager.com" />
|
|
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
|
|
<script>
|
|
window.dataLayer = window.dataLayer || [];
|
|
function gtag(){window.dataLayer.push(arguments);}
|
|
gtag("js", new Date());
|
|
gtag("config", "G-HMPSQC23JJ");
|
|
</script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
|
|
|
|
|
|
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
|
|
|
|
|
|
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimBootstrapDeviceSize">
|
|
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
|
|
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
|
|
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
|
|
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
|
|
</div>
|
|
|
|
|
|
|
|
<title>
|
|
|
|
Entry
|
|
|
|
- *605516 - CADHERIN 23; CDH23
|
|
|
|
|
|
- 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=605516"><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">*605516</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="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#biochemicalFeatures">Biochemical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</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/605516">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=ENSG00000107736;t=ENST00000224721" 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=64072" 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=605516" 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=ENSG00000107736;t=ENST00000224721" 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_001171930,NM_001171931,NM_001171932,NM_001171933,NM_001171934,NM_001171935,NM_001171936,NM_022124,NM_052836" 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_022124" 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=605516" 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=05699&isoform_id=05699_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/CDH23" 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/6102888,12060937,14017841,16507964,18077851,18676668,21619654,21752756,37182356,40807027,50254104,50254106,50254112,50254114,54035160,80478612,119574811,119574812,119574813,119574814,119574815,119574816,119574817,146186735,189571674,229597137,229597167,284925128,284925130,284925132,284925134,284925136,284925138,284925140,408359994,444732969,929654677" 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/Q9H251" 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=64072" 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=ENSG00000107736;t=ENST00000224721" 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=CDH23" 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=CDH23" 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+64072" 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/CDH23" 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:64072" 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/64072" 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=chr10&hgg_gene=ENST00000224721.12&hgg_start=71396920&hgg_end=71815947&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:13733" 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:13733" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/gene/cdh23" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=605516[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=605516[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/CDH23/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/ENSG00000107736" 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=CDH23" 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=CDH23" 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=CDH23" 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="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
|
|
<div id="mimLocusSpecificDBsFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="http://hereditaryhearingloss.org/" title="Hereditary Hearing Loss Homepage" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Hereditary Hearing Loss Ho…</a></div><div style="margin-left: 0.5em;"><a href="http://www.LOVD.nl/CDH23" title="Retinal and hearing impairment genetic mutation database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Retinal and hearing impair…</a></div><div style="margin-left: 0.5em;"><a href="http://www.retina-international.org/files/sci-news/cdh23mut.htm" title="Mutations of the Cadherin-related Protein 23 Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Mutations of the Cadherin-…</a></div><div style="margin-left: 0.5em;"><a href="https://research.cchmc.org/LOVD2/home.php?select_db=CDH23" title="CCHMC - Human Genetics Mutation Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">CCHMC - Human Genetics Mut…</a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=CDH23&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/PA26296" 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:13733" 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/FBgn0036715.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:1890219" 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/CDH23#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:1890219" 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/64072/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/OMIA002584/" 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=64072" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-040513-7" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://reactome.org/content/query?q=CDH23&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
605516
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
CADHERIN 23; CDH23
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
OTOCADHERIN<br />
|
|
CADHERIN-RELATED FAMILY, MEMBER 23; CDHR23
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=CDH23" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CDH23</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/10/281?start=-3&limit=10&highlight=281">10q22.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr10:71396920-71815947&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'})">10:71,396,920-71,815,947</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=617540,601386,601067,601067" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="4">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/10/281?start=-3&limit=10&highlight=281">
|
|
10q22.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
{Pituitary adenoma 5, multiple types}
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/617540"> 617540 </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">
|
|
Deafness, autosomal recessive 12
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/601386"> 601386 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Usher syndrome, type 1D
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/601067"> 601067 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>, <abbr class="mim-tip-hint" title="Digenic recessive">DR</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">
|
|
Usher syndrome, type 1D/F digenic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/601067"> 601067 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>, <abbr class="mim-tip-hint" title="Digenic recessive">DR</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/605516" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/605516" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>The CDH23 gene encodes a member of the cadherin superfamily, which comprises calcium-dependent cell-cell adhesion glycoproteins (summary by <a href="#21" class="mim-tip-reference" title="Zhang, Q., Peng, C., Song, J., Zhang, Y., Chen, J., Song, Z., Shou, X., Ma, Z., Peng, H., Jian, X., He, W., Ye, Z., and 22 others. <strong>Germline mutations in CDH23, encoding cadherin-related 23, are associated with both familial and sporadic pituitary adenomas.</strong> Am. J. Hum. Genet. 100: 817-823, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28413019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28413019</a>] [<a href="https://doi.org/10.1016/j.ajhg.2017.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28413019">Zhang et al., 2017</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28413019" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Mouse chromosome 10 harbors several loci associated with hearing loss, including waltzer (v), modifier of deaf waddler (mdfw), and age-related hearing loss (Ahl). The orthologous human chromosomal region is 10q21-q22, which contains the human deafness loci DFNB12 (<a href="/entry/601386">601386</a>) and USH1D (<a href="/entry/601067">601067</a>). <a href="#8" class="mim-tip-reference" title="Di Palma, F., Holme, R. H., Bryda, E. C., Belyantseva, I. A., Pellegrino, R., Kachar, B., Steel, K. P., Noben-Trauth, K. <strong>Mutations in Cdh23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for Usher syndrome type 1D.</strong> Nature Genet. 27: 103-107, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138008</a>] [<a href="https://doi.org/10.1038/83660" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11138008">Di Palma et al. (2001)</a> identified the Cdh23 gene as that mutated in waltzer mice. The 10.5-kb Cdh23 cDNA encodes a large, single-pass transmembrane protein that <a href="#8" class="mim-tip-reference" title="Di Palma, F., Holme, R. H., Bryda, E. C., Belyantseva, I. A., Pellegrino, R., Kachar, B., Steel, K. P., Noben-Trauth, K. <strong>Mutations in Cdh23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for Usher syndrome type 1D.</strong> Nature Genet. 27: 103-107, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138008</a>] [<a href="https://doi.org/10.1038/83660" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11138008">Di Palma et al. (2001)</a> referred to as otocadherin. Cdh23 has an extracellular domain containing 27 repeats that show significant homology to the cadherin ectodomain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11138008" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Bolz, H., von Brederlow, B., Ramirez, A., Bryda, E. C., Kutsche, K., Nothwang, H. G., Seeliger, M., Cabrera, M. C.-S., Vila, M. C., Molina, O. P., Gal, A., Kubisch, C. <strong>Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D.</strong> Nature Genet. 27: 108-112, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138009</a>] [<a href="https://doi.org/10.1038/83667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11138009">Bolz et al. (2001)</a> found that the CDH23 gene encodes a predicted protein of 3,354 amino acids with a single transmembrane domain and 27 cadherin repeats. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11138009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>The CDH23 gene contains 69 exons (<a href="#20" class="mim-tip-reference" title="Wagatsuma, M., Kitoh, R., Suzuki, H., Fukuoka, H., Takumi, Y., Usami, S. <strong>Distribution and frequencies of CDH23 mutations in Japanese patients with non-syndromic hearing loss.</strong> Clin. Genet. 72: 339-344, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17850630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17850630</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00833.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17850630">Wagatsuma et al., 2007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17850630" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#16" class="mim-tip-reference" title="Siemens, J., Kazmierczak, P., Reynolds, A., Sticker, M., Littlewood-Evans, A., Muller, U. <strong>The Usher syndrome proteins cadherin 23 and harmonin form a complex by means of PDZ-domain interactions.</strong> Proc. Nat. Acad. Sci. 99: 14946-14951, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12407180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12407180</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12407180[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.232579599" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12407180">Siemens et al. (2002)</a> showed that CDH23 and harmonin (<a href="/entry/605242">605242</a>), another protein that is the site of mutations causing Usher syndrome, form a protein complex. Two PDZ domains in harmonin interact with 2 complementary binding surfaces in the CDH23 cytoplasmic domain. One of the binding surfaces is disrupted by sequences encoded by an alternatively spliced CDH23 exon that is expressed in the ear, but not in the retina. In the ear, CDH23 and harmonin are expressed in the stereocilia of hair cells, and in the retina within the photoreceptor cell layer. Because Cdh23-deficient mice have splayed stereocilia, <a href="#16" class="mim-tip-reference" title="Siemens, J., Kazmierczak, P., Reynolds, A., Sticker, M., Littlewood-Evans, A., Muller, U. <strong>The Usher syndrome proteins cadherin 23 and harmonin form a complex by means of PDZ-domain interactions.</strong> Proc. Nat. Acad. Sci. 99: 14946-14951, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12407180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12407180</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12407180[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.232579599" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12407180">Siemens et al. (2002)</a> suggested that CDH23 and harmonin are part of a transmembrane complex that connects stereocilia into a bundle, and that defects in the formation of this complex may disrupt stereocilia bundles and cause deafness in patients with Usher syndrome type I. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12407180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#4" class="mim-tip-reference" title="Boeda, B., El-Amraoui, A., Bahloul, A., Goodyear, R., Daviet, L., Blanchard, S., Perfettini, I., Fath, K. R., Shorte, S., Reiners, J., Houdusse, A., Legrain, P., Wolfrum, U., Richardson, G., Petit, C. <strong>Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle.</strong> EMBO J. 21: 6689-6699, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12485990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12485990</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12485990[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/emboj/cdf689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12485990">Boeda et al. (2002)</a> noted that 3 distinct genetic forms of Usher syndrome are caused by defects in the CDH23, harmonin, and MYO7A (<a href="/entry/276903">276903</a>) genes. They observed severely disorganized hair bundles in shaker-1 mice, which carry a mutation in the Myo7a gene. Immunohistochemical analysis of differentiating hair cells indicated that Cdh23 was distributed normally, but harmonin b was not. Using human and mouse cDNA constructs and cells, they confirmed interaction between harmonin and CDH23 in vitro and in vivo. They also provided evidence that harmonin b anchors CDH23 to the stereocilia microfilaments and interacts directly with MYO7A, which conveys harmonin b along the actin core of the developing stereocilia. <a href="#4" class="mim-tip-reference" title="Boeda, B., El-Amraoui, A., Bahloul, A., Goodyear, R., Daviet, L., Blanchard, S., Perfettini, I., Fath, K. R., Shorte, S., Reiners, J., Houdusse, A., Legrain, P., Wolfrum, U., Richardson, G., Petit, C. <strong>Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle.</strong> EMBO J. 21: 6689-6699, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12485990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12485990</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12485990[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/emboj/cdf689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12485990">Boeda et al. (2002)</a> proposed that the shaping of the hair bundle relies on a functional unit composed of MYO7A, harmonin b, and CDH23 and that the interaction of these proteins ensures the cohesion of the stereocilia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12485990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#9" class="mim-tip-reference" title="Hawkins, R. D., Lovett, M. <strong>The developmental genetics of auditory hair cells.</strong> Hum. Molec. Genet. 13: R289-R296, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15358736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15358736</a>] [<a href="https://doi.org/10.1093/hmg/ddh249" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15358736">Hawkins and Lovett (2004)</a> reviewed the developmental genetics of auditory hair cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15358736" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Kazmierczak, P., Sakaguchi, H., Tokita, J., Wilson-Kubalek, E. M., Milligan, R. A., Muller, U., Kachar, B. <strong>Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells.</strong> Nature 449: 87-91, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17805295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17805295</a>] [<a href="https://doi.org/10.1038/nature06091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17805295">Kazmierczak et al. (2007)</a> demonstrated that CDH23 and PCDH15 (<a href="/entry/605514">605514</a>), 2 cadherins that are linked to inherited forms of deafness in humans, interact to form tip links, extracellular filaments that connect the stereocilia and are thought to gate the mechanoelectrical transduction channel. Immunohistochemical studies using rodent hair cells showed that CDH23 and PCDH15 localized to the upper and lower part of tip links, respectively. The amino termini of the 2 cadherins colocalized on tip link filaments. Biochemical experiments showed that CDH23 homodimers interact in trans with PCDH15 homodimers to form a filament with structural similarity to tip links. Ions that affected tip link integrity and a mutation in PCDH15 that causes a recessive form of deafness (see DFNB23, <a href="/entry/609533">609533</a>) disrupted interactions between CDH23 and PCDH15. <a href="#10" class="mim-tip-reference" title="Kazmierczak, P., Sakaguchi, H., Tokita, J., Wilson-Kubalek, E. M., Milligan, R. A., Muller, U., Kachar, B. <strong>Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells.</strong> Nature 449: 87-91, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17805295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17805295</a>] [<a href="https://doi.org/10.1038/nature06091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17805295">Kazmierczak et al. (2007)</a> concluded that their studies defined the molecular composition of tip links and provided a conceptual base for exploring the mechanisms of sensory impairment associated with mutations in CDH23 and PCDH15. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17805295" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 molecular dynamic simulations, <a href="#17" class="mim-tip-reference" title="Sotomayor, M., Weihofen, W. A., Gaudet, R., Corey, D. P. <strong>Structural determinants of cadherin-23 function in hearing and deafness.</strong> Neuron 66: 85-100, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20399731/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20399731</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20399731[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2010.03.028" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20399731">Sotomayor et al. (2010)</a> found that the first 2 extracellular cadherin (EC) repeats of mouse Cdh23 were relatively stiff and required binding of 3 Ca(2+) ions at the linker region for mechanical integrity. <a href="#17" class="mim-tip-reference" title="Sotomayor, M., Weihofen, W. A., Gaudet, R., Corey, D. P. <strong>Structural determinants of cadherin-23 function in hearing and deafness.</strong> Neuron 66: 85-100, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20399731/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20399731</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20399731[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2010.03.028" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20399731">Sotomayor et al. (2010)</a> predicted that mutations in CDH23 that alter Ca(2+) binding could affect bending between the EC repeats, particularly at lower Ca(2+) concentrations, and alter the function of the stereocilia tip links. They proposed that lack of vestibular phenotypes in some Cdh23 mutant mice and DFNB12 patients may be due to the higher Ca(2+) concentration in vestibular endolymph compared with cochlear endolymph. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20399731" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Bahloul, A., Michel, V., Hardelin, J.-P., Nouaille, S., Hoos, S., Houdusse, A., England, P., Petit, C. <strong>Cadherin-23, myosin VIIa and harmonin, encoded by Usher syndrome type I genes, for a ternary complex and interact with membrane phospholipids.</strong> Hum. Molec. Genet. 19: 3557-3565, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20639393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20639393</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20639393[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/ddq271" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20639393">Bahloul et al. (2010)</a> found that isoforms of mouse Cdh23 that either included or excluded an exon 68-encoded sequence bound directly to the harmonin A isoform and to the tail of myosin-7a. The 3 proteins formed a complex that interacted with phosphatidylinositol 4,5-bisphosphate in synthetic liposomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20639393" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="biochemicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimBiochemicalFeaturesFold" id="mimBiochemicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimBiochemicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimBiochemicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
<a href="#18" class="mim-tip-reference" title="Sotomayor, M., Weihofen, W. A., Gaudet, R., Corey, D. P. <strong>Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction.</strong> Nature 492: 128-132, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23135401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23135401</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23135401[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/nature11590" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23135401">Sotomayor et al. (2012)</a> combined crystallography, molecular dynamics simulations, and binding experiments to characterize the protocadherin-15 (<a href="/entry/605514">605514</a>)-cadherin-23 bond. They found a unique cadherin interaction mechanism in which the 2 most N-terminal cadherin repeats (extracellular cadherin repeats 1 and 2) of each protein interact to form an overlapped, antiparallel heterodimer. Simulations predicted that this tip-link bond is mechanically strong enough to resist forces in hair cells. In addition, the complex was shown to become unstable in response to calcium removal owing to increased flexure of calcium-free cadherin repeats. Finally, <a href="#18" class="mim-tip-reference" title="Sotomayor, M., Weihofen, W. A., Gaudet, R., Corey, D. P. <strong>Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction.</strong> Nature 492: 128-132, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23135401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23135401</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23135401[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/nature11590" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23135401">Sotomayor et al. (2012)</a> used structures and biochemical measurements to study the molecular mechanisms by which deafness mutations disrupt tip-link function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23135401" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Usher Syndrome Type ID</em></strong></p><p>
|
|
<a href="#5" class="mim-tip-reference" title="Bolz, H., von Brederlow, B., Ramirez, A., Bryda, E. C., Kutsche, K., Nothwang, H. G., Seeliger, M., Cabrera, M. C.-S., Vila, M. C., Molina, O. P., Gal, A., Kubisch, C. <strong>Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D.</strong> Nature Genet. 27: 108-112, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138009</a>] [<a href="https://doi.org/10.1038/83667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11138009">Bolz et al. (2001)</a> identified a Cuban pedigree in which type I Usher syndrome was linked to the USH1D locus on chromosome 10 (see <a href="/entry/601067">601067</a>). Affected individuals presented with congenital deafness and a highly variable degree of retinal degeneration as an autosomal recessive trait. Using a positional candidate approach, <a href="#5" class="mim-tip-reference" title="Bolz, H., von Brederlow, B., Ramirez, A., Bryda, E. C., Kutsche, K., Nothwang, H. G., Seeliger, M., Cabrera, M. C.-S., Vila, M. C., Molina, O. P., Gal, A., Kubisch, C. <strong>Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D.</strong> Nature Genet. 27: 108-112, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138009</a>] [<a href="https://doi.org/10.1038/83667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11138009">Bolz et al. (2001)</a> identified CDH23 as the gene responsible for USH1D in these individuals. In the Cuban family, the authors detected 2 different CDH23 mutations. A severe course of the retinal disease was observed in individuals homozygous for a presumed truncating splice site mutation (<a href="#0001">605516.0001</a>), whereas mild retinitis pigmentosa was present in individuals carrying a homozygous missense mutation (<a href="#0002">605516.0002</a>). Variable expression of the retinal phenotype was seen in patients with a combination of the 2 mutations. <a href="#5" class="mim-tip-reference" title="Bolz, H., von Brederlow, B., Ramirez, A., Bryda, E. C., Kutsche, K., Nothwang, H. G., Seeliger, M., Cabrera, M. C.-S., Vila, M. C., Molina, O. P., Gal, A., Kubisch, C. <strong>Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D.</strong> Nature Genet. 27: 108-112, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138009</a>] [<a href="https://doi.org/10.1038/83667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11138009">Bolz et al. (2001)</a> also identified 2 mutations in the CDH23 gene in a German patient with Usher syndrome (<a href="#0003">605516.0003</a>-<a href="#0004">605516.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11138009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Simultaneously and independently, <a href="#6" class="mim-tip-reference" title="Bork, J. M., Peters, L. M., Riazuddin, S., Bernstein, S. L., Ahmed, Z. M., Ness, S. L., Polomeno, R., Ramesh, A., Schloss, M., Srisailpathy, C. R. S., Wayne, S., Bellman, S., and 16 others. <strong>Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23.</strong> Am. J. Hum. Genet. 68: 26-37, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11090341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11090341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11090341[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/10.1086/316954" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11090341">Bork et al. (2001)</a> identified 2 nonsense and 2 frameshift mutations in the CDH23 gene (see, e.g., <a href="#0007">605516.0007</a>) in 4 families with USH1D. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11090341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 33 patients with type I Usher syndrome in whom USH1B (<a href="/entry/276903">276903</a>) and USH1C (<a href="/entry/605242">605242</a>) had been excluded, <a href="#19" class="mim-tip-reference" title="von Brederlow, B., Bolz, H., Janecke, A., La O Cabrera, A., Rudolph, G., Lorenz, B., Schwinger, E., Gal, A. <strong>Identification and in vitro expression of novel CDH23 mutations of patients with Usher syndrome type 1D.</strong> Hum. Mutat. 19: 268-273, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11857743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11857743</a>] [<a href="https://doi.org/10.1002/humu.10049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11857743">von Brederlow et al. (2002)</a> performed mutation screening by single-strand conformation polymorphism (SSCP) analysis and direct sequencing. On 8 disease alleles of 4 patients, 4 different mutations in the CDH23 gene were identified, 3 of them being novel. Among a total of 52 type I Usher cases studied by this group, CDH23 mutations accounted for about 10% of all disease alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11857743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Only missense mutations of CDH23 have been observed in families with nonsyndromic deafness, whereas nonsense, frameshift, splice-site, and missense mutations have been identified in families with Usher syndrome. <a href="#1" class="mim-tip-reference" title="Astuto, L. M., Bork, J. M., Weston, M. D., Askew, J. W., Fields, R. R., Orten, D. J., Ohliger, S. J., Riazuddin, S., Morell, R. J., Khan, S., Riazuddin, S., Kremer, H., and 15 others. <strong>CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness.</strong> Am. J. Hum. Genet. 71: 262-275, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12075507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12075507</a>] [<a href="https://doi.org/10.1086/341558" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12075507">Astuto et al. (2002)</a> screened a panel of 69 probands with Usher syndrome and 38 probands with recessive nonsyndromic deafness for the presence of mutations in the entire coding region of CDH23, by heteroduplex, SSCP, and direct sequence analyses. Thirty-six different CDH23 mutations were detected in 45 families; 33 of these mutations were novel, including 18 missense, 3 nonsense, 5 splicing defects, 5 microdeletions, and 2 insertions. Seven mutations were common to more than 1 family. Ophthalmologic examination of patients with nonsyndromic deafness revealed asymptomatic manifestations similar to retinitis pigmentosa (RP; <a href="/entry/268000">268000</a>), which indicated that missense mutations may have a subtle effect in the retina. Furthermore, patients with mutations in CDH23 displayed a wide range of hearing loss and RP phenotypes, differing in severity, age at onset, type, and the presence or absence of vestibular areflexia. <a href="#1" class="mim-tip-reference" title="Astuto, L. M., Bork, J. M., Weston, M. D., Askew, J. W., Fields, R. R., Orten, D. J., Ohliger, S. J., Riazuddin, S., Morell, R. J., Khan, S., Riazuddin, S., Kremer, H., and 15 others. <strong>CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness.</strong> Am. J. Hum. Genet. 71: 262-275, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12075507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12075507</a>] [<a href="https://doi.org/10.1086/341558" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12075507">Astuto et al. (2002)</a> also presented a comprehensive catalog of CDH23 mutations identified both in their study and in patients reported elsewhere with either recessive nonsyndromic deafness or Usher syndrome type I. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12075507" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Autosomal Recessive Deafness 12</em></strong></p><p>
|
|
In 5 families segregating autosomal recessive nonsyndromic hearing loss (DFNB12; <a href="/entry/601386">601386</a>), <a href="#6" class="mim-tip-reference" title="Bork, J. M., Peters, L. M., Riazuddin, S., Bernstein, S. L., Ahmed, Z. M., Ness, S. L., Polomeno, R., Ramesh, A., Schloss, M., Srisailpathy, C. R. S., Wayne, S., Bellman, S., and 16 others. <strong>Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23.</strong> Am. J. Hum. Genet. 68: 26-37, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11090341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11090341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11090341[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/10.1086/316954" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11090341">Bork et al. (2001)</a> identified 6 missense mutations in the CDH23 gene (see, e.g., <a href="#0005">605516.0005</a>-<a href="#0006">605516.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11090341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 5 sibs, born of consanguineous parents, with autosomal recessive deafness, <a href="#14" class="mim-tip-reference" title="Schultz, J. M., Yang, Y., Caride, A. J., Filoteo, A. G., Penheiter, A. R., Lagziel, A., Morell, R. J., Mohiddin, S. A., Fananapazir, L., Madeo, A. C., Penniston, J. T., Griffith, A. J. <strong>Modification of human hearing loss by plasma-membrane calcium pump PMCA2.</strong> New Eng. J. Med. 352: 1557-1564, 2005. Note: Erratum: New Eng. J. Med. 352: 2362 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15829536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15829536</a>] [<a href="https://doi.org/10.1056/NEJMoa043899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15829536">Schultz et al. (2005)</a> identified a homozygous phe1888-to-ser substitution in the CDH23 gene (F1888S; <a href="#0010">605516.0010</a>). Two of the sibs had high frequency hearing loss and 3 had severe to profound hearing loss affecting all frequencies. The 3 severely affected sibs were additionally heterozygous for a val586-to-met substitution in the ATP2B2 gene (V586M; <a href="/entry/108733#0001">108733.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15829536" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Wagatsuma, M., Kitoh, R., Suzuki, H., Fukuoka, H., Takumi, Y., Usami, S. <strong>Distribution and frequencies of CDH23 mutations in Japanese patients with non-syndromic hearing loss.</strong> Clin. Genet. 72: 339-344, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17850630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17850630</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00833.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17850630">Wagatsuma et al. (2007)</a> identified homozygosity or compound heterozygosity for 4 different missense mutations in the CDH23 gene (see, e.g., <a href="#0014">605516.0014</a> and <a href="#0015">605516.0015</a>) in 6 Japanese patients from 5 families with autosomal recessive hearing loss. All four mutations were in the extracellular domain of the protein. The findings indicated that mutations in the CDH23 gene may account for about 5% of nonsyndromic hearing loss in the Japanese population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17850630" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Usher Syndrome Type ID/F</em></strong></p><p>
|
|
<a href="#22" class="mim-tip-reference" title="Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., Liu, X. Z. <strong>Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.</strong> Hum. Molec. Genet. 14: 103-111, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15537665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15537665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15537665[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/ddi010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15537665">Zheng et al. (2005)</a> reported 3 families with Usher syndrome type I in which affected members carried mutations in both CDH23 and PCDH15 (<a href="/entry/605514">605514</a>), thus supporting a digenic model for some individuals with this phenotype. Based on an animal model, the authors concluded that CDH23 and PCDH15 play an essential long-term role in maintaining the normal organization of the stereocilia bundle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15537665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Pituitary Adenoma 5, Susceptibility to</em></strong></p><p>
|
|
In affected members of 4 unrelated families with both functional GH-secreting and nonfunctional pituitary adenomas (PITA5; <a href="/entry/617540">617540</a>), <a href="#21" class="mim-tip-reference" title="Zhang, Q., Peng, C., Song, J., Zhang, Y., Chen, J., Song, Z., Shou, X., Ma, Z., Peng, H., Jian, X., He, W., Ye, Z., and 22 others. <strong>Germline mutations in CDH23, encoding cadherin-related 23, are associated with both familial and sporadic pituitary adenomas.</strong> Am. J. Hum. Genet. 100: 817-823, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28413019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28413019</a>] [<a href="https://doi.org/10.1016/j.ajhg.2017.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28413019">Zhang et al. (2017)</a> identified germline heterozygous missense mutations in the CDH23 gene (<a href="#0016">605516.0016</a>-<a href="#0019">605516.0019</a>). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. There was evidence of age-dependent or incomplete penetrance. Whole-exome sequencing of 125 individuals with sporadic pituitary adenomas identified CDH23 mutations in 15 individuals (12.0%); 13 had heterozygous mutations and 2 had homozygous mutations. The tumor types in these patients varied. All mutations identified occurred at highly conserved residues in the EC domains of CDH23 and were predicted to adversely affect calcium binding or protein folding. Functional studies of the variants were not performed. Compared to pituitary adenomas with wildtype CDH23, those associated with CDH23 mutations were smaller in diameter and less invasive. Heterozygous, putatively functional variants in the CDH23 gene were found in 2 (0.8%) of 260 control individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28413019" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="genotypePhenotypeCorrelations" class="mim-anchor"></a>
|
|
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGenotypePhenotypeCorrelationsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>DFNB12 is associated with CDH23 missense mutations that are presumed to be hypomorphic alleles with sufficient residual activity for retinal and vestibular function, but not for auditory cochlear function. In contrast, homozygous nonsense, frameshift, splice site, and some missense mutations of CDH23, or a combination of these USH1D alleles in a compound heterozygote, cause USH1D. <a href="#13" class="mim-tip-reference" title="Schultz, J. M., Bhatti, R., Madeo, A. C., Turriff, A., Muskett, J. A., Zalewski, C. K., King, K. A., Ahmed, Z. M., Riazuddin, S., Ahmad, N., Hussain, Z., Qasim, M., and 12 others. <strong>Allelic hierarchy of CDH23 mutations causing non-syndromic deafness DFNB12 or Usher syndrome USH1D in compound heterozygotes.</strong> J. Med. Genet. 48: 767-775, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21940737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21940737</a>] [<a href="https://doi.org/10.1136/jmedgenet-2011-100262" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21940737">Schultz et al. (2011)</a> identified 12 different homozygous CDH23 mutations, including 8 novel mutations, in 13 families with DFNB12. All were missense, except 1 in-frame deletion. Ten different homozygous mutations were found in 14 families and 1 singleton with USH1D. These latter mutations were mostly nonsense, frameshift, or splice site mutations, but there was 1 in-frame deletion and 2 missense mutations. Affected individuals in 3 additional families were found to carry compound heterozygous mutations in the CDH23 gene, with the different alleles being associated with either DFNB12 or USH1D. Based on the phenotypes within families, the results indicated that USH1D occurs only when there are 2 USH1D alleles in trans. In contrast, when there is a DFNB12 allele in trans with a USH1D allele, the phenotype is DFNB12. The findings indicated that a DFNB12 allele is phenotypically dominant to a USH1D allele, and can preserve normal retinal and vestibular function even in the presence of a USH1D allele. <a href="#13" class="mim-tip-reference" title="Schultz, J. M., Bhatti, R., Madeo, A. C., Turriff, A., Muskett, J. A., Zalewski, C. K., King, K. A., Ahmed, Z. M., Riazuddin, S., Ahmad, N., Hussain, Z., Qasim, M., and 12 others. <strong>Allelic hierarchy of CDH23 mutations causing non-syndromic deafness DFNB12 or Usher syndrome USH1D in compound heterozygotes.</strong> J. Med. Genet. 48: 767-775, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21940737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21940737</a>] [<a href="https://doi.org/10.1136/jmedgenet-2011-100262" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21940737">Schultz et al. (2011)</a> noted the implications for genetic counseling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21940737" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#8" class="mim-tip-reference" title="Di Palma, F., Holme, R. H., Bryda, E. C., Belyantseva, I. A., Pellegrino, R., Kachar, B., Steel, K. P., Noben-Trauth, K. <strong>Mutations in Cdh23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for Usher syndrome type 1D.</strong> Nature Genet. 27: 103-107, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138008</a>] [<a href="https://doi.org/10.1038/83660" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11138008">Di Palma et al. (2001)</a> identified loss-of-function mutations in the Cdh23 gene in each of 3 different waltzer alleles. They demonstrated that Cdh23 is expressed in the neurosensory epithelium. During early hair cell differentiation, stereocilia organization was disrupted in homozygotes for one of the mutant alleles. The data indicated that Cdh23 is a critical component of hair bundle formation. The demonstration of mutations in the human CDH23 gene in USH1D established waltzer as the mouse model for USH1D. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11138008" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Age-related hearing loss (AHL) in common inbred mouse strains is a genetically complex quantitative trait. <a href="#12" class="mim-tip-reference" title="Noben-Trauth, K., Zheng, Q. Y., Johnson, K. R. <strong>Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss.</strong> Nature Genet. 35: 21-23, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12910270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12910270</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12910270[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/ng1226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12910270">Noben-Trauth et al. (2003)</a> found a synonymous single-nucleotide polymorphism (SNP) in exon 7 of the Cdh23 gene that showed significant association with AHL and the deafness modifier mdfw (modifier of deafwaddler). The hypomorphic Cdh23(753A) allele caused in-frame skipping of exon 7. Altered adhesion or reduced stability of CDH23 may confer susceptibility to AHL. Homozygosity at Cdh23(753A) or in combination with heterogeneous secondary factors was found to be a primary determinant of AHL in mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12910270" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#22" class="mim-tip-reference" title="Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., Liu, X. Z. <strong>Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.</strong> Hum. Molec. Genet. 14: 103-111, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15537665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15537665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15537665[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/ddi010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15537665">Zheng et al. (2005)</a> generated mice that were heterozygous for both Cdh23(v-2J) and Pcdh15(av-3J) (<a href="/entry/605514">605514</a>) mutations on a uniform C57BL/6J background. Significant levels of hearing loss were detected in these mice when compared to age-matched single heterozygous animals or normal controls, which supported a digenic model of hearing loss. Cytoarchitectural defects in the cochlea of digenic heterozygotes, including degeneration of the stereocilia and a base-apex loss of hair cells and spiral ganglion cells, were consistent with the observed age-related hearing loss of these mice beginning with the high frequencies. The authors noted that while hearing loss was progressive in these animals, humans with heterozygosity for both CDH23 and PCDH15 mutations are congenitally deaf. <a href="#22" class="mim-tip-reference" title="Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., Liu, X. Z. <strong>Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.</strong> Hum. Molec. Genet. 14: 103-111, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15537665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15537665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15537665[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/ddi010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15537665">Zheng et al. (2005)</a> concluded that CDH23 and PCDH15 play an essential long-term role in maintaining the normal organization of the stereocilia bundle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15537665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an N-ethyl-N-nitrosourea (ENU) mutagenesis screen, <a href="#15" class="mim-tip-reference" title="Schwander, M., Xiong, W., Tokita, J., Lelli, A., Elledge, H. M., Kazmierczak, P., Sczaniecka, A., Kolatkar, A., Wiltshire, T., Kuhn, P., Holt, J. R., Kachar, B., Tarantino, L., Muller, U. <strong>A mouse model for nonsyndromic deafness (DFNB12) links hearing loss to defects in tip links of mechanosensory hair cells.</strong> Proc. Nat. Acad. Sci. 106: 5252-5257, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19270079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19270079</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19270079[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.0900691106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19270079">Schwander et al. (2009)</a> identified 'salsa' mice, which suffer from progressive hearing loss and carry a Cdh23 mutation (E737V) that is predicted to affect Ca(2+) binding by the extracellular domain. Otoacoustic emissions were not detected, suggesting a defect in outer hair cell function. Similar mutations in the human CDH23 gene cause DFNB12. Although hair bundle development appeared unaffected in salsa mice, tip links were progressively lost, resulting in hair cell death. Tip links in vestibular hair cells were unaffected. Biochemical studies showed that mutant Cdh23 had impaired interaction with Pcdh15. The findings suggested that missense mutations in DFNB12 patients lead to deafness by affecting tip links. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19270079" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Bahloul, A., Michel, V., Hardelin, J.-P., Nouaille, S., Hoos, S., Houdusse, A., England, P., Petit, C. <strong>Cadherin-23, myosin VIIa and harmonin, encoded by Usher syndrome type I genes, for a ternary complex and interact with membrane phospholipids.</strong> Hum. Molec. Genet. 19: 3557-3565, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20639393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20639393</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20639393[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/ddq271" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20639393">Bahloul et al. (2010)</a> found that knockout of Cdh23 in mice resulted in loss of harmonin from the apex of hair bundles in the organ of Corti and caused redistribution of a weakened myosin-7a signal along stereocilia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20639393" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>19 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/605516" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=605516[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 USHER SYNDROME, TYPE ID</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, GLN1496HIS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908347 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908347;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=rs121908347" 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=rs121908347" 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=RCV000005197 OR RCV001566890 OR RCV001835621 OR RCV003472971" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005197, RCV001566890, RCV001835621, RCV003472971" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005197...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Cuban family with Usher syndrome type ID (USH1D; <a href="/entry/601067">601067</a>), <a href="#5" class="mim-tip-reference" title="Bolz, H., von Brederlow, B., Ramirez, A., Bryda, E. C., Kutsche, K., Nothwang, H. G., Seeliger, M., Cabrera, M. C.-S., Vila, M. C., Molina, O. P., Gal, A., Kubisch, C. <strong>Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D.</strong> Nature Genet. 27: 108-112, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138009</a>] [<a href="https://doi.org/10.1038/83667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11138009">Bolz et al. (2001)</a> identified a G-to-C transversion at nucleotide 4488 of the CDH23 gene, leading to a gln1496-to-his (Q1496H) mutation. The mutation resulted in aberrant splicing in an in vitro assay. Homozygotes for this mutation had a severe course of retinal disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11138009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 USHER SYNDROME, TYPE ID</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, ARG1746GLN
|
|
</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> rs111033270 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033270;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/rs111033270?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=rs111033270" 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=rs111033270" 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=RCV000005198 OR RCV000254732 OR RCV000763215 OR RCV000844622 OR RCV001073594 OR RCV001274889 OR RCV001328020 OR RCV002222340 OR RCV002272010 OR RCV002512799 OR RCV003472972 OR RCV004528082" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005198, RCV000254732, RCV000763215, RCV000844622, RCV001073594, RCV001274889, RCV001328020, RCV002222340, RCV002272010, RCV002512799, RCV003472972, RCV004528082" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005198...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Cuban family with Usher syndrome type ID (USH1D; <a href="/entry/601067">601067</a>), <a href="#5" class="mim-tip-reference" title="Bolz, H., von Brederlow, B., Ramirez, A., Bryda, E. C., Kutsche, K., Nothwang, H. G., Seeliger, M., Cabrera, M. C.-S., Vila, M. C., Molina, O. P., Gal, A., Kubisch, C. <strong>Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D.</strong> Nature Genet. 27: 108-112, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138009</a>] [<a href="https://doi.org/10.1038/83667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11138009">Bolz et al. (2001)</a> identified a G-to-A transition at nucleotide 5237 of the CDH23 gene, resulting in an arg1746-to-gln (R1746Q) mutation. Homozygotes for this mutation had mild retinitis pigmentosa. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11138009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 USHER SYNDROME, TYPE ID</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, 3-BP DEL, 3841ATG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs796051860 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs796051860;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=rs796051860" 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=rs796051860" 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=RCV000005199 OR RCV005089176" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005199, RCV005089176" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005199...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a German patient with Usher syndrome type ID (USH1D; <a href="/entry/601067">601067</a>), <a href="#5" class="mim-tip-reference" title="Bolz, H., von Brederlow, B., Ramirez, A., Bryda, E. C., Kutsche, K., Nothwang, H. G., Seeliger, M., Cabrera, M. C.-S., Vila, M. C., Molina, O. P., Gal, A., Kubisch, C. <strong>Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D.</strong> Nature Genet. 27: 108-112, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138009</a>] [<a href="https://doi.org/10.1038/83667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11138009">Bolz et al. (2001)</a> identified compound heterozygosity for 2 mutations in the CDH23 gene: a 3-bp deletion at nucleotide 3841, resulting in the deletion of met1281, and a G-to-A transition at the +5 position of intron 51 (<a href="#0004">605516.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11138009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 USHER SYNDROME, TYPE ID</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, IVS51, G-A, +5
|
|
</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> rs727502931 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs727502931;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/rs727502931?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=rs727502931" 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=rs727502931" 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=RCV000005200 OR RCV000844693 OR RCV001851662 OR RCV003472973" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005200, RCV000844693, RCV001851662, RCV003472973" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005200...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the G-to-A transition at the +5 position of intron 51 in the CDH23 gene that was found in compound heterozygous state in a patient with Usher syndrome type ID (USH1D; <a href="/entry/601067">601067</a>) by <a href="#5" class="mim-tip-reference" title="Bolz, H., von Brederlow, B., Ramirez, A., Bryda, E. C., Kutsche, K., Nothwang, H. G., Seeliger, M., Cabrera, M. C.-S., Vila, M. C., Molina, O. P., Gal, A., Kubisch, C. <strong>Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D.</strong> Nature Genet. 27: 108-112, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138009</a>] [<a href="https://doi.org/10.1038/83667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11138009">Bolz et al. (2001)</a>, see <a href="#0003">605516.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11138009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 DEAFNESS, AUTOSOMAL RECESSIVE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, ASP1243ASN
|
|
</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> rs121908348 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908348;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/rs121908348?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=rs121908348" 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=rs121908348" 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=RCV000005201 OR RCV001291217 OR RCV003472974" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005201, RCV001291217, RCV003472974" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005201...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with autosomal recessive deafness-12 (DFNB12; <a href="/entry/601386">601386</a>), <a href="#6" class="mim-tip-reference" title="Bork, J. M., Peters, L. M., Riazuddin, S., Bernstein, S. L., Ahmed, Z. M., Ness, S. L., Polomeno, R., Ramesh, A., Schloss, M., Srisailpathy, C. R. S., Wayne, S., Bellman, S., and 16 others. <strong>Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23.</strong> Am. J. Hum. Genet. 68: 26-37, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11090341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11090341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11090341[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/10.1086/316954" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11090341">Bork et al. (2001)</a> identified an asp1243-to-asn (D1243N) mutation in the CDH23 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11090341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 DEAFNESS, AUTOSOMAL RECESSIVE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, ASP1400ASN
|
|
</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> rs121908349 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908349;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/rs121908349?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=rs121908349" 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=rs121908349" 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=RCV000005202 OR RCV000818407 OR RCV001291219 OR RCV001831514 OR RCV003387716 OR RCV003472975 OR RCV005041985" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005202, RCV000818407, RCV001291219, RCV001831514, RCV003387716, RCV003472975, RCV005041985" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005202...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with autosomal recessive deafness-12 (DFNB12; <a href="/entry/601386">601386</a>), <a href="#6" class="mim-tip-reference" title="Bork, J. M., Peters, L. M., Riazuddin, S., Bernstein, S. L., Ahmed, Z. M., Ness, S. L., Polomeno, R., Ramesh, A., Schloss, M., Srisailpathy, C. R. S., Wayne, S., Bellman, S., and 16 others. <strong>Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23.</strong> Am. J. Hum. Genet. 68: 26-37, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11090341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11090341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11090341[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/10.1086/316954" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11090341">Bork et al. (2001)</a> found that affected members had an asp1400-to-asn (D1400N) mutation in the CDH23 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11090341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 USHER SYNDROME, TYPE ID</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, GLN492TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908350 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908350;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=rs121908350" 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=rs121908350" 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=RCV000005203 OR RCV001291211 OR RCV001386699" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005203, RCV001291211, RCV001386699" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005203...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with Usher syndrome type ID (USHID; <a href="/entry/601067">601067</a>), <a href="#6" class="mim-tip-reference" title="Bork, J. M., Peters, L. M., Riazuddin, S., Bernstein, S. L., Ahmed, Z. M., Ness, S. L., Polomeno, R., Ramesh, A., Schloss, M., Srisailpathy, C. R. S., Wayne, S., Bellman, S., and 16 others. <strong>Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23.</strong> Am. J. Hum. Genet. 68: 26-37, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11090341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11090341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11090341[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/10.1086/316954" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11090341">Bork et al. (2001)</a> found that affected members had a gln492-to-ter (Q492X) mutation in the CDH23 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11090341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 DEAFNESS, AUTOSOMAL RECESSIVE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, ASP2148ASN
|
|
</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> rs111033271 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033271;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/rs111033271?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=rs111033271" 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=rs111033271" 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=RCV000005204 OR RCV000599622 OR RCV000710063 OR RCV000809058 OR RCV001826421 OR RCV003472976 OR RCV003987312 OR RCV004757097 OR RCV004783719 OR RCV004814828 OR RCV005041986" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005204, RCV000599622, RCV000710063, RCV000809058, RCV001826421, RCV003472976, RCV003987312, RCV004757097, RCV004783719, RCV004814828, RCV005041986" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005204...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 presumably unrelated families with autosomal recessive nonsyndromic deafness mapping to chromosome 10q (DFNB12; <a href="/entry/601386">601386</a>), <a href="#1" class="mim-tip-reference" title="Astuto, L. M., Bork, J. M., Weston, M. D., Askew, J. W., Fields, R. R., Orten, D. J., Ohliger, S. J., Riazuddin, S., Morell, R. J., Khan, S., Riazuddin, S., Kremer, H., and 15 others. <strong>CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness.</strong> Am. J. Hum. Genet. 71: 262-275, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12075507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12075507</a>] [<a href="https://doi.org/10.1086/341558" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12075507">Astuto et al. (2002)</a> found an asp2148-to-asn (D2148N) mutation in the CDH23 gene, located in exon 47 in extracellular domain 20. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12075507" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="de Brouwer, A. P. M., Pennings, R. J. E., Roeters, M., Van Hauwe, P., Astuto, L. M., Hoefsloot, L. H., Huygen, P. L. M., van den Helm, B., Deutman, A. F., Bork, J. M., Kimberling, W. J., Cremers, F. P. M., Cremers, C. W. R. J., Kremer, H. <strong>Mutations in the calcium-binding motifs of CDH23 and the 35delG mutation in GJB2 cause hearing loss in one family.</strong> Hum. Genet. 112: 156-163, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12522556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12522556</a>] [<a href="https://doi.org/10.1007/s00439-002-0833-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12522556">De Brouwer et al. (2003)</a> performed a genetic analysis of a large consanguineous family with DFNB12 that was previously described by <a href="#11" class="mim-tip-reference" title="Marres, H. A. M., Cremers, C. W. R. J. <strong>Autosomal recessive nonsyndromal profound childhood deafness in a large pedigree: audiometric features of the affected persons and the obligate carriers.</strong> Arch. Otolaryng. Head Neck Surg. 115: 591-595, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2706105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2706105</a>] [<a href="https://doi.org/10.1001/archotol.1989.01860290049013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2706105">Marres and Cremers (1989)</a>. Patients in 1 branch of the family were homozygous for the 35delG mutation in the GJB2 gene (<a href="/entry/121011#0005">121011.0005</a>) causing DFNB1 (<a href="/entry/220290">220290</a>). Patients in 2 other branches carried 2 novel mutations in the CDH23 gene causing DFNB12: a homozygous 6442G-A transition in exon 47 causing the D2148N mutation in 1 branch, and compound heterozygosity for this mutation and a 4021G-A transition causing an asp1341-to-asn (D1341N) mutation (<a href="#0009">605516.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12522556+2706105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 DEAFNESS, AUTOSOMAL RECESSIVE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, ASP1341ASN
|
|
</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> rs121908351 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908351;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/rs121908351?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=rs121908351" 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=rs121908351" 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=RCV000005205 OR RCV000436619 OR RCV001272891 OR RCV003472977 OR RCV003492284" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005205, RCV000436619, RCV001272891, RCV003472977, RCV003492284" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005205...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the asp1341-to-asn (D1341N) mutation in the CDH23 gene that was found in compound heterozygous state in patients with autosomal recessive deafness-12 (DFNB12; <a href="/entry/601386">601386</a>) by <a href="#7" class="mim-tip-reference" title="de Brouwer, A. P. M., Pennings, R. J. E., Roeters, M., Van Hauwe, P., Astuto, L. M., Hoefsloot, L. H., Huygen, P. L. M., van den Helm, B., Deutman, A. F., Bork, J. M., Kimberling, W. J., Cremers, F. P. M., Cremers, C. W. R. J., Kremer, H. <strong>Mutations in the calcium-binding motifs of CDH23 and the 35delG mutation in GJB2 cause hearing loss in one family.</strong> Hum. Genet. 112: 156-163, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12522556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12522556</a>] [<a href="https://doi.org/10.1007/s00439-002-0833-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12522556">de Brouwer et al. (2003)</a>, see <a href="#0008">605516.0008</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12522556" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 DEAFNESS, AUTOSOMAL RECESSIVE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, PHE1888SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121908352 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908352;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=rs121908352" 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=rs121908352" 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=RCV000005206 OR RCV001851663" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005206, RCV001851663" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005206...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 sibs, born of consanguineous parents, with autosomal recessive deafness-12 (DFNB12; <a href="/entry/601386">601386</a>), <a href="#14" class="mim-tip-reference" title="Schultz, J. M., Yang, Y., Caride, A. J., Filoteo, A. G., Penheiter, A. R., Lagziel, A., Morell, R. J., Mohiddin, S. A., Fananapazir, L., Madeo, A. C., Penniston, J. T., Griffith, A. J. <strong>Modification of human hearing loss by plasma-membrane calcium pump PMCA2.</strong> New Eng. J. Med. 352: 1557-1564, 2005. Note: Erratum: New Eng. J. Med. 352: 2362 only, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15829536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15829536</a>] [<a href="https://doi.org/10.1056/NEJMoa043899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15829536">Schultz et al. (2005)</a> identified a homozygous 5663T-C transition in exon 42 of the CDH23 gene, resulting in a phe1888-to-ser (F1888S) substitution in the extracellular domain of the protein. Two of the sibs had high frequency hearing loss and 3 had severe to profound hearing loss affecting all frequencies. The 3 severely affected sibs were heterozygous for a val586-to-met substitution in the ATP2B2 gene (V586M; <a href="/entry/108733#0001">108733.0001</a>). Variants in ATP2B2, the plasma membrane calcium pump, modulate the severity of hearing loss in mice with mutations in the CDH23 gene (<a href="#12" class="mim-tip-reference" title="Noben-Trauth, K., Zheng, Q. Y., Johnson, K. R. <strong>Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss.</strong> Nature Genet. 35: 21-23, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12910270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12910270</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12910270[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/ng1226" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12910270">Noben-Trauth et al., 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15829536+12910270" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 USHER SYNDROME, TYPE ID</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
USHER SYNDROME, TYPE ID/F, DIGENIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, 1-BP DEL, 193C
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs796051861 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs796051861;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=rs796051861" 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=rs796051861" 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=RCV000005207 OR RCV000005208 OR RCV000215123 OR RCV000254862 OR RCV005041987" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005207, RCV000005208, RCV000215123, RCV000254862, RCV005041987" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005207...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a proband with a diagnosis of Usher syndrome type I (see <a href="/entry/601067">601067</a>), <a href="#22" class="mim-tip-reference" title="Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., Liu, X. Z. <strong>Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.</strong> Hum. Molec. Genet. 14: 103-111, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15537665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15537665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15537665[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/ddi010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15537665">Zheng et al. (2005)</a> found compound heterozygosity for a 1-bp deletion of the CDH23 gene, 193delC, and a 3-bp deletion in the PCDH15 gene (<a href="/entry/605514#0005">605514.0005</a>). The 193delC mutation was previously found in a patient with Usher syndrome type ID (USH1D) by <a href="#1" class="mim-tip-reference" title="Astuto, L. M., Bork, J. M., Weston, M. D., Askew, J. W., Fields, R. R., Orten, D. J., Ohliger, S. J., Riazuddin, S., Morell, R. J., Khan, S., Riazuddin, S., Kremer, H., and 15 others. <strong>CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness.</strong> Am. J. Hum. Genet. 71: 262-275, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12075507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12075507</a>] [<a href="https://doi.org/10.1086/341558" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12075507">Astuto et al. (2002)</a>. The CDH23 193delC mutation consists of deletion of a single C in a CCCCC string in exon 3, which causes a frameshift at codon 65 in the first extracellular repeat domain and a stop codon 48 amino acids downstream. The resulting truncated protein lacked approximately 96% of the predicted coding sequence. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12075507+15537665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 USHER SYNDROME, TYPE ID/F, DIGENIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, ARG3189TRP
|
|
</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> rs121908353 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908353;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/rs121908353?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=rs121908353" 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=rs121908353" 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=RCV000005209 OR RCV000039312 OR RCV000222140 OR RCV000787978 OR RCV001358062 OR RCV002482830" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005209, RCV000039312, RCV000222140, RCV000787978, RCV001358062, RCV002482830" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005209...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a proband with a diagnosis of Usher syndrome type I (see <a href="/entry/601067">601067</a>), <a href="#22" class="mim-tip-reference" title="Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., Liu, X. Z. <strong>Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.</strong> Hum. Molec. Genet. 14: 103-111, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15537665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15537665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15537665[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/ddi010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15537665">Zheng et al. (2005)</a> found compound heterozygosity for a C-to-T transition at nucleotide 9565 of the CDH23 gene and a 1-bp deletion in the PCDH15 gene (16delT; <a href="/entry/605514#0008">605514.0008</a>). The 9565C-T mutation causes a substitution of trp for arg at codon 3189 in the cytoplasmic region of the CDH23 protein (R3189W) and was predicted to affect protein-protein interaction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15537665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, THR1209ALA
|
|
</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> rs41281314 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs41281314;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/rs41281314?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=rs41281314" 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=rs41281314" 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=RCV000005210 OR RCV000039159 OR RCV000086973 OR RCV000217147 OR RCV000263856 OR RCV000787989 OR RCV002490319" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005210, RCV000039159, RCV000086973, RCV000217147, RCV000263856, RCV000787989, RCV002490319" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005210...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant, formerly titled USHER SYNDROME, TYPE ID/USHER SYNDROME, TYPE ID/F, has been reclassified based on the findings of <a href="#3" class="mim-tip-reference" title="Bell, C. J., Dinwiddie, D. L., Miller, N. A., Hateley, S. L., Ganusova, E. E., Mudge, J., Langley, R. J., Zhang, L., Lee, C. C., Schilkey, F. D., Sheth, V., Woodward, J. E., Peckham, H. E., Schroth, G. P., Kim, R. W., Kingsmore, S. F. <strong>Carrier testing for severe childhood recessive diseases by next-generation sequencing.</strong> Sci. Transl. Med. 3: 65ra4, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21228398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21228398</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21228398[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/scitranslmed.3001756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21228398">Bell et al. (2011)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21228398" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 proband with a diagnosis of Usher syndrome type I (see <a href="/entry/601067">601067</a>), <a href="#22" class="mim-tip-reference" title="Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., Liu, X. Z. <strong>Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.</strong> Hum. Molec. Genet. 14: 103-111, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15537665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15537665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15537665[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/ddi010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15537665">Zheng et al. (2005)</a> found homozygosity for an A-to-G transition at nucleotide 3625 of the CDH23 gene resulting in a thr1209 to ala substitution (T1209A), and an additional 3-bp deletion in the PCDH15 gene (<a href="/entry/605514#0005">605514.0005</a>). The authors noted that the CDH23 T1209A mutation had been found in homozygosity in a family with USH1D (<a href="#1" class="mim-tip-reference" title="Astuto, L. M., Bork, J. M., Weston, M. D., Askew, J. W., Fields, R. R., Orten, D. J., Ohliger, S. J., Riazuddin, S., Morell, R. J., Khan, S., Riazuddin, S., Kremer, H., and 15 others. <strong>CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness.</strong> Am. J. Hum. Genet. 71: 262-275, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12075507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12075507</a>] [<a href="https://doi.org/10.1086/341558" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12075507">Astuto et al., 2002</a>). The T1209A substitution is located within a linker region between extracellular repeat domains 11 and 12. <a href="#22" class="mim-tip-reference" title="Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., Liu, X. Z. <strong>Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.</strong> Hum. Molec. Genet. 14: 103-111, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15537665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15537665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15537665[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/ddi010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15537665">Zheng et al. (2005)</a> noted that their patient had a particularly severe Usher syndrome type I phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12075507+15537665" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 preconception carrier screen for 448 severe recessive childhood diseases involving 437 target genes, <a href="#3" class="mim-tip-reference" title="Bell, C. J., Dinwiddie, D. L., Miller, N. A., Hateley, S. L., Ganusova, E. E., Mudge, J., Langley, R. J., Zhang, L., Lee, C. C., Schilkey, F. D., Sheth, V., Woodward, J. E., Peckham, H. E., Schroth, G. P., Kim, R. W., Kingsmore, S. F. <strong>Carrier testing for severe childhood recessive diseases by next-generation sequencing.</strong> Sci. Transl. Med. 3: 65ra4, 2011. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21228398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21228398</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21228398[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/scitranslmed.3001756" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21228398">Bell et al. (2011)</a> found that the T1209A mutation in CDH23 is a polymorphism carried by unaffected individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21228398" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 DEAFNESS, AUTOSOMAL RECESSIVE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, PRO240LEU
|
|
</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> rs121908354 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908354;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/rs121908354?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=rs121908354" 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=rs121908354" 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=RCV000005211 OR RCV001106128 OR RCV001205177 OR RCV001261012 OR RCV001831515 OR RCV002476931 OR RCV003472978" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005211, RCV001106128, RCV001205177, RCV001261012, RCV001831515, RCV002476931, RCV003472978" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005211...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected individuals from 2 unrelated Japanese families with autosomal recessive deafness-12 (DFNB12; <a href="/entry/601386">601386</a>), <a href="#20" class="mim-tip-reference" title="Wagatsuma, M., Kitoh, R., Suzuki, H., Fukuoka, H., Takumi, Y., Usami, S. <strong>Distribution and frequencies of CDH23 mutations in Japanese patients with non-syndromic hearing loss.</strong> Clin. Genet. 72: 339-344, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17850630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17850630</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00833.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17850630">Wagatsuma et al. (2007)</a> identified compound heterozygosity for a 719C-T transition in exon 7 of the CDH23 gene, resulting in a pro240-to-leu (P240L) substitution in extracellular domain 3, and a 902G-A transition in exon 9 of the CDH23 gene, resulting in an arg301-to-gln (R301Q; <a href="#0015">605516.0015</a>) substitution in extracellular domain 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17850630" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 DEAFNESS, AUTOSOMAL RECESSIVE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, ARG301GLN
|
|
</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> rs121908355 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121908355;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/rs121908355?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=rs121908355" 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=rs121908355" 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=RCV000005212 OR RCV000173892 OR RCV001775064 OR RCV003472979 OR RCV003478971" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005212, RCV000173892, RCV001775064, RCV003472979, RCV003478971" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005212...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg301-to-gln (R301Q) mutation in the CDH23 gene that was found in compound heterozygous state in patients with autosomal recessive deafness-12 (DFNB12; <a href="/entry/601386">601386</a>) by <a href="#20" class="mim-tip-reference" title="Wagatsuma, M., Kitoh, R., Suzuki, H., Fukuoka, H., Takumi, Y., Usami, S. <strong>Distribution and frequencies of CDH23 mutations in Japanese patients with non-syndromic hearing loss.</strong> Clin. Genet. 72: 339-344, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17850630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17850630</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00833.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17850630">Wagatsuma et al. (2007)</a>, see <a href="#0014">605516.0014</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17850630" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="0016" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 PITUITARY ADENOMA 5, MULTIPLE TYPES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, ARG1379LEU
|
|
</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> rs767004225 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs767004225;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/rs767004225?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=rs767004225" 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=rs767004225" 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=RCV000504588 OR RCV003317244" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000504588, RCV003317244" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000504588...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 members of a family with pituitary adenomas (PITA5; <a href="/entry/617540">617540</a>), <a href="#21" class="mim-tip-reference" title="Zhang, Q., Peng, C., Song, J., Zhang, Y., Chen, J., Song, Z., Shou, X., Ma, Z., Peng, H., Jian, X., He, W., Ye, Z., and 22 others. <strong>Germline mutations in CDH23, encoding cadherin-related 23, are associated with both familial and sporadic pituitary adenomas.</strong> Am. J. Hum. Genet. 100: 817-823, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28413019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28413019</a>] [<a href="https://doi.org/10.1016/j.ajhg.2017.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28413019">Zhang et al. (2017)</a> identified a heterozygous c.4136G-T transversion (c.4136G-T, NM_022124.5) in the CDH23 gene, resulting in an arg1379-to-leu (R1379L) substitution at a highly conserved residue in the second calcium-binding site of the EC13 domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the 1000 Genomes Project or ExAC databases. Molecular modeling predicted that the mutation would impair calcium-binding ability and stability of the EC domain, suggesting that it is an inactivating mutation and would impair cell-cell adhesion. However, immunostaining showed that mutant CDH23 localized to the membrane of normal pituitary glands as well as pituitary adenomas, with similar expression levels as wildtype. Two patients had growth hormone-secreting adenomas and 2 had nonfunctional adenomas. Two unaffected family members also carried the mutation, but these individuals were younger than 30 years old and may still develop the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28413019" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 PITUITARY ADENOMA 5, GROWTH HORMONE-SECRETING</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, ARG2115HIS
|
|
</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> rs1270566026 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1270566026;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/rs1270566026?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=rs1270566026" 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=rs1270566026" 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=RCV000504590 OR RCV002524399" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000504590, RCV002524399" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000504590...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sisters with growth hormone-secreting pituitary adenomas (PITA5; <a href="/entry/617540">617540</a>), <a href="#21" class="mim-tip-reference" title="Zhang, Q., Peng, C., Song, J., Zhang, Y., Chen, J., Song, Z., Shou, X., Ma, Z., Peng, H., Jian, X., He, W., Ye, Z., and 22 others. <strong>Germline mutations in CDH23, encoding cadherin-related 23, are associated with both familial and sporadic pituitary adenomas.</strong> Am. J. Hum. Genet. 100: 817-823, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28413019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28413019</a>] [<a href="https://doi.org/10.1016/j.ajhg.2017.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28413019">Zhang et al. (2017)</a> identified a heterozygous c.6344G-A transition (c.6344G-A, NM_022124.5) in the CDH23 gene, resulting in an arg2115-to-his (R2115H) substitution at a highly conserved residue in 1 of the EC domains. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the 1000 Genomes Project or ExAC databases. Two unaffected family members also carried the mutation, suggesting incomplete or age-dependent penetrance. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28413019" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 PITUITARY ADENOMA 5, NONFUNCTIONAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, ARG3138TRP
|
|
</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> rs1052484950 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1052484950;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/rs1052484950?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=rs1052484950" 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=rs1052484950" 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=RCV000504591" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000504591" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000504591</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 members of a family with nonfunctional pituitary adenomas (PITA5; <a href="/entry/617540">617540</a>), <a href="#21" class="mim-tip-reference" title="Zhang, Q., Peng, C., Song, J., Zhang, Y., Chen, J., Song, Z., Shou, X., Ma, Z., Peng, H., Jian, X., He, W., Ye, Z., and 22 others. <strong>Germline mutations in CDH23, encoding cadherin-related 23, are associated with both familial and sporadic pituitary adenomas.</strong> Am. J. Hum. Genet. 100: 817-823, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28413019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28413019</a>] [<a href="https://doi.org/10.1016/j.ajhg.2017.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28413019">Zhang et al. (2017)</a> identified a heterozygous c.9412C-T transition (c.9412C-T, NM_022124.5) in the CDH23 gene, resulting in an arg3138-to-trp (R3138W) substitution at a highly conserved residue in 1 of the EC domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the 1000 Genomes Project or ExAC databases. Two unaffected family members also carried the mutation, suggesting incomplete or age-dependent penetrance. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28413019" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 PITUITARY ADENOMA 5, NONFUNCTIONAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
CDH23, ASP3296ASN
|
|
</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> rs372388344 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs372388344;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/rs372388344?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=rs372388344" 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=rs372388344" 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=RCV000504587 OR RCV001038259 OR RCV001271955" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000504587, RCV001038259, RCV001271955" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000504587...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 members of a family with nonfunctional pituitary adenomas (PITA5; <a href="/entry/617540">617540</a>), <a href="#21" class="mim-tip-reference" title="Zhang, Q., Peng, C., Song, J., Zhang, Y., Chen, J., Song, Z., Shou, X., Ma, Z., Peng, H., Jian, X., He, W., Ye, Z., and 22 others. <strong>Germline mutations in CDH23, encoding cadherin-related 23, are associated with both familial and sporadic pituitary adenomas.</strong> Am. J. Hum. Genet. 100: 817-823, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28413019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28413019</a>] [<a href="https://doi.org/10.1016/j.ajhg.2017.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28413019">Zhang et al. (2017)</a> identified a heterozygous c.9886G-A transition (c.9886G-A, NM_022124.5) in the CDH23 gene, resulting in an asp3296-to-asn (D3296N) substitution at a highly conserved residue in 1 of the EC domains. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the 1000 Genomes Project, but was found at a very low frequency in the ExAC databases. One unaffected family member also carried the mutation, suggesting incomplete or age-dependent penetrance. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28413019" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Astuto2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Astuto, L. M., Bork, J. M., Weston, M. D., Askew, J. W., Fields, R. R., Orten, D. J., Ohliger, S. J., Riazuddin, S., Morell, R. J., Khan, S., Riazuddin, S., Kremer, H., and 15 others.
|
|
<strong>CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness.</strong>
|
|
Am. J. Hum. Genet. 71: 262-275, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12075507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12075507</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12075507" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/341558" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Bahloul2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bahloul, A., Michel, V., Hardelin, J.-P., Nouaille, S., Hoos, S., Houdusse, A., England, P., Petit, C.
|
|
<strong>Cadherin-23, myosin VIIa and harmonin, encoded by Usher syndrome type I genes, for a ternary complex and interact with membrane phospholipids.</strong>
|
|
Hum. Molec. Genet. 19: 3557-3565, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20639393/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20639393</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20639393[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=20639393" 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/ddq271" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Bell2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bell, C. J., Dinwiddie, D. L., Miller, N. A., Hateley, S. L., Ganusova, E. E., Mudge, J., Langley, R. J., Zhang, L., Lee, C. C., Schilkey, F. D., Sheth, V., Woodward, J. E., Peckham, H. E., Schroth, G. P., Kim, R. W., Kingsmore, S. F.
|
|
<strong>Carrier testing for severe childhood recessive diseases by next-generation sequencing.</strong>
|
|
Sci. Transl. Med. 3: 65ra4, 2011. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21228398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21228398</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21228398[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=21228398" 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/scitranslmed.3001756" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Boeda2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Boeda, B., El-Amraoui, A., Bahloul, A., Goodyear, R., Daviet, L., Blanchard, S., Perfettini, I., Fath, K. R., Shorte, S., Reiners, J., Houdusse, A., Legrain, P., Wolfrum, U., Richardson, G., Petit, C.
|
|
<strong>Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle.</strong>
|
|
EMBO J. 21: 6689-6699, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12485990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12485990</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12485990[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=12485990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/emboj/cdf689" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Bolz2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bolz, H., von Brederlow, B., Ramirez, A., Bryda, E. C., Kutsche, K., Nothwang, H. G., Seeliger, M., Cabrera, M. C.-S., Vila, M. C., Molina, O. P., Gal, A., Kubisch, C.
|
|
<strong>Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D.</strong>
|
|
Nature Genet. 27: 108-112, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138009/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138009</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11138009" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/83667" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Bork2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bork, J. M., Peters, L. M., Riazuddin, S., Bernstein, S. L., Ahmed, Z. M., Ness, S. L., Polomeno, R., Ramesh, A., Schloss, M., Srisailpathy, C. R. S., Wayne, S., Bellman, S., and 16 others.
|
|
<strong>Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23.</strong>
|
|
Am. J. Hum. Genet. 68: 26-37, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11090341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11090341</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11090341[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=11090341" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/316954" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="de Brouwer2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
de Brouwer, A. P. M., Pennings, R. J. E., Roeters, M., Van Hauwe, P., Astuto, L. M., Hoefsloot, L. H., Huygen, P. L. M., van den Helm, B., Deutman, A. F., Bork, J. M., Kimberling, W. J., Cremers, F. P. M., Cremers, C. W. R. J., Kremer, H.
|
|
<strong>Mutations in the calcium-binding motifs of CDH23 and the 35delG mutation in GJB2 cause hearing loss in one family.</strong>
|
|
Hum. Genet. 112: 156-163, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12522556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12522556</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12522556" 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/s00439-002-0833-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Di Palma2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Di Palma, F., Holme, R. H., Bryda, E. C., Belyantseva, I. A., Pellegrino, R., Kachar, B., Steel, K. P., Noben-Trauth, K.
|
|
<strong>Mutations in Cdh23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for Usher syndrome type 1D.</strong>
|
|
Nature Genet. 27: 103-107, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11138008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11138008</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11138008" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/83660" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Hawkins2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hawkins, R. D., Lovett, M.
|
|
<strong>The developmental genetics of auditory hair cells.</strong>
|
|
Hum. Molec. Genet. 13: R289-R296, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15358736/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15358736</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15358736" 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/ddh249" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Kazmierczak2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kazmierczak, P., Sakaguchi, H., Tokita, J., Wilson-Kubalek, E. M., Milligan, R. A., Muller, U., Kachar, B.
|
|
<strong>Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells.</strong>
|
|
Nature 449: 87-91, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17805295/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17805295</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17805295" 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/nature06091" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Marres1989" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Marres, H. A. M., Cremers, C. W. R. J.
|
|
<strong>Autosomal recessive nonsyndromal profound childhood deafness in a large pedigree: audiometric features of the affected persons and the obligate carriers.</strong>
|
|
Arch. Otolaryng. Head Neck Surg. 115: 591-595, 1989.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2706105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2706105</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2706105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archotol.1989.01860290049013" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Noben-Trauth2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Noben-Trauth, K., Zheng, Q. Y., Johnson, K. R.
|
|
<strong>Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss.</strong>
|
|
Nature Genet. 35: 21-23, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12910270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12910270</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12910270[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=12910270" 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/ng1226" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Schultz2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schultz, J. M., Bhatti, R., Madeo, A. C., Turriff, A., Muskett, J. A., Zalewski, C. K., King, K. A., Ahmed, Z. M., Riazuddin, S., Ahmad, N., Hussain, Z., Qasim, M., and 12 others.
|
|
<strong>Allelic hierarchy of CDH23 mutations causing non-syndromic deafness DFNB12 or Usher syndrome USH1D in compound heterozygotes.</strong>
|
|
J. Med. Genet. 48: 767-775, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21940737/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21940737</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21940737" 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/jmedgenet-2011-100262" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Schultz2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schultz, J. M., Yang, Y., Caride, A. J., Filoteo, A. G., Penheiter, A. R., Lagziel, A., Morell, R. J., Mohiddin, S. A., Fananapazir, L., Madeo, A. C., Penniston, J. T., Griffith, A. J.
|
|
<strong>Modification of human hearing loss by plasma-membrane calcium pump PMCA2.</strong>
|
|
New Eng. J. Med. 352: 1557-1564, 2005. Note: Erratum: New Eng. J. Med. 352: 2362 only, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15829536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15829536</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15829536" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMoa043899" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Schwander2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schwander, M., Xiong, W., Tokita, J., Lelli, A., Elledge, H. M., Kazmierczak, P., Sczaniecka, A., Kolatkar, A., Wiltshire, T., Kuhn, P., Holt, J. R., Kachar, B., Tarantino, L., Muller, U.
|
|
<strong>A mouse model for nonsyndromic deafness (DFNB12) links hearing loss to defects in tip links of mechanosensory hair cells.</strong>
|
|
Proc. Nat. Acad. Sci. 106: 5252-5257, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19270079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19270079</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19270079[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=19270079" 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.0900691106" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Siemens2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Siemens, J., Kazmierczak, P., Reynolds, A., Sticker, M., Littlewood-Evans, A., Muller, U.
|
|
<strong>The Usher syndrome proteins cadherin 23 and harmonin form a complex by means of PDZ-domain interactions.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 14946-14951, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12407180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12407180</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12407180[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=12407180" 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.232579599" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Sotomayor2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sotomayor, M., Weihofen, W. A., Gaudet, R., Corey, D. P.
|
|
<strong>Structural determinants of cadherin-23 function in hearing and deafness.</strong>
|
|
Neuron 66: 85-100, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20399731/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20399731</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20399731[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=20399731" 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.neuron.2010.03.028" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Sotomayor2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sotomayor, M., Weihofen, W. A., Gaudet, R., Corey, D. P.
|
|
<strong>Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction.</strong>
|
|
Nature 492: 128-132, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23135401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23135401</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23135401[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=23135401" 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/nature11590" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="von Brederlow2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
von Brederlow, B., Bolz, H., Janecke, A., La O Cabrera, A., Rudolph, G., Lorenz, B., Schwinger, E., Gal, A.
|
|
<strong>Identification and in vitro expression of novel CDH23 mutations of patients with Usher syndrome type 1D.</strong>
|
|
Hum. Mutat. 19: 268-273, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11857743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11857743</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11857743" 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.10049" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Wagatsuma2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wagatsuma, M., Kitoh, R., Suzuki, H., Fukuoka, H., Takumi, Y., Usami, S.
|
|
<strong>Distribution and frequencies of CDH23 mutations in Japanese patients with non-syndromic hearing loss.</strong>
|
|
Clin. Genet. 72: 339-344, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17850630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17850630</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17850630" 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.1399-0004.2007.00833.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Zhang2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhang, Q., Peng, C., Song, J., Zhang, Y., Chen, J., Song, Z., Shou, X., Ma, Z., Peng, H., Jian, X., He, W., Ye, Z., and 22 others.
|
|
<strong>Germline mutations in CDH23, encoding cadherin-related 23, are associated with both familial and sporadic pituitary adenomas.</strong>
|
|
Am. J. Hum. Genet. 100: 817-823, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28413019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28413019</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28413019" 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.ajhg.2017.03.011" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Zheng2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., Liu, X. Z.
|
|
<strong>Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.</strong>
|
|
Hum. Molec. Genet. 14: 103-111, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15537665/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15537665</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15537665[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=15537665" 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/ddi010" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 06/21/2017
|
|
</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">
|
|
Ada Hamosh - updated : 1/7/2013<br>Patricia A. Hartz - updated : 4/26/2012<br>Cassandra L. Kniffin - updated : 3/19/2012<br>Patricia A. Hartz - updated : 7/26/2011<br>Cassandra L. Kniffin - updated : 8/7/2009<br>Cassandra L. Kniffin - updated : 1/8/2008<br>George E. Tiller - updated : 10/31/2007<br>Ada Hamosh - updated : 10/16/2007<br>George E. Tiller - updated : 4/5/2007<br>Victor A. McKusick - updated : 10/26/2006<br>Victor A. McKusick - updated : 4/21/2005<br>Victor A. McKusick - updated : 8/21/2003<br>Patricia A. Hartz - updated : 3/10/2003<br>Victor A. McKusick - updated : 1/23/2003<br>Victor A. McKusick - updated : 12/10/2002<br>Victor A. McKusick - updated : 8/16/2002<br>Victor A. McKusick - updated : 4/4/2002<br>Victor A. McKusick - updated : 1/23/2001
|
|
</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 : 1/2/2001
|
|
</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 : 09/27/2017
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 09/26/2017<br>carol : 09/01/2017<br>carol : 09/01/2017<br>ckniffin : 06/21/2017<br>carol : 10/04/2016<br>carol : 07/16/2015<br>mcolton : 7/2/2015<br>carol : 8/16/2013<br>terry : 4/4/2013<br>alopez : 1/7/2013<br>terry : 1/7/2013<br>mgross : 5/2/2012<br>mgross : 5/2/2012<br>mgross : 5/2/2012<br>terry : 4/26/2012<br>alopez : 3/22/2012<br>terry : 3/19/2012<br>ckniffin : 3/19/2012<br>carol : 2/29/2012<br>mgross : 8/8/2011<br>terry : 7/26/2011<br>carol : 5/5/2011<br>alopez : 4/6/2011<br>wwang : 12/3/2010<br>wwang : 8/28/2009<br>ckniffin : 8/7/2009<br>alopez : 3/18/2008<br>alopez : 3/18/2008<br>wwang : 1/28/2008<br>ckniffin : 1/8/2008<br>alopez : 11/6/2007<br>terry : 10/31/2007<br>alopez : 10/18/2007<br>alopez : 10/18/2007<br>terry : 10/16/2007<br>alopez : 4/17/2007<br>terry : 4/5/2007<br>alopez : 10/27/2006<br>terry : 10/26/2006<br>tkritzer : 4/28/2005<br>terry : 4/21/2005<br>alopez : 9/2/2003<br>alopez : 8/22/2003<br>terry : 8/21/2003<br>tkritzer : 5/7/2003<br>mgross : 3/13/2003<br>mgross : 3/13/2003<br>terry : 3/10/2003<br>carol : 3/10/2003<br>tkritzer : 1/27/2003<br>terry : 1/23/2003<br>carol : 12/10/2002<br>tkritzer : 12/6/2002<br>terry : 12/4/2002<br>tkritzer : 8/23/2002<br>tkritzer : 8/21/2002<br>terry : 8/16/2002<br>cwells : 4/15/2002<br>cwells : 4/9/2002<br>terry : 4/4/2002<br>carol : 12/7/2001<br>carol : 3/30/2001<br>carol : 1/23/2001<br>carol : 1/23/2001<br>terry : 1/23/2001<br>mgross : 1/3/2001<br>mgross : 1/2/2001
|
|
</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> 605516
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
CADHERIN 23; CDH23
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
OTOCADHERIN<br />
|
|
CADHERIN-RELATED FAMILY, MEMBER 23; CDHR23
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: CDH23</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 10q22.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 10:71,396,920-71,815,947 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="4">
|
|
<span class="mim-font">
|
|
10q22.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
{Pituitary adenoma 5, multiple types}
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
617540
|
|
</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">
|
|
Deafness, autosomal recessive 12
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
601386
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Usher syndrome, type 1D
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
601067
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive; Digenic recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Usher syndrome, type 1D/F digenic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
601067
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive; Digenic recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The CDH23 gene encodes a member of the cadherin superfamily, which comprises calcium-dependent cell-cell adhesion glycoproteins (summary by Zhang et al., 2017). </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>Mouse chromosome 10 harbors several loci associated with hearing loss, including waltzer (v), modifier of deaf waddler (mdfw), and age-related hearing loss (Ahl). The orthologous human chromosomal region is 10q21-q22, which contains the human deafness loci DFNB12 (601386) and USH1D (601067). Di Palma et al. (2001) identified the Cdh23 gene as that mutated in waltzer mice. The 10.5-kb Cdh23 cDNA encodes a large, single-pass transmembrane protein that Di Palma et al. (2001) referred to as otocadherin. Cdh23 has an extracellular domain containing 27 repeats that show significant homology to the cadherin ectodomain. </p><p>Bolz et al. (2001) found that the CDH23 gene encodes a predicted protein of 3,354 amino acids with a single transmembrane domain and 27 cadherin repeats. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The CDH23 gene contains 69 exons (Wagatsuma et al., 2007). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Siemens et al. (2002) showed that CDH23 and harmonin (605242), another protein that is the site of mutations causing Usher syndrome, form a protein complex. Two PDZ domains in harmonin interact with 2 complementary binding surfaces in the CDH23 cytoplasmic domain. One of the binding surfaces is disrupted by sequences encoded by an alternatively spliced CDH23 exon that is expressed in the ear, but not in the retina. In the ear, CDH23 and harmonin are expressed in the stereocilia of hair cells, and in the retina within the photoreceptor cell layer. Because Cdh23-deficient mice have splayed stereocilia, Siemens et al. (2002) suggested that CDH23 and harmonin are part of a transmembrane complex that connects stereocilia into a bundle, and that defects in the formation of this complex may disrupt stereocilia bundles and cause deafness in patients with Usher syndrome type I. </p><p>Boeda et al. (2002) noted that 3 distinct genetic forms of Usher syndrome are caused by defects in the CDH23, harmonin, and MYO7A (276903) genes. They observed severely disorganized hair bundles in shaker-1 mice, which carry a mutation in the Myo7a gene. Immunohistochemical analysis of differentiating hair cells indicated that Cdh23 was distributed normally, but harmonin b was not. Using human and mouse cDNA constructs and cells, they confirmed interaction between harmonin and CDH23 in vitro and in vivo. They also provided evidence that harmonin b anchors CDH23 to the stereocilia microfilaments and interacts directly with MYO7A, which conveys harmonin b along the actin core of the developing stereocilia. Boeda et al. (2002) proposed that the shaping of the hair bundle relies on a functional unit composed of MYO7A, harmonin b, and CDH23 and that the interaction of these proteins ensures the cohesion of the stereocilia. </p><p>Hawkins and Lovett (2004) reviewed the developmental genetics of auditory hair cells. </p><p>Kazmierczak et al. (2007) demonstrated that CDH23 and PCDH15 (605514), 2 cadherins that are linked to inherited forms of deafness in humans, interact to form tip links, extracellular filaments that connect the stereocilia and are thought to gate the mechanoelectrical transduction channel. Immunohistochemical studies using rodent hair cells showed that CDH23 and PCDH15 localized to the upper and lower part of tip links, respectively. The amino termini of the 2 cadherins colocalized on tip link filaments. Biochemical experiments showed that CDH23 homodimers interact in trans with PCDH15 homodimers to form a filament with structural similarity to tip links. Ions that affected tip link integrity and a mutation in PCDH15 that causes a recessive form of deafness (see DFNB23, 609533) disrupted interactions between CDH23 and PCDH15. Kazmierczak et al. (2007) concluded that their studies defined the molecular composition of tip links and provided a conceptual base for exploring the mechanisms of sensory impairment associated with mutations in CDH23 and PCDH15. </p><p>Using molecular dynamic simulations, Sotomayor et al. (2010) found that the first 2 extracellular cadherin (EC) repeats of mouse Cdh23 were relatively stiff and required binding of 3 Ca(2+) ions at the linker region for mechanical integrity. Sotomayor et al. (2010) predicted that mutations in CDH23 that alter Ca(2+) binding could affect bending between the EC repeats, particularly at lower Ca(2+) concentrations, and alter the function of the stereocilia tip links. They proposed that lack of vestibular phenotypes in some Cdh23 mutant mice and DFNB12 patients may be due to the higher Ca(2+) concentration in vestibular endolymph compared with cochlear endolymph. </p><p>Bahloul et al. (2010) found that isoforms of mouse Cdh23 that either included or excluded an exon 68-encoded sequence bound directly to the harmonin A isoform and to the tail of myosin-7a. The 3 proteins formed a complex that interacted with phosphatidylinositol 4,5-bisphosphate in synthetic liposomes. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
Sotomayor et al. (2012) combined crystallography, molecular dynamics simulations, and binding experiments to characterize the protocadherin-15 (605514)-cadherin-23 bond. They found a unique cadherin interaction mechanism in which the 2 most N-terminal cadherin repeats (extracellular cadherin repeats 1 and 2) of each protein interact to form an overlapped, antiparallel heterodimer. Simulations predicted that this tip-link bond is mechanically strong enough to resist forces in hair cells. In addition, the complex was shown to become unstable in response to calcium removal owing to increased flexure of calcium-free cadherin repeats. Finally, Sotomayor et al. (2012) used structures and biochemical measurements to study the molecular mechanisms by which deafness mutations disrupt tip-link function. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Usher Syndrome Type ID</em></strong></p><p>
|
|
Bolz et al. (2001) identified a Cuban pedigree in which type I Usher syndrome was linked to the USH1D locus on chromosome 10 (see 601067). Affected individuals presented with congenital deafness and a highly variable degree of retinal degeneration as an autosomal recessive trait. Using a positional candidate approach, Bolz et al. (2001) identified CDH23 as the gene responsible for USH1D in these individuals. In the Cuban family, the authors detected 2 different CDH23 mutations. A severe course of the retinal disease was observed in individuals homozygous for a presumed truncating splice site mutation (605516.0001), whereas mild retinitis pigmentosa was present in individuals carrying a homozygous missense mutation (605516.0002). Variable expression of the retinal phenotype was seen in patients with a combination of the 2 mutations. Bolz et al. (2001) also identified 2 mutations in the CDH23 gene in a German patient with Usher syndrome (605516.0003-605516.0004). </p><p>Simultaneously and independently, Bork et al. (2001) identified 2 nonsense and 2 frameshift mutations in the CDH23 gene (see, e.g., 605516.0007) in 4 families with USH1D. </p><p>In 33 patients with type I Usher syndrome in whom USH1B (276903) and USH1C (605242) had been excluded, von Brederlow et al. (2002) performed mutation screening by single-strand conformation polymorphism (SSCP) analysis and direct sequencing. On 8 disease alleles of 4 patients, 4 different mutations in the CDH23 gene were identified, 3 of them being novel. Among a total of 52 type I Usher cases studied by this group, CDH23 mutations accounted for about 10% of all disease alleles. </p><p>Only missense mutations of CDH23 have been observed in families with nonsyndromic deafness, whereas nonsense, frameshift, splice-site, and missense mutations have been identified in families with Usher syndrome. Astuto et al. (2002) screened a panel of 69 probands with Usher syndrome and 38 probands with recessive nonsyndromic deafness for the presence of mutations in the entire coding region of CDH23, by heteroduplex, SSCP, and direct sequence analyses. Thirty-six different CDH23 mutations were detected in 45 families; 33 of these mutations were novel, including 18 missense, 3 nonsense, 5 splicing defects, 5 microdeletions, and 2 insertions. Seven mutations were common to more than 1 family. Ophthalmologic examination of patients with nonsyndromic deafness revealed asymptomatic manifestations similar to retinitis pigmentosa (RP; 268000), which indicated that missense mutations may have a subtle effect in the retina. Furthermore, patients with mutations in CDH23 displayed a wide range of hearing loss and RP phenotypes, differing in severity, age at onset, type, and the presence or absence of vestibular areflexia. Astuto et al. (2002) also presented a comprehensive catalog of CDH23 mutations identified both in their study and in patients reported elsewhere with either recessive nonsyndromic deafness or Usher syndrome type I. </p><p><strong><em>Autosomal Recessive Deafness 12</em></strong></p><p>
|
|
In 5 families segregating autosomal recessive nonsyndromic hearing loss (DFNB12; 601386), Bork et al. (2001) identified 6 missense mutations in the CDH23 gene (see, e.g., 605516.0005-605516.0006). </p><p>In 5 sibs, born of consanguineous parents, with autosomal recessive deafness, Schultz et al. (2005) identified a homozygous phe1888-to-ser substitution in the CDH23 gene (F1888S; 605516.0010). Two of the sibs had high frequency hearing loss and 3 had severe to profound hearing loss affecting all frequencies. The 3 severely affected sibs were additionally heterozygous for a val586-to-met substitution in the ATP2B2 gene (V586M; 108733.0001). </p><p>Wagatsuma et al. (2007) identified homozygosity or compound heterozygosity for 4 different missense mutations in the CDH23 gene (see, e.g., 605516.0014 and 605516.0015) in 6 Japanese patients from 5 families with autosomal recessive hearing loss. All four mutations were in the extracellular domain of the protein. The findings indicated that mutations in the CDH23 gene may account for about 5% of nonsyndromic hearing loss in the Japanese population. </p><p><strong><em>Usher Syndrome Type ID/F</em></strong></p><p>
|
|
Zheng et al. (2005) reported 3 families with Usher syndrome type I in which affected members carried mutations in both CDH23 and PCDH15 (605514), thus supporting a digenic model for some individuals with this phenotype. Based on an animal model, the authors concluded that CDH23 and PCDH15 play an essential long-term role in maintaining the normal organization of the stereocilia bundle. </p><p><strong><em>Pituitary Adenoma 5, Susceptibility to</em></strong></p><p>
|
|
In affected members of 4 unrelated families with both functional GH-secreting and nonfunctional pituitary adenomas (PITA5; 617540), Zhang et al. (2017) identified germline heterozygous missense mutations in the CDH23 gene (605516.0016-605516.0019). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. There was evidence of age-dependent or incomplete penetrance. Whole-exome sequencing of 125 individuals with sporadic pituitary adenomas identified CDH23 mutations in 15 individuals (12.0%); 13 had heterozygous mutations and 2 had homozygous mutations. The tumor types in these patients varied. All mutations identified occurred at highly conserved residues in the EC domains of CDH23 and were predicted to adversely affect calcium binding or protein folding. Functional studies of the variants were not performed. Compared to pituitary adenomas with wildtype CDH23, those associated with CDH23 mutations were smaller in diameter and less invasive. Heterozygous, putatively functional variants in the CDH23 gene were found in 2 (0.8%) of 260 control individuals. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>DFNB12 is associated with CDH23 missense mutations that are presumed to be hypomorphic alleles with sufficient residual activity for retinal and vestibular function, but not for auditory cochlear function. In contrast, homozygous nonsense, frameshift, splice site, and some missense mutations of CDH23, or a combination of these USH1D alleles in a compound heterozygote, cause USH1D. Schultz et al. (2011) identified 12 different homozygous CDH23 mutations, including 8 novel mutations, in 13 families with DFNB12. All were missense, except 1 in-frame deletion. Ten different homozygous mutations were found in 14 families and 1 singleton with USH1D. These latter mutations were mostly nonsense, frameshift, or splice site mutations, but there was 1 in-frame deletion and 2 missense mutations. Affected individuals in 3 additional families were found to carry compound heterozygous mutations in the CDH23 gene, with the different alleles being associated with either DFNB12 or USH1D. Based on the phenotypes within families, the results indicated that USH1D occurs only when there are 2 USH1D alleles in trans. In contrast, when there is a DFNB12 allele in trans with a USH1D allele, the phenotype is DFNB12. The findings indicated that a DFNB12 allele is phenotypically dominant to a USH1D allele, and can preserve normal retinal and vestibular function even in the presence of a USH1D allele. Schultz et al. (2011) noted the implications for genetic counseling. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Di Palma et al. (2001) identified loss-of-function mutations in the Cdh23 gene in each of 3 different waltzer alleles. They demonstrated that Cdh23 is expressed in the neurosensory epithelium. During early hair cell differentiation, stereocilia organization was disrupted in homozygotes for one of the mutant alleles. The data indicated that Cdh23 is a critical component of hair bundle formation. The demonstration of mutations in the human CDH23 gene in USH1D established waltzer as the mouse model for USH1D. </p><p>Age-related hearing loss (AHL) in common inbred mouse strains is a genetically complex quantitative trait. Noben-Trauth et al. (2003) found a synonymous single-nucleotide polymorphism (SNP) in exon 7 of the Cdh23 gene that showed significant association with AHL and the deafness modifier mdfw (modifier of deafwaddler). The hypomorphic Cdh23(753A) allele caused in-frame skipping of exon 7. Altered adhesion or reduced stability of CDH23 may confer susceptibility to AHL. Homozygosity at Cdh23(753A) or in combination with heterogeneous secondary factors was found to be a primary determinant of AHL in mice. </p><p>Zheng et al. (2005) generated mice that were heterozygous for both Cdh23(v-2J) and Pcdh15(av-3J) (605514) mutations on a uniform C57BL/6J background. Significant levels of hearing loss were detected in these mice when compared to age-matched single heterozygous animals or normal controls, which supported a digenic model of hearing loss. Cytoarchitectural defects in the cochlea of digenic heterozygotes, including degeneration of the stereocilia and a base-apex loss of hair cells and spiral ganglion cells, were consistent with the observed age-related hearing loss of these mice beginning with the high frequencies. The authors noted that while hearing loss was progressive in these animals, humans with heterozygosity for both CDH23 and PCDH15 mutations are congenitally deaf. Zheng et al. (2005) concluded that CDH23 and PCDH15 play an essential long-term role in maintaining the normal organization of the stereocilia bundle. </p><p>In an N-ethyl-N-nitrosourea (ENU) mutagenesis screen, Schwander et al. (2009) identified 'salsa' mice, which suffer from progressive hearing loss and carry a Cdh23 mutation (E737V) that is predicted to affect Ca(2+) binding by the extracellular domain. Otoacoustic emissions were not detected, suggesting a defect in outer hair cell function. Similar mutations in the human CDH23 gene cause DFNB12. Although hair bundle development appeared unaffected in salsa mice, tip links were progressively lost, resulting in hair cell death. Tip links in vestibular hair cells were unaffected. Biochemical studies showed that mutant Cdh23 had impaired interaction with Pcdh15. The findings suggested that missense mutations in DFNB12 patients lead to deafness by affecting tip links. </p><p>Bahloul et al. (2010) found that knockout of Cdh23 in mice resulted in loss of harmonin from the apex of hair bundles in the organ of Corti and caused redistribution of a weakened myosin-7a signal along stereocilia. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>19 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 USHER SYNDROME, TYPE ID</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, GLN1496HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908347,
|
|
|
|
|
|
|
|
ClinVar: RCV000005197, RCV001566890, RCV001835621, RCV003472971
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Cuban family with Usher syndrome type ID (USH1D; 601067), Bolz et al. (2001) identified a G-to-C transversion at nucleotide 4488 of the CDH23 gene, leading to a gln1496-to-his (Q1496H) mutation. The mutation resulted in aberrant splicing in an in vitro assay. Homozygotes for this mutation had a severe course of retinal disease. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 USHER SYNDROME, TYPE ID</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, ARG1746GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs111033270,
|
|
|
|
|
|
gnomAD: rs111033270,
|
|
|
|
|
|
ClinVar: RCV000005198, RCV000254732, RCV000763215, RCV000844622, RCV001073594, RCV001274889, RCV001328020, RCV002222340, RCV002272010, RCV002512799, RCV003472972, RCV004528082
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Cuban family with Usher syndrome type ID (USH1D; 601067), Bolz et al. (2001) identified a G-to-A transition at nucleotide 5237 of the CDH23 gene, resulting in an arg1746-to-gln (R1746Q) mutation. Homozygotes for this mutation had mild retinitis pigmentosa. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 USHER SYNDROME, TYPE ID</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, 3-BP DEL, 3841ATG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs796051860,
|
|
|
|
|
|
|
|
ClinVar: RCV000005199, RCV005089176
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a German patient with Usher syndrome type ID (USH1D; 601067), Bolz et al. (2001) identified compound heterozygosity for 2 mutations in the CDH23 gene: a 3-bp deletion at nucleotide 3841, resulting in the deletion of met1281, and a G-to-A transition at the +5 position of intron 51 (605516.0004). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 USHER SYNDROME, TYPE ID</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, IVS51, G-A, +5
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs727502931,
|
|
|
|
|
|
gnomAD: rs727502931,
|
|
|
|
|
|
ClinVar: RCV000005200, RCV000844693, RCV001851662, RCV003472973
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the G-to-A transition at the +5 position of intron 51 in the CDH23 gene that was found in compound heterozygous state in a patient with Usher syndrome type ID (USH1D; 601067) by Bolz et al. (2001), see 605516.0003. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 DEAFNESS, AUTOSOMAL RECESSIVE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, ASP1243ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908348,
|
|
|
|
|
|
gnomAD: rs121908348,
|
|
|
|
|
|
ClinVar: RCV000005201, RCV001291217, RCV003472974
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with autosomal recessive deafness-12 (DFNB12; 601386), Bork et al. (2001) identified an asp1243-to-asn (D1243N) mutation in the CDH23 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 DEAFNESS, AUTOSOMAL RECESSIVE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, ASP1400ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908349,
|
|
|
|
|
|
gnomAD: rs121908349,
|
|
|
|
|
|
ClinVar: RCV000005202, RCV000818407, RCV001291219, RCV001831514, RCV003387716, RCV003472975, RCV005041985
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with autosomal recessive deafness-12 (DFNB12; 601386), Bork et al. (2001) found that affected members had an asp1400-to-asn (D1400N) mutation in the CDH23 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 USHER SYNDROME, TYPE ID</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, GLN492TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908350,
|
|
|
|
|
|
|
|
ClinVar: RCV000005203, RCV001291211, RCV001386699
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with Usher syndrome type ID (USHID; 601067), Bork et al. (2001) found that affected members had a gln492-to-ter (Q492X) mutation in the CDH23 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 DEAFNESS, AUTOSOMAL RECESSIVE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, ASP2148ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs111033271,
|
|
|
|
|
|
gnomAD: rs111033271,
|
|
|
|
|
|
ClinVar: RCV000005204, RCV000599622, RCV000710063, RCV000809058, RCV001826421, RCV003472976, RCV003987312, RCV004757097, RCV004783719, RCV004814828, RCV005041986
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 presumably unrelated families with autosomal recessive nonsyndromic deafness mapping to chromosome 10q (DFNB12; 601386), Astuto et al. (2002) found an asp2148-to-asn (D2148N) mutation in the CDH23 gene, located in exon 47 in extracellular domain 20. </p><p>De Brouwer et al. (2003) performed a genetic analysis of a large consanguineous family with DFNB12 that was previously described by Marres and Cremers (1989). Patients in 1 branch of the family were homozygous for the 35delG mutation in the GJB2 gene (121011.0005) causing DFNB1 (220290). Patients in 2 other branches carried 2 novel mutations in the CDH23 gene causing DFNB12: a homozygous 6442G-A transition in exon 47 causing the D2148N mutation in 1 branch, and compound heterozygosity for this mutation and a 4021G-A transition causing an asp1341-to-asn (D1341N) mutation (605516.0009). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 DEAFNESS, AUTOSOMAL RECESSIVE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, ASP1341ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908351,
|
|
|
|
|
|
gnomAD: rs121908351,
|
|
|
|
|
|
ClinVar: RCV000005205, RCV000436619, RCV001272891, RCV003472977, RCV003492284
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the asp1341-to-asn (D1341N) mutation in the CDH23 gene that was found in compound heterozygous state in patients with autosomal recessive deafness-12 (DFNB12; 601386) by de Brouwer et al. (2003), see 605516.0008. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 DEAFNESS, AUTOSOMAL RECESSIVE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, PHE1888SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908352,
|
|
|
|
|
|
|
|
ClinVar: RCV000005206, RCV001851663
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 sibs, born of consanguineous parents, with autosomal recessive deafness-12 (DFNB12; 601386), Schultz et al. (2005) identified a homozygous 5663T-C transition in exon 42 of the CDH23 gene, resulting in a phe1888-to-ser (F1888S) substitution in the extracellular domain of the protein. Two of the sibs had high frequency hearing loss and 3 had severe to profound hearing loss affecting all frequencies. The 3 severely affected sibs were heterozygous for a val586-to-met substitution in the ATP2B2 gene (V586M; 108733.0001). Variants in ATP2B2, the plasma membrane calcium pump, modulate the severity of hearing loss in mice with mutations in the CDH23 gene (Noben-Trauth et al., 2003). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 USHER SYNDROME, TYPE ID</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
USHER SYNDROME, TYPE ID/F, DIGENIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, 1-BP DEL, 193C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs796051861,
|
|
|
|
|
|
|
|
ClinVar: RCV000005207, RCV000005208, RCV000215123, RCV000254862, RCV005041987
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a proband with a diagnosis of Usher syndrome type I (see 601067), Zheng et al. (2005) found compound heterozygosity for a 1-bp deletion of the CDH23 gene, 193delC, and a 3-bp deletion in the PCDH15 gene (605514.0005). The 193delC mutation was previously found in a patient with Usher syndrome type ID (USH1D) by Astuto et al. (2002). The CDH23 193delC mutation consists of deletion of a single C in a CCCCC string in exon 3, which causes a frameshift at codon 65 in the first extracellular repeat domain and a stop codon 48 amino acids downstream. The resulting truncated protein lacked approximately 96% of the predicted coding sequence. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 USHER SYNDROME, TYPE ID/F, DIGENIC</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, ARG3189TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908353,
|
|
|
|
|
|
gnomAD: rs121908353,
|
|
|
|
|
|
ClinVar: RCV000005209, RCV000039312, RCV000222140, RCV000787978, RCV001358062, RCV002482830
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a proband with a diagnosis of Usher syndrome type I (see 601067), Zheng et al. (2005) found compound heterozygosity for a C-to-T transition at nucleotide 9565 of the CDH23 gene and a 1-bp deletion in the PCDH15 gene (16delT; 605514.0008). The 9565C-T mutation causes a substitution of trp for arg at codon 3189 in the cytoplasmic region of the CDH23 protein (R3189W) and was predicted to affect protein-protein interaction. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, THR1209ALA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs41281314,
|
|
|
|
|
|
gnomAD: rs41281314,
|
|
|
|
|
|
ClinVar: RCV000005210, RCV000039159, RCV000086973, RCV000217147, RCV000263856, RCV000787989, RCV002490319
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant, formerly titled USHER SYNDROME, TYPE ID/USHER SYNDROME, TYPE ID/F, has been reclassified based on the findings of Bell et al. (2011). </p><p>In a proband with a diagnosis of Usher syndrome type I (see 601067), Zheng et al. (2005) found homozygosity for an A-to-G transition at nucleotide 3625 of the CDH23 gene resulting in a thr1209 to ala substitution (T1209A), and an additional 3-bp deletion in the PCDH15 gene (605514.0005). The authors noted that the CDH23 T1209A mutation had been found in homozygosity in a family with USH1D (Astuto et al., 2002). The T1209A substitution is located within a linker region between extracellular repeat domains 11 and 12. Zheng et al. (2005) noted that their patient had a particularly severe Usher syndrome type I phenotype. </p><p>In a preconception carrier screen for 448 severe recessive childhood diseases involving 437 target genes, Bell et al. (2011) found that the T1209A mutation in CDH23 is a polymorphism carried by unaffected individuals. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 DEAFNESS, AUTOSOMAL RECESSIVE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, PRO240LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908354,
|
|
|
|
|
|
gnomAD: rs121908354,
|
|
|
|
|
|
ClinVar: RCV000005211, RCV001106128, RCV001205177, RCV001261012, RCV001831515, RCV002476931, RCV003472978
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected individuals from 2 unrelated Japanese families with autosomal recessive deafness-12 (DFNB12; 601386), Wagatsuma et al. (2007) identified compound heterozygosity for a 719C-T transition in exon 7 of the CDH23 gene, resulting in a pro240-to-leu (P240L) substitution in extracellular domain 3, and a 902G-A transition in exon 9 of the CDH23 gene, resulting in an arg301-to-gln (R301Q; 605516.0015) substitution in extracellular domain 3. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 DEAFNESS, AUTOSOMAL RECESSIVE 12</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, ARG301GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121908355,
|
|
|
|
|
|
gnomAD: rs121908355,
|
|
|
|
|
|
ClinVar: RCV000005212, RCV000173892, RCV001775064, RCV003472979, RCV003478971
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg301-to-gln (R301Q) mutation in the CDH23 gene that was found in compound heterozygous state in patients with autosomal recessive deafness-12 (DFNB12; 601386) by Wagatsuma et al. (2007), see 605516.0014. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 PITUITARY ADENOMA 5, MULTIPLE TYPES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, ARG1379LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs767004225,
|
|
|
|
|
|
gnomAD: rs767004225,
|
|
|
|
|
|
ClinVar: RCV000504588, RCV003317244
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 members of a family with pituitary adenomas (PITA5; 617540), Zhang et al. (2017) identified a heterozygous c.4136G-T transversion (c.4136G-T, NM_022124.5) in the CDH23 gene, resulting in an arg1379-to-leu (R1379L) substitution at a highly conserved residue in the second calcium-binding site of the EC13 domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the 1000 Genomes Project or ExAC databases. Molecular modeling predicted that the mutation would impair calcium-binding ability and stability of the EC domain, suggesting that it is an inactivating mutation and would impair cell-cell adhesion. However, immunostaining showed that mutant CDH23 localized to the membrane of normal pituitary glands as well as pituitary adenomas, with similar expression levels as wildtype. Two patients had growth hormone-secreting adenomas and 2 had nonfunctional adenomas. Two unaffected family members also carried the mutation, but these individuals were younger than 30 years old and may still develop the disorder. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 PITUITARY ADENOMA 5, GROWTH HORMONE-SECRETING</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, ARG2115HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1270566026,
|
|
|
|
|
|
gnomAD: rs1270566026,
|
|
|
|
|
|
ClinVar: RCV000504590, RCV002524399
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 sisters with growth hormone-secreting pituitary adenomas (PITA5; 617540), Zhang et al. (2017) identified a heterozygous c.6344G-A transition (c.6344G-A, NM_022124.5) in the CDH23 gene, resulting in an arg2115-to-his (R2115H) substitution at a highly conserved residue in 1 of the EC domains. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the 1000 Genomes Project or ExAC databases. Two unaffected family members also carried the mutation, suggesting incomplete or age-dependent penetrance. Functional studies of the variant and studies of patient cells were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 PITUITARY ADENOMA 5, NONFUNCTIONAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, ARG3138TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1052484950,
|
|
|
|
|
|
gnomAD: rs1052484950,
|
|
|
|
|
|
ClinVar: RCV000504591
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 members of a family with nonfunctional pituitary adenomas (PITA5; 617540), Zhang et al. (2017) identified a heterozygous c.9412C-T transition (c.9412C-T, NM_022124.5) in the CDH23 gene, resulting in an arg3138-to-trp (R3138W) substitution at a highly conserved residue in 1 of the EC domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the 1000 Genomes Project or ExAC databases. Two unaffected family members also carried the mutation, suggesting incomplete or age-dependent penetrance. Functional studies of the variant and studies of patient cells were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 PITUITARY ADENOMA 5, NONFUNCTIONAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
CDH23, ASP3296ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs372388344,
|
|
|
|
|
|
gnomAD: rs372388344,
|
|
|
|
|
|
ClinVar: RCV000504587, RCV001038259, RCV001271955
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 members of a family with nonfunctional pituitary adenomas (PITA5; 617540), Zhang et al. (2017) identified a heterozygous c.9886G-A transition (c.9886G-A, NM_022124.5) in the CDH23 gene, resulting in an asp3296-to-asn (D3296N) substitution at a highly conserved residue in 1 of the EC domains. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not found in the 1000 Genomes Project, but was found at a very low frequency in the ExAC databases. One unaffected family member also carried the mutation, suggesting incomplete or age-dependent penetrance. Functional studies of the variant and studies of patient cells were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Astuto, L. M., Bork, J. M., Weston, M. D., Askew, J. W., Fields, R. R., Orten, D. J., Ohliger, S. J., Riazuddin, S., Morell, R. J., Khan, S., Riazuddin, S., Kremer, H., and 15 others.
|
|
<strong>CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness.</strong>
|
|
Am. J. Hum. Genet. 71: 262-275, 2002.
|
|
|
|
|
|
[PubMed: 12075507]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/341558]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bahloul, A., Michel, V., Hardelin, J.-P., Nouaille, S., Hoos, S., Houdusse, A., England, P., Petit, C.
|
|
<strong>Cadherin-23, myosin VIIa and harmonin, encoded by Usher syndrome type I genes, for a ternary complex and interact with membrane phospholipids.</strong>
|
|
Hum. Molec. Genet. 19: 3557-3565, 2010.
|
|
|
|
|
|
[PubMed: 20639393]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddq271]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bell, C. J., Dinwiddie, D. L., Miller, N. A., Hateley, S. L., Ganusova, E. E., Mudge, J., Langley, R. J., Zhang, L., Lee, C. C., Schilkey, F. D., Sheth, V., Woodward, J. E., Peckham, H. E., Schroth, G. P., Kim, R. W., Kingsmore, S. F.
|
|
<strong>Carrier testing for severe childhood recessive diseases by next-generation sequencing.</strong>
|
|
Sci. Transl. Med. 3: 65ra4, 2011. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 21228398]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/scitranslmed.3001756]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Boeda, B., El-Amraoui, A., Bahloul, A., Goodyear, R., Daviet, L., Blanchard, S., Perfettini, I., Fath, K. R., Shorte, S., Reiners, J., Houdusse, A., Legrain, P., Wolfrum, U., Richardson, G., Petit, C.
|
|
<strong>Myosin VIIa, harmonin and cadherin 23, three Usher I gene products that cooperate to shape the sensory hair cell bundle.</strong>
|
|
EMBO J. 21: 6689-6699, 2002.
|
|
|
|
|
|
[PubMed: 12485990]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/emboj/cdf689]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bolz, H., von Brederlow, B., Ramirez, A., Bryda, E. C., Kutsche, K., Nothwang, H. G., Seeliger, M., Cabrera, M. C.-S., Vila, M. C., Molina, O. P., Gal, A., Kubisch, C.
|
|
<strong>Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D.</strong>
|
|
Nature Genet. 27: 108-112, 2001.
|
|
|
|
|
|
[PubMed: 11138009]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/83667]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bork, J. M., Peters, L. M., Riazuddin, S., Bernstein, S. L., Ahmed, Z. M., Ness, S. L., Polomeno, R., Ramesh, A., Schloss, M., Srisailpathy, C. R. S., Wayne, S., Bellman, S., and 16 others.
|
|
<strong>Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23.</strong>
|
|
Am. J. Hum. Genet. 68: 26-37, 2001.
|
|
|
|
|
|
[PubMed: 11090341]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/316954]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
de Brouwer, A. P. M., Pennings, R. J. E., Roeters, M., Van Hauwe, P., Astuto, L. M., Hoefsloot, L. H., Huygen, P. L. M., van den Helm, B., Deutman, A. F., Bork, J. M., Kimberling, W. J., Cremers, F. P. M., Cremers, C. W. R. J., Kremer, H.
|
|
<strong>Mutations in the calcium-binding motifs of CDH23 and the 35delG mutation in GJB2 cause hearing loss in one family.</strong>
|
|
Hum. Genet. 112: 156-163, 2003.
|
|
|
|
|
|
[PubMed: 12522556]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-002-0833-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Di Palma, F., Holme, R. H., Bryda, E. C., Belyantseva, I. A., Pellegrino, R., Kachar, B., Steel, K. P., Noben-Trauth, K.
|
|
<strong>Mutations in Cdh23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for Usher syndrome type 1D.</strong>
|
|
Nature Genet. 27: 103-107, 2001.
|
|
|
|
|
|
[PubMed: 11138008]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/83660]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hawkins, R. D., Lovett, M.
|
|
<strong>The developmental genetics of auditory hair cells.</strong>
|
|
Hum. Molec. Genet. 13: R289-R296, 2004.
|
|
|
|
|
|
[PubMed: 15358736]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddh249]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kazmierczak, P., Sakaguchi, H., Tokita, J., Wilson-Kubalek, E. M., Milligan, R. A., Muller, U., Kachar, B.
|
|
<strong>Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cells.</strong>
|
|
Nature 449: 87-91, 2007.
|
|
|
|
|
|
[PubMed: 17805295]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature06091]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Marres, H. A. M., Cremers, C. W. R. J.
|
|
<strong>Autosomal recessive nonsyndromal profound childhood deafness in a large pedigree: audiometric features of the affected persons and the obligate carriers.</strong>
|
|
Arch. Otolaryng. Head Neck Surg. 115: 591-595, 1989.
|
|
|
|
|
|
[PubMed: 2706105]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archotol.1989.01860290049013]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Noben-Trauth, K., Zheng, Q. Y., Johnson, K. R.
|
|
<strong>Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss.</strong>
|
|
Nature Genet. 35: 21-23, 2003.
|
|
|
|
|
|
[PubMed: 12910270]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1226]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schultz, J. M., Bhatti, R., Madeo, A. C., Turriff, A., Muskett, J. A., Zalewski, C. K., King, K. A., Ahmed, Z. M., Riazuddin, S., Ahmad, N., Hussain, Z., Qasim, M., and 12 others.
|
|
<strong>Allelic hierarchy of CDH23 mutations causing non-syndromic deafness DFNB12 or Usher syndrome USH1D in compound heterozygotes.</strong>
|
|
J. Med. Genet. 48: 767-775, 2011.
|
|
|
|
|
|
[PubMed: 21940737]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmedgenet-2011-100262]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schultz, J. M., Yang, Y., Caride, A. J., Filoteo, A. G., Penheiter, A. R., Lagziel, A., Morell, R. J., Mohiddin, S. A., Fananapazir, L., Madeo, A. C., Penniston, J. T., Griffith, A. J.
|
|
<strong>Modification of human hearing loss by plasma-membrane calcium pump PMCA2.</strong>
|
|
New Eng. J. Med. 352: 1557-1564, 2005. Note: Erratum: New Eng. J. Med. 352: 2362 only, 2005.
|
|
|
|
|
|
[PubMed: 15829536]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa043899]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schwander, M., Xiong, W., Tokita, J., Lelli, A., Elledge, H. M., Kazmierczak, P., Sczaniecka, A., Kolatkar, A., Wiltshire, T., Kuhn, P., Holt, J. R., Kachar, B., Tarantino, L., Muller, U.
|
|
<strong>A mouse model for nonsyndromic deafness (DFNB12) links hearing loss to defects in tip links of mechanosensory hair cells.</strong>
|
|
Proc. Nat. Acad. Sci. 106: 5252-5257, 2009.
|
|
|
|
|
|
[PubMed: 19270079]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0900691106]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Siemens, J., Kazmierczak, P., Reynolds, A., Sticker, M., Littlewood-Evans, A., Muller, U.
|
|
<strong>The Usher syndrome proteins cadherin 23 and harmonin form a complex by means of PDZ-domain interactions.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 14946-14951, 2002.
|
|
|
|
|
|
[PubMed: 12407180]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.232579599]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sotomayor, M., Weihofen, W. A., Gaudet, R., Corey, D. P.
|
|
<strong>Structural determinants of cadherin-23 function in hearing and deafness.</strong>
|
|
Neuron 66: 85-100, 2010.
|
|
|
|
|
|
[PubMed: 20399731]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.neuron.2010.03.028]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sotomayor, M., Weihofen, W. A., Gaudet, R., Corey, D. P.
|
|
<strong>Structure of a force-conveying cadherin bond essential for inner-ear mechanotransduction.</strong>
|
|
Nature 492: 128-132, 2012.
|
|
|
|
|
|
[PubMed: 23135401]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature11590]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
von Brederlow, B., Bolz, H., Janecke, A., La O Cabrera, A., Rudolph, G., Lorenz, B., Schwinger, E., Gal, A.
|
|
<strong>Identification and in vitro expression of novel CDH23 mutations of patients with Usher syndrome type 1D.</strong>
|
|
Hum. Mutat. 19: 268-273, 2002.
|
|
|
|
|
|
[PubMed: 11857743]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.10049]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wagatsuma, M., Kitoh, R., Suzuki, H., Fukuoka, H., Takumi, Y., Usami, S.
|
|
<strong>Distribution and frequencies of CDH23 mutations in Japanese patients with non-syndromic hearing loss.</strong>
|
|
Clin. Genet. 72: 339-344, 2007.
|
|
|
|
|
|
[PubMed: 17850630]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2007.00833.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, Q., Peng, C., Song, J., Zhang, Y., Chen, J., Song, Z., Shou, X., Ma, Z., Peng, H., Jian, X., He, W., Ye, Z., and 22 others.
|
|
<strong>Germline mutations in CDH23, encoding cadherin-related 23, are associated with both familial and sporadic pituitary adenomas.</strong>
|
|
Am. J. Hum. Genet. 100: 817-823, 2017.
|
|
|
|
|
|
[PubMed: 28413019]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2017.03.011]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zheng, Q. Y., Yan, D., Ouyang, X. M., Du, L. L., Yu, H., Chang, B., Johnson, K. R., Liu, X. Z.
|
|
<strong>Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.</strong>
|
|
Hum. Molec. Genet. 14: 103-111, 2005.
|
|
|
|
|
|
[PubMed: 15537665]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi010]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 06/21/2017<br>Ada Hamosh - updated : 1/7/2013<br>Patricia A. Hartz - updated : 4/26/2012<br>Cassandra L. Kniffin - updated : 3/19/2012<br>Patricia A. Hartz - updated : 7/26/2011<br>Cassandra L. Kniffin - updated : 8/7/2009<br>Cassandra L. Kniffin - updated : 1/8/2008<br>George E. Tiller - updated : 10/31/2007<br>Ada Hamosh - updated : 10/16/2007<br>George E. Tiller - updated : 4/5/2007<br>Victor A. McKusick - updated : 10/26/2006<br>Victor A. McKusick - updated : 4/21/2005<br>Victor A. McKusick - updated : 8/21/2003<br>Patricia A. Hartz - updated : 3/10/2003<br>Victor A. McKusick - updated : 1/23/2003<br>Victor A. McKusick - updated : 12/10/2002<br>Victor A. McKusick - updated : 8/16/2002<br>Victor A. McKusick - updated : 4/4/2002<br>Victor A. McKusick - updated : 1/23/2001
|
|
</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 : 1/2/2001
|
|
</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 : 09/27/2017<br>carol : 09/26/2017<br>carol : 09/01/2017<br>carol : 09/01/2017<br>ckniffin : 06/21/2017<br>carol : 10/04/2016<br>carol : 07/16/2015<br>mcolton : 7/2/2015<br>carol : 8/16/2013<br>terry : 4/4/2013<br>alopez : 1/7/2013<br>terry : 1/7/2013<br>mgross : 5/2/2012<br>mgross : 5/2/2012<br>mgross : 5/2/2012<br>terry : 4/26/2012<br>alopez : 3/22/2012<br>terry : 3/19/2012<br>ckniffin : 3/19/2012<br>carol : 2/29/2012<br>mgross : 8/8/2011<br>terry : 7/26/2011<br>carol : 5/5/2011<br>alopez : 4/6/2011<br>wwang : 12/3/2010<br>wwang : 8/28/2009<br>ckniffin : 8/7/2009<br>alopez : 3/18/2008<br>alopez : 3/18/2008<br>wwang : 1/28/2008<br>ckniffin : 1/8/2008<br>alopez : 11/6/2007<br>terry : 10/31/2007<br>alopez : 10/18/2007<br>alopez : 10/18/2007<br>terry : 10/16/2007<br>alopez : 4/17/2007<br>terry : 4/5/2007<br>alopez : 10/27/2006<br>terry : 10/26/2006<br>tkritzer : 4/28/2005<br>terry : 4/21/2005<br>alopez : 9/2/2003<br>alopez : 8/22/2003<br>terry : 8/21/2003<br>tkritzer : 5/7/2003<br>mgross : 3/13/2003<br>mgross : 3/13/2003<br>terry : 3/10/2003<br>carol : 3/10/2003<br>tkritzer : 1/27/2003<br>terry : 1/23/2003<br>carol : 12/10/2002<br>tkritzer : 12/6/2002<br>terry : 12/4/2002<br>tkritzer : 8/23/2002<br>tkritzer : 8/21/2002<br>terry : 8/16/2002<br>cwells : 4/15/2002<br>cwells : 4/9/2002<br>terry : 4/4/2002<br>carol : 12/7/2001<br>carol : 3/30/2001<br>carol : 1/23/2001<br>carol : 1/23/2001<br>terry : 1/23/2001<br>mgross : 1/3/2001<br>mgross : 1/2/2001
|
|
</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>
|
|
|
|
|