7083 lines
636 KiB
Text
7083 lines
636 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
|
|
|
|
- *606201 - WOLFRAMIN ER TRANSMEMBRANE GLYCOPROTEIN; WFS1
|
|
|
|
|
|
- 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=606201"><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">*606201</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/606201">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=ENSG00000109501;t=ENST00000226760" 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=7466" 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=606201" 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=ENSG00000109501;t=ENST00000226760" 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_001145853,NM_006005" 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_006005" 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=606201" 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=05864&isoform_id=05864_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/WFS1" 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/3766441,3777583,20987221,119602802,119602803,119602804,189053571,194381614,224994203,224994205,317373289,546570545,803432213,957950387,957950390,2037729249,2037729251,2037729253,2037729255,2037729257" 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/O76024" 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=7466" 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=ENSG00000109501;t=ENST00000226760" 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=WFS1" 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=WFS1" 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+7466" 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/WFS1" 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:7466" 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/7466" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr4&hgg_gene=ENST00000226760.5&hgg_start=6269850&hgg_end=6303265&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:12762" 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:12762" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=606201[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=606201[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/WFS1/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/ENSG00000109501" 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=WFS1" 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=WFS1" 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=WFS1" 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://webh01.ua.ac.be/hhh/" 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/WFS1" 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 style="margin-left: 0.5em;"><a href="http://www.euro-wabb.org/en/lovd-genetic-variation-database" title="EURO-WABB Project Open Variation Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">EURO-WABB Project Open Var…</a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=WFS1&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/PA37365" 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:12762" 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/FBgn0039003.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:1328355" 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/WFS1#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:1328355" 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/7466/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=7466" 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-050809-19" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:7466" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://reactome.org/content/query?q=WFS1&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>
|
|
606201
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
WOLFRAMIN ER TRANSMEMBRANE GLYCOPROTEIN; WFS1
|
|
|
|
</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">
|
|
WOLFRAMIN
|
|
</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=WFS1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">WFS1</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/4/69?start=-3&limit=10&highlight=69">4p16.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr4:6269850-6303265&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">4:6,269,850-6,303,265</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=116400,125853,600965,222300,614296" 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="5">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/4/69?start=-3&limit=10&highlight=69">
|
|
4p16.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Cataract 41
|
|
|
|
<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
|
<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
|
</span>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/116400"> 116400 </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">
|
|
{Diabetes mellitus, noninsulin-dependent, association with}
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/125853"> 125853 </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 dominant 6/14/38
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/600965"> 600965 </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">
|
|
Wolfram syndrome 1
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/222300"> 222300 </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">
|
|
Wolfram-like syndrome, autosomal dominant
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/614296"> 614296 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/606201" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/606201" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#28" class="mim-tip-reference" title="Strom, T. M., Hortnagel, K., Hofmann, S., Gekeler, F., Scharfe, C., Rabl, W., Gerbitz, K. D., Meitinger, T. <strong>Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein.</strong> Hum. Molec. Genet. 7: 2021-2028, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9817917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9817917</a>] [<a href="https://doi.org/10.1093/hmg/7.13.2021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9817917">Strom et al. (1998)</a> screened 4 candidate genes in a refined critical linkage interval for Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>) on chromosome 4p16. One of these genes, WFS1, which they called 'wolframin,' codes for a predicted 890-amino acid transmembrane protein with a calculated molecular mass of about 100 kD. WFS1 was predicted to have 9 central transmembrane domains, with an extracytoplasmic N terminus and an intracytoplasmic C terminus. Human WFS1 shares 87% amino acid identity with its mouse homolog. Northern blot analysis detected a 3.6-kb transcript in all human tissues examined. Expression was strong in heart, intermediate in brain, placenta, lung, and pancreas, and weak in liver, skeletal muscle, and kidney. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9817917" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Independently, <a href="#18" class="mim-tip-reference" title="Inoue, H., Tanizawa, Y., Wasson, J., Behn, P., Kalidas, K., Bernal-Mizrachi, E., Meuckler, M., Marshall, H., Donis-Keller, H., Crock, P., Rogers, D., Mikuni, M., Kumashiro, H., Higashi, K., Sobue, G., Oka, Y., Permutt, M. A. <strong>A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).</strong> Nature Genet. 20: 143-148, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771706</a>] [<a href="https://doi.org/10.1038/2441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9771706">Inoue et al. (1998)</a> positionally cloned the WFS1 gene. They obtained the full-length cDNA by screening an infant brain cDNA library, followed by 5-prime RACE. The WFS1 hydrophobicity curve suggested the presence of approximately 10 transmembrane segments in WFS1. Northern blot analysis detected a major transcript of 3.7 kb in all human tissues examined, including pancreas. Northern blot analysis of total RNA showed high expression of WFS1 in pancreatic islets compared with exocrine pancreas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9771706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#16" class="mim-tip-reference" title="Hofmann, S., Philbrook, C., Gerbitz, K.-D., Bauer, M. F. <strong>Wolfram syndrome: structural and functional analyses of mutant and wild-type wolframin, the WFS1 gene product.</strong> Hum. Molec. Genet. 12: 2003-2012, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12913071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12913071</a>] [<a href="https://doi.org/10.1093/hmg/ddg214" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12913071">Hofmann et al. (2003)</a> reported that wolframin is ubiquitously expressed, with highest levels in brain, pancreas, heart, and insulinoma beta-cell lines. Wolframin assembled into higher molecular weight complexes of 400 kD in the membrane, and N-glycosylation was essential for its biogenesis and stability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12913071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By Western blot, <a href="#1" class="mim-tip-reference" title="Berry, V., Gregory-Evans, C., Emmett, W., Waseem, N., Raby, J., Prescott, D., Moore, A. T., Bhattacharya, S. S. <strong>Wolfram gene (WFS1) mutation causes autosomal dominant congenital nuclear cataract in humans.</strong> Europ. J. Hum. Genet. 21: 1356-1360, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23531866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23531866</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23531866[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2013.52" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23531866">Berry et al. (2013)</a> demonstrated expression of Wfs1 in whole mouse eye at embryonic day 18.5 (E18.5) and in whole lens tissue extract at postnatal days 3 and 21. Immunocytochemistry demonstrated high-level expression of Wfs1 in the developing mouse lens at E18.5, but not at E12.5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23531866" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneStructure" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneStructureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneStructureFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#18" class="mim-tip-reference" title="Inoue, H., Tanizawa, Y., Wasson, J., Behn, P., Kalidas, K., Bernal-Mizrachi, E., Meuckler, M., Marshall, H., Donis-Keller, H., Crock, P., Rogers, D., Mikuni, M., Kumashiro, H., Higashi, K., Sobue, G., Oka, Y., Permutt, M. A. <strong>A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).</strong> Nature Genet. 20: 143-148, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771706</a>] [<a href="https://doi.org/10.1038/2441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9771706">Inoue et al. (1998)</a> found that the WFS1 gene contains 8 exons, spanning 33.4 kb of genomic DNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9771706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>By genomic sequence analysis, <a href="#28" class="mim-tip-reference" title="Strom, T. M., Hortnagel, K., Hofmann, S., Gekeler, F., Scharfe, C., Rabl, W., Gerbitz, K. D., Meitinger, T. <strong>Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein.</strong> Hum. Molec. Genet. 7: 2021-2028, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9817917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9817917</a>] [<a href="https://doi.org/10.1093/hmg/7.13.2021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9817917">Strom et al. (1998)</a> mapped the WFS1 gene to chromosome 4p16. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9817917" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Using biochemical methods, <a href="#29" class="mim-tip-reference" title="Takeda, K., Inoue, K., Tanizawa, Y., Matsuzaki, Y., Oba, J., Watanabe Y., Shinoda, K., Oka, Y. <strong>WFS1 (Wolfram syndrome 1) gene product: predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain.</strong> Hum. Molec. Genet. 10: 477-484, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11181571/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11181571</a>] [<a href="https://doi.org/10.1093/hmg/10.5.477" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11181571">Takeda et al. (2001)</a> showed that the WFS1 protein is an integral, endoglycosidase H-sensitive membrane glycoprotein that localizes primarily in the endoplasmic reticulum (ER). Immunofluorescence staining of overexpressed WFS1 in transiently transfected COS-7 cells showed a characteristic reticular pattern over the cytoplasm and overlapped with ER marker staining. In rat brain, at both the protein and mRNA level, WFS1 was present predominantly in selected neurons in the hippocampus CA1, amygdaloid areas, olfactory tubercle, and superficial layer of the allocortex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11181571" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Osman, A. A., Saito, M., Makepeace, C., Permutt, M. A., Schlesinger, P., Mueckler, M. <strong>Wolframin expression induces novel ion channel activity in endoplasmic reticulum membranes and increases intracellular calcium.</strong> J. Biol. Chem. 278: 52755-52762, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14527944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14527944</a>] [<a href="https://doi.org/10.1074/jbc.M310331200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14527944">Osman et al. (2003)</a> found that human WFS1 expressed in Xenopus oocytes localized to the ER. Planar oocyte lipid bilayers containing WFS1 showed a large cation-selective channel activity that was blocked by Mg(2+) or Ca(2+). Fused bilayers containing WFS1 showed an elevated slope conductance following activation by inositol 1,4,5-triphosphate. <a href="#23" class="mim-tip-reference" title="Osman, A. A., Saito, M., Makepeace, C., Permutt, M. A., Schlesinger, P., Mueckler, M. <strong>Wolframin expression induces novel ion channel activity in endoplasmic reticulum membranes and increases intracellular calcium.</strong> J. Biol. Chem. 278: 52755-52762, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14527944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14527944</a>] [<a href="https://doi.org/10.1074/jbc.M310331200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14527944">Osman et al. (2003)</a> proposed that WFS1 functions as an ER calcium channel or as a regulator of ER calcium channel activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14527944" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 real-time PCR, <a href="#9" class="mim-tip-reference" title="Fonseca, S. G., Fukuma, M., Lipson, K. L., Nguyen, L. X., Allen, J. R., Oka, Y., Urano, F. <strong>WFS1 is a novel component of the unfolded protein response and maintains homeostasis of the endoplasmic reticulum in pancreatic beta-cells.</strong> J. Biol. Chem. 280: 39609-39615, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16195229/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16195229</a>] [<a href="https://doi.org/10.1074/jbc.M507426200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16195229">Fonseca et al. (2005)</a> found that Wfs1 was induced by ER stress in mouse fibroblasts and that its expression was controlled by Ire1-alpha (ERN1; <a href="/entry/604033">604033</a>) and Perk (EIF2AK3; <a href="/entry/604032">604032</a>), which are involved in the unfolded protein response. Expression of Wfs1 was upregulated in mouse islets during glucose-induced insulin secretion, and knockdown of Wfs1 in mouse beta cells resulted in ER stress and cell dysfunction. <a href="#9" class="mim-tip-reference" title="Fonseca, S. G., Fukuma, M., Lipson, K. L., Nguyen, L. X., Allen, J. R., Oka, Y., Urano, F. <strong>WFS1 is a novel component of the unfolded protein response and maintains homeostasis of the endoplasmic reticulum in pancreatic beta-cells.</strong> J. Biol. Chem. 280: 39609-39615, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16195229/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16195229</a>] [<a href="https://doi.org/10.1074/jbc.M507426200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16195229">Fonseca et al. (2005)</a> hypothesized that Wolfram syndrome involves chronic ER stress in pancreatic beta cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16195229" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 yeast 2-hybrid analysis, <a href="#34" class="mim-tip-reference" title="Zatyka, M., Ricketts, C., Xavier, G. S., Minton, J., Fenton, S., Hofmann-Thiel, S., Rutter, G. A., Barrett, T. G. <strong>Sodium-potassium ATPase beta-1 subunit is a molecular partner of Wolframin, an endoplasmic reticulum protein involved in ER stress.</strong> Hum. Molec. Genet. 17: 190-200, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17947299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17947299</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17947299[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/ddm296" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17947299">Zatyka et al. (2008)</a> found that the C-terminal domain of WFS1, which is positioned in the ER lumen, bound the C-terminal domain of the ER-localized Na+/K+ ATPase beta-1 subunit (ATP1B1; <a href="/entry/182330">182330</a>). The interaction was confirmed by reciprocal coimmunoprecipitation analysis of proteins expressed in transfected COS-7 cells and endogenous proteins in human and mouse cell lines. Wolfram syndrome patient fibroblasts with 2 different WFS1 mutations showed reduced ATP1B1 levels. Conversely, knockdown of Atp1b1 expression in a mouse insulinoma cell line led to reduced Wfs1 expression. <a href="#34" class="mim-tip-reference" title="Zatyka, M., Ricketts, C., Xavier, G. S., Minton, J., Fenton, S., Hofmann-Thiel, S., Rutter, G. A., Barrett, T. G. <strong>Sodium-potassium ATPase beta-1 subunit is a molecular partner of Wolframin, an endoplasmic reticulum protein involved in ER stress.</strong> Hum. Molec. Genet. 17: 190-200, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17947299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17947299</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17947299[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/ddm296" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17947299">Zatyka et al. (2008)</a> concluded that interaction with WFS1 may be important for ATP1B1 maturation in the ER and that loss of this interaction may contribute to the pathology seen in Wolfram syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17947299" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Wolfram Syndrome 1</em></strong></p><p>
|
|
<a href="#28" class="mim-tip-reference" title="Strom, T. M., Hortnagel, K., Hofmann, S., Gekeler, F., Scharfe, C., Rabl, W., Gerbitz, K. D., Meitinger, T. <strong>Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein.</strong> Hum. Molec. Genet. 7: 2021-2028, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9817917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9817917</a>] [<a href="https://doi.org/10.1093/hmg/7.13.2021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9817917">Strom et al. (1998)</a> identified loss-of-function mutations in both alleles of the WFS1 gene in patients with Wolfram syndrome-1 (WFS1; <a href="/entry/222300">222300</a>). Homozygous mutations were found in 5 families; compound heterozygosity was found in 3 other families. In a ninth family, only a heterozygous stop mutation was found. No mutations in either allele were detected in 3 other families. One of the families was reportedly consanguineous but no mutations were detected in that family. Mutations in exon 1, which was not included in the mutation screen, intronic mutations including deletions, or mutations in the regulatory flanking regions of the gene could be pathogenic in these families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9817917" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Hardy, C., Khanim, F., Torres, R., Scott-Brown, M., Seller, A., Poulton, J., Collier, D., Kirk, J., Polymeropoulos, M., Latif, F., Barrett, T. <strong>Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1.</strong> Am. J. Hum. Genet. 65: 1279-1290, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10521293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10521293</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10521293[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/10.1086/302609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10521293">Hardy et al. (1999)</a> performed direct DNA sequencing to screen the entire coding region of the WFS1 gene in 30 patients from 19 British kindreds with Wolfram syndrome. DNA was also screened for structural rearrangements (deletions and duplications) and point mutations in mtDNA. No pathogenic mtDNA mutations were found in this cohort. The authors identified 24 mutations in the WFS1 gene: 8 nonsense mutations, 8 missense mutations, 3 in-frame deletions, 1 in-frame insertion, and 4 frameshift mutations. Of these, 23 were novel mutations, and most occurred in exon 8. Most patients were compound heterozygotes for 2 mutations, and there was no common founder mutation. The data were also analyzed for genotype-phenotype relationships. Although some interesting cases were noted, consideration of the small sample size and frequency of each mutation indicated no clear-cut correlations between any of the observed mutations and disease severity. There were no obvious mutation hotspots or clusters. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10521293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Khanim, F., Kirk, J., Latif, F., Barrett, T. G. <strong>WFS1/Wolframin mutations, Wolfram syndrome, and associated diseases.</strong> Hum. Mutat. 17: 357-367, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11317350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11317350</a>] [<a href="https://doi.org/10.1002/humu.1110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11317350">Khanim et al. (2001)</a> stated that mutation analysis of the WFS1 gene had identified mutations in 90% of patients with Wolfram syndrome. Most were compound heterozygotes with private mutations distributed throughout the gene with no obvious hotspots. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11317350" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Colosimo, A., Guida, V., Rigoli, L., Di Bella, C., De Luca, A., Briuglia, S., Stuppia, L., Salpietro, D. C., Dallapiccolo, B. <strong>Molecular detection of novel WFS1 mutations in patients with Wolfram syndrome by a DHPLC-based assay.</strong> Hum. Mutat. 21: 622-629, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12754709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12754709</a>] [<a href="https://doi.org/10.1002/humu.10215" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12754709">Colosimo et al. (2003)</a> identified 19 different mutations in the WFS1 gene in a study of 19 Italian patients with Wolfram syndrome. Mutations were found in 18 of the 19 patients (95%). All of the mutations except 1 were novel, were preferentially located in WFS1 exon 8, and included deletions, insertions, duplications, and nonsense and missense changes. In particular, a 16-bp deletion in WFS1 codon 454 (<a href="#0019">606201.0019</a>) was detected in 5 different unrelated nuclear families, being the most prevalent alteration in these Italian patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12754709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a review of the mutational spectrum of the WFS1 gene, <a href="#5" class="mim-tip-reference" title="Cryns, K., Sivakumaran, T. A., Van den Ouweland, J. M. W., Pennings, R. J. E., Cremers, C. W. R. J., Flothmann, K., Young, T.-L., Smith, R. J. H., Lesperance, M. M., Van Camp, G. <strong>Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease.</strong> Hum. Mutat. 22: 275-287, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12955714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12955714</a>] [<a href="https://doi.org/10.1002/humu.10258" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12955714">Cryns et al. (2003)</a> pointed out that mutations associated with Wolfram syndrome are spread over the entire coding region and are typically inactivating, suggesting that a loss of function causes the disease phenotype. In contrast, only noninactivating mutations have been found in DFNA6/14 families, and these mutations are mainly located in the C-terminal protein domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12955714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of 6 Spanish families with a total of 7 Wolfram syndrome patients, <a href="#7" class="mim-tip-reference" title="Domenech, E., Gomez-Zaera, M., Nunes, V. <strong>Study of the WFS1 gene and mitochondrial DNA in Spanish Wolfram syndrome families.</strong> Clin. Genet. 65: 463-469, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15151504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15151504</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2004.00249.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15151504">Domenech et al. (2004)</a> identified 3 previously undescribed mutations in the WFS1 gene as well as the duplication 409dup16 (<a href="#0013">606201.0013</a>), previously reported as 425ins16 (<a href="#11" class="mim-tip-reference" title="Gomez-Zaera, M., Strom, T. M., Rodriguez, B., Estivill, X., Meitinger, T., Nunes, V. <strong>Presence of a major WFS1 mutation in Spanish Wolfram syndrome pedigrees.</strong> Molec. Genet. Metab. 72: 72-81, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11161832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11161832</a>] [<a href="https://doi.org/10.1006/mgme.2000.3107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11161832">Gomez-Zaera et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15151504+11161832" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Hansen, L., Eiberg, H., Barrett, T., Bek, T., Kjaersgaard, P., Tranebjaerg, L., Rosenberg, T. <strong>Mutation analysis of the WFS1 gene in seven Danish Wolfram syndrome families; four new mutations identified.</strong> Europ. J. Hum. Genet. 13: 1275-1284, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16151413/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16151413</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201491" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16151413">Hansen et al. (2005)</a> identified mutations in the WFS1 gene in 8 affected members of 7 Danish families with Wolfram syndrome. Four of the mutations were novel. Mutations were identified in 11 of 14 disease chromosomes; in 3 families, only 1 mutation was found. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16151413" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#33" class="mim-tip-reference" title="Zalloua, P. A., Azar, S. T., Delepine, M., Makhoul, N. J., Blanc, H., Sanyoura, M., Lavergne, A., Stankov, K., Lemainque, A., Baz, P., Julier, C. <strong>WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon.</strong> Hum. Molec. Genet. 17: 4012-4021, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18806274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18806274</a>] [<a href="https://doi.org/10.1093/hmg/ddn304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18806274">Zalloua et al. (2008)</a> performed family-based linkage analysis followed by systematic screening of WFS1 exons in Lebanese juvenile-onset insulin-dependent diabetes (<a href="/entry/222100">222100</a>) probands and found homozygous or compound heterozygous WFS1 mutations in 22 (5.5%) of the 399 probands, of whom 17 were diagnosed with WFS and 5 with nonsyndromic nonautoimmune diabetes mellitus. Overall, 38 probands and affected family members were homozygous or compound heterozygous for WFS1 mutations, 11 (29%) of whom were diagnosed with nonsyndromic DM; all of the latter patients carried a complex WFS1 mutation (<a href="#0024">606201.0024</a>), which the authors designated WFS1(LIB) and which resulted in the delayed onset or absence of extrapancreatic features of WFS. In addition, there were 2 patients with an initial diagnosis of nonsyndromic DM that was revised to WFS when they developed optic atrophy during the course of the study; <a href="#33" class="mim-tip-reference" title="Zalloua, P. A., Azar, S. T., Delepine, M., Makhoul, N. J., Blanc, H., Sanyoura, M., Lavergne, A., Stankov, K., Lemainque, A., Baz, P., Julier, C. <strong>WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon.</strong> Hum. Molec. Genet. 17: 4012-4021, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18806274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18806274</a>] [<a href="https://doi.org/10.1093/hmg/ddn304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18806274">Zalloua et al. (2008)</a> noted that longer follow-up of the WFS1-mutated nonsyndromic DM patients or a specific study of adult patient populations would be needed to determine whether a subset of the WFS1(LIB) patients are exempted from extrapancreatic manifestations during their lifetime. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18806274" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Pathophysiology of WFS1 Mutations in Wolfram Syndrome</em></strong></p><p>
|
|
In a patient carrying both a nonsense (frameshift) and a missense mutation, <a href="#16" class="mim-tip-reference" title="Hofmann, S., Philbrook, C., Gerbitz, K.-D., Bauer, M. F. <strong>Wolfram syndrome: structural and functional analyses of mutant and wild-type wolframin, the WFS1 gene product.</strong> Hum. Molec. Genet. 12: 2003-2012, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12913071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12913071</a>] [<a href="https://doi.org/10.1093/hmg/ddg214" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12913071">Hofmann et al. (2003)</a> detected mRNA levels half that of controls; sequencing confirmed that these transcripts were exclusively derived from the missense allele. Transfection experiments with the missense transcript revealed a markedly reduced steady-state level of wolframin and a strongly reduced half-life. <a href="#16" class="mim-tip-reference" title="Hofmann, S., Philbrook, C., Gerbitz, K.-D., Bauer, M. F. <strong>Wolfram syndrome: structural and functional analyses of mutant and wild-type wolframin, the WFS1 gene product.</strong> Hum. Molec. Genet. 12: 2003-2012, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12913071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12913071</a>] [<a href="https://doi.org/10.1093/hmg/ddg214" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12913071">Hofmann et al. (2003)</a> concluded that the pathophysiology in Wolfram syndrome in the presence of a missense mutation is likely that of reduced protein dosage rather than dysfunction of the mutant protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12913071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By analyzing WFS1 patient cells and COS-7 cells expressing 4 missense and 2 truncating mutations in WFS1, <a href="#15" class="mim-tip-reference" title="Hofmann, S., Bauer, M. F. <strong>Wolfram syndrome-associated mutations lead to instability and proteasomal degradation of wolframin.</strong> FEBS Lett. 580: 4000-4004, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16806192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16806192</a>] [<a href="https://doi.org/10.1016/j.febslet.2006.06.036" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16806192">Hofmann and Bauer (2006)</a> found that all mutations led to drastically reduced steady-state levels of WFS1 protein. Mutant proteins were highly unstable and were removed by proteasomal degradation. <a href="#15" class="mim-tip-reference" title="Hofmann, S., Bauer, M. F. <strong>Wolfram syndrome-associated mutations lead to instability and proteasomal degradation of wolframin.</strong> FEBS Lett. 580: 4000-4004, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16806192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16806192</a>] [<a href="https://doi.org/10.1016/j.febslet.2006.06.036" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16806192">Hofmann and Bauer (2006)</a> concluded that WFS1 mutations cause loss of function by cellular depletion of WFS1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16806192" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 Dominant Nonsyndromic Sensorineural Deafness</em></strong></p><p>
|
|
<a href="#2" class="mim-tip-reference" title="Bespalova, I. N., Van Camp, G., Bom, S. J. H., Brown, D. J., Cryns, K., DeWan, A. T., Erson, A. E., Flothmann, K., Kunst, H. P. M., Kurnool, P., Sivakumaran, T. A., Cremers, C. W. R. J., Leal, S. M., Burmeister, M., Lesperance, M. M. <strong>Mutations in the Wolfram syndrome 1 gene (WFS1) are a common cause of low frequency sensorineural hearing loss.</strong> Hum. Molec. Genet. 10: 2501-2508, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709537</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11709537[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/10.22.2501" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11709537">Bespalova et al. (2001)</a> defined a subset of nonsyndromic sensorineural hearing loss affecting low frequencies without profound deafness (<a href="/entry/600965">600965</a>) in which all individuals studied had WFS1 mutations (e.g., <a href="#0015">606201.0015</a>). This subset included families that had been linked to loci designated DFNA6 and DFNA14. <a href="#2" class="mim-tip-reference" title="Bespalova, I. N., Van Camp, G., Bom, S. J. H., Brown, D. J., Cryns, K., DeWan, A. T., Erson, A. E., Flothmann, K., Kunst, H. P. M., Kurnool, P., Sivakumaran, T. A., Cremers, C. W. R. J., Leal, S. M., Burmeister, M., Lesperance, M. M. <strong>Mutations in the Wolfram syndrome 1 gene (WFS1) are a common cause of low frequency sensorineural hearing loss.</strong> Hum. Molec. Genet. 10: 2501-2508, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709537</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11709537[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/10.22.2501" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11709537">Bespalova et al. (2001)</a> concluded that mutations in the WFS1 gene are a common cause of sensorineural hearing loss. Additionally, an autosomal dominant sensorineural hearing loss designated DFNA38 was shown to be caused by mutation in the WFS1 gene (<a href="#0014">606201.0014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709537" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Cryns, K., Pfister, M., Pennings, R. J. E., Bom, S. J. H., Flothmann, K., Caethoven, G., Kremer, H., Schatteman, I., Koln, K. A., Toth, T., Kupka, S., Blin, N., Nurnberg, P., Thiele, H., van de Heyning, P. H., Reardon, W., Stephens, D., Cremers, C. W. R. J., Smith, R. J. H., Van Camp, G. <strong>Mutations in the WFS1 gene that cause low-frequency sensorineural hearing loss are small non-inactivating mutations.</strong> Hum. Genet. 110: 389-394, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12073007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12073007</a>] [<a href="https://doi.org/10.1007/s00439-002-0719-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12073007">Cryns et al. (2002)</a> stated that only 2 of the more than 70 loci identified as associated with hereditary hearing impairment are associated with an auditory phenotype that predominantly affects the low frequencies: DFNA1 (<a href="/entry/124900">124900</a>) and DFNA6/14 (<a href="/entry/600965">600965</a>). <a href="#4" class="mim-tip-reference" title="Cryns, K., Pfister, M., Pennings, R. J. E., Bom, S. J. H., Flothmann, K., Caethoven, G., Kremer, H., Schatteman, I., Koln, K. A., Toth, T., Kupka, S., Blin, N., Nurnberg, P., Thiele, H., van de Heyning, P. H., Reardon, W., Stephens, D., Cremers, C. W. R. J., Smith, R. J. H., Van Camp, G. <strong>Mutations in the WFS1 gene that cause low-frequency sensorineural hearing loss are small non-inactivating mutations.</strong> Hum. Genet. 110: 389-394, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12073007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12073007</a>] [<a href="https://doi.org/10.1007/s00439-002-0719-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12073007">Cryns et al. (2002)</a> did mutation screening of the WFS1 gene in 8 autosomal dominant families and 12 sporadic cases in which affected persons had low-frequency sensorineural hearing impairment. They identified 7 missense mutations and a single amino acid deletion affecting conserved amino acids in 6 families and 1 sporadic case, indicating that mutations in WFS1 are a major cause of inherited low-frequency hearing impairment. Among the 10 WFS1 mutations reported in low-frequency sensorineural hearing impairment, none was expected to lead to premature protein termination, and 9 clustered in the C-terminal protein domain. In contrast, 64% of the Wolfram syndrome mutations are inactivating. The results indicated that only noninactivating mutations in WFS1 are responsible for nonsyndromic low-frequency hearing impairment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12073007" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Fukuoka, H., Kanda, Y., Ohta, S., Usami, S. <strong>Mutations in the WFS1 gene are a frequent cause of autosomal dominant nonsyndromic low-frequency hearing loss in Japanese.</strong> J. Hum. Genet. 52: 510-515, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17492394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17492394</a>] [<a href="https://doi.org/10.1007/s10038-007-0144-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17492394">Fukuoka et al. (2007)</a> analyzed the WFS1 gene in 206 Japanese autosomal dominant and 64 autosomal recessive (sporadic) nonsyndromic hearing loss probands with varying severities of hearing loss and identified 2 different missense mutations in 3 unrelated families (see <a href="#0014">606201.0014</a> and <a href="#0020">606201.0020</a>, respectively). All of the mutation-positive patients had dominantly inherited low-frequency sensorineural hearing loss. Because both mutations had previously been identified in patients of European ancestry, <a href="#10" class="mim-tip-reference" title="Fukuoka, H., Kanda, Y., Ohta, S., Usami, S. <strong>Mutations in the WFS1 gene are a frequent cause of autosomal dominant nonsyndromic low-frequency hearing loss in Japanese.</strong> J. Hum. Genet. 52: 510-515, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17492394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17492394</a>] [<a href="https://doi.org/10.1007/s10038-007-0144-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17492394">Fukuoka et al. (2007)</a> suggested that the sites are likely to be mutation hotspots. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17492394" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 Dominant Wolfram-like Syndrome</em></strong></p><p>
|
|
<a href="#6" class="mim-tip-reference" title="Domenech, E., Gomez-Zaera, M., Nunes, V. <strong>WFS1 mutations in Spanish patients with diabetes mellitus and deafness.</strong> Europ. J. Hum. Genet. 10: 421-426, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12107816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12107816</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200823" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12107816">Domenech et al. (2002)</a> screened the WFS1 gene in 48 patients with autosomal recessive deafness, 38 patients with type 2 diabetes mellitus (T2D; <a href="/entry/125853">125853</a>), and 23 patients with both deafness and T2D. In 3 unrelated patients who had both deafness and diabetes, they identified 3 different heterozygous missense mutations, which were located in the intracytoplasmic domain of the protein and were not detected in 49 healthy controls. <a href="#6" class="mim-tip-reference" title="Domenech, E., Gomez-Zaera, M., Nunes, V. <strong>WFS1 mutations in Spanish patients with diabetes mellitus and deafness.</strong> Europ. J. Hum. Genet. 10: 421-426, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12107816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12107816</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200823" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12107816">Domenech et al. (2002)</a> stated that the lack of knowledge about the function of WFS1 made it difficult to explain the possible contribution of these mutations to the diseases. One of the mutations, V871M, was also found in a patient who had only deafness and was present in her deaf sister, but was detected in her unaffected father. (The V871M variant had previously been detected by <a href="#32" class="mim-tip-reference" title="Young, T.-L., Ives, E., Lynch, E., Person, R., Snook, S., MacLaren, L., Cater, T., Griffin, A., Fernandez, B., Lee, M. K., King, M.-C. <strong>Non-syndromic progressive hearing loss DFNA38 is caused by heterozygous missense mutation in the Wolfram syndrome gene WFS1.</strong> Hum. Molec. Genet. 10: 2509-2514, 2001. Note: Erratum: Hum. Molec. Genet. 10: 3111 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709538</a>] [<a href="https://doi.org/10.1093/hmg/10.22.2509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11709538">Young et al., 2001</a> in a family with autosomal dominant deafness, but did not segregate with disease in that family; see <a href="#0014">606201.0014</a>.) <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11709538+12107816" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 3-generation Danish family segregating an autosomal dominant Wolfram-like syndrome (WFSL; <a href="/entry/614296">614296</a>) in which affected individuals had deafness, optic atrophy, and impaired glucose regulation mapping to chromosome 4p16.3, <a href="#8" class="mim-tip-reference" title="Eiberg, H., Hansen, L., Kjer, B., Hansen, T., Pedersen, O., Bille, M., Rosenberg, T., Tranebjaerg, L. <strong>Autosomal dominant optic atrophy associated with hearing impairment and impaired glucose regulation caused by a missense mutation in the WFS1 gene.</strong> J. Med. Genet. 43: 435-440, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16648378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16648378</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16648378[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/10.1136/jmg.2005.034892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16648378">Eiberg et al. (2006)</a> analyzed the candidate gene WFS1 and identified a missense mutation (E864K; <a href="#0020">606201.0020</a>) in affected individuals. The mutation was not found in unaffected family members or in 2 family members who had only isolated congenital hearing impairment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16648378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 60-year-old French man with congenital hearing impairment and T2D and his 81-year-old mother with deafness, diabetes, and optic atrophy, both of whom were known to be negative for the common mtDNA mutations associated with the maternally inherited diabetes-deafness syndrome (MIDD; <a href="/entry/520000">520000</a>), <a href="#31" class="mim-tip-reference" title="Valero, R., Bannwarth, S., Roman, S., Paquis-Flucklinger, V., Vialettes, B. <strong>Autosomal dominant transmission of diabetes and congenital hearing impairment secondary to a missense mutation in the WFS1 gene.</strong> Diabet. Med. 25: 657-661, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18544103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18544103</a>] [<a href="https://doi.org/10.1111/j.1464-5491.2008.02448.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18544103">Valero et al. (2008)</a> identified heterozygosity for the E864K mutation in the WFS1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18544103" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 affected members of a Dutch family with deafness and optic neuropathy in whom screening of the OPA1 gene (<a href="/entry/605290">605290</a>) and mtDNA screening for the 3 most frequent Leber optic atrophy (<a href="/entry/535000">535000</a>) mutations were both negative, <a href="#17" class="mim-tip-reference" title="Hogewind, B. F. T., Pennings, R. J. E., Hol, F. A., Kunst, H. P. M., Hoefsloot, E. H., Cruysberg, J. R. M., Cremers, C. W. R. J. <strong>Autosomal dominant optic neuropathy and sensorineural hearing loss associated with a novel mutation of WFS1.</strong> Molec. Vis. 16: 26-35, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20069065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20069065</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20069065[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="20069065">Hogewind et al. (2010)</a> identified heterozygosity for a missense mutation in the WFS1 gene (K836N; <a href="#0027">606201.0027</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20069065" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Rendtorff, N. D., Lodahl, M., Boulahbel, H., Johansen, I. R., Pandya, A., Welch, K. O., Norris, V. W., Arnos, K. S., Bitner-Glindzicz, M., Emery, S. B., Mets, M. B., Fagerheim, T., Eriksson, K., Hansen, L., Bruhn, H., Moller, C., Lindholm, S., Ensgaard, S., Lesperance, M. M., Tranebjaerg, L. <strong>Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment.</strong> Am. J. Med. Genet. 155A: 1298-1313, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21538838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21538838</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21538838[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/10.1002/ajmg.a.33970" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21538838">Rendtorff et al. (2011)</a> analyzed the WFS1 gene in 15 probands with deafness and optic atrophy who were known to be negative for mutation in the OPA1 and TIMM8A (<a href="/entry/300356">300356</a>) genes, and identified heterozygosity for the same missense mutation in the WFS1 gene (A684V; <a href="#0028">606201.0028</a>) in 6 probands. Two additional probands were heterozygous for 2 different WFS1 missense mutations (see, e.g., <a href="#0031">606201.0031</a>). In 7 of the 8 mutation-positive families, there were spouses with isolated sensorineural hearing loss (SNHL); analysis of the GJB2 gene (<a href="/entry/121011">121011</a>) revealed that 3 of the probands who were heterozygous for mutation in WFS1 also carried a known SNHL-related mutation in the GJB2 gene (<a href="/entry/121011#0001">121011.0001</a> or <a href="/entry/121011#0005">121011.0005</a>), inherited from a deaf parent who did not have optic atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21538838" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Cataract 41</em></strong></p><p>
|
|
In an affected member of a 4-generation family of Irish descent segregating autosomal dominant congenital nuclear cataract mapping to chromosome 4p16.1 (CTRCT41; <a href="/entry/116400">116400</a>), <a href="#1" class="mim-tip-reference" title="Berry, V., Gregory-Evans, C., Emmett, W., Waseem, N., Raby, J., Prescott, D., Moore, A. T., Bhattacharya, S. S. <strong>Wolfram gene (WFS1) mutation causes autosomal dominant congenital nuclear cataract in humans.</strong> Europ. J. Hum. Genet. 21: 1356-1360, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23531866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23531866</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23531866[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2013.52" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23531866">Berry et al. (2013)</a> performed exome sequencing and identified heterozygosity for a missense mutation in the WFS1 gene (<a href="#0032">606201.0032</a>). Direct genomic sequencing confirmed that the mutation cosegregated completely with disease in the family. Screening of the WFS1 gene in a panel of 50 unrelated individuals with autosomal dominant cataract did not reveal any other mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23531866" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Association with Type 2 Diabetes Mellitus</em></strong></p><p>
|
|
<a href="#27" class="mim-tip-reference" title="Sandhu, M. S., Weedon, M. N., Fawcett, K. A., Wasson, J., Debenham, S. L., Daly, A., Lango, H., Frayling, T. M., Neumann, R. J., Sherva, R., Blech, I., Pharoah, P. D., and 12 others. <strong>Common variants in WFS1 confer risk of type 2 diabetes.</strong> Nature Genet. 39: 951-953, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17603484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17603484</a>] [<a href="https://doi.org/10.1038/ng2067" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17603484">Sandhu et al. (2007)</a> conducted a gene-centric association study for type 2 diabetes mellitus (T2D; <a href="/entry/125853">125853</a>) in multiple large cohorts and identified 2 SNPs located in the WFS1 gene, <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10010131;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs10010131</a> (<a href="#0021">606201.0021</a>) and <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs6446482;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs6446482</a> (<a href="/entry/602201#0022">602201.0022</a>), that were strongly associated with diabetes risk (P = 1.4 x 10(-7) and P = 3.4 x 10(-7), respectively, in the pooled study set). The risk allele was the major allele for both SNPs, with a frequency of 60% for both. The authors noted that both are intronic, with no obvious evidence for biologic function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17603484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#19" class="mim-tip-reference" title="Ishihara, H., Takeda, S., Tamura, A., Takahashi, R., Yamaguchi, S., Takei, D., Yamada, T., Inoue, H., Soga, H., Katagiri, H., Tanizawa, Y., Oka, Y. <strong>Disruption of the WFS1 gene in mice causes progressive beta-cell loss and impaired stimulus-secretion coupling in insulin secretion.</strong> Hum. Molec. Genet. 13: 1159-1170, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15056606/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15056606</a>] [<a href="https://doi.org/10.1093/hmg/ddh125" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15056606">Ishihara et al. (2004)</a> disrupted the wfs1 gene in mice. The mutant mice developed glucose intolerance or overt diabetes due to insufficient insulin (see <a href="/entry/176730">176730</a>) secretion in vivo. Islets isolated from mutant mice exhibited decreased insulin secretion in response to glucose. The defective insulin secretion was accompanied by reduced cellular calcium responses to the secretagogue. Immunohistochemical analyses demonstrated progressive beta-cell loss in mutant mice, while alpha cells, which barely express WFS1 protein, were preserved. Furthermore, isolated islets from mutant mice exhibited increased apoptosis, at high concentration of glucose or with exposure to endoplasmic reticulum stress inducers. The authors suggested that WFS1 protein may play an important role in both stimulus-secretion coupling for insulin exocytosis and maintenance of beta-cell mass. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15056606" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>32 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/606201" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=606201[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 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, 2-BP DEL, 2812TC
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs863224268 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs863224268;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=rs863224268" 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=rs863224268" 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=RCV000199613 OR RCV001668365 OR RCV005042421" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000199613, RCV001668365, RCV005042421" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000199613...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected sibs with Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>) in a consanguineous Japanese family, <a href="#18" class="mim-tip-reference" title="Inoue, H., Tanizawa, Y., Wasson, J., Behn, P., Kalidas, K., Bernal-Mizrachi, E., Meuckler, M., Marshall, H., Donis-Keller, H., Crock, P., Rogers, D., Mikuni, M., Kumashiro, H., Higashi, K., Sobue, G., Oka, Y., Permutt, M. A. <strong>A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).</strong> Nature Genet. 20: 143-148, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771706</a>] [<a href="https://doi.org/10.1038/2441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9771706">Inoue et al. (1998)</a> found a TC deletion at position 2812 in the WFS1 sequence. The deletion was predicted to cause a frameshift at codon 882; they referred to the mutation as del882fs/ter937. The normal stop codon at 891 was absent and a new downstream termination codon had been introduced. The predicted protein contained 937 amino acids, 47 more than the normal protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9771706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, 15-BP DEL, NT1685
|
|
</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> rs781262017 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs781262017;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/rs781262017?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=rs781262017" 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=rs781262017" 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=RCV001941578 OR RCV002274237 OR RCV002507696 OR RCV003336476" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001941578, RCV002274237, RCV002507696, RCV003336476" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001941578...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a consanguineous Japanese family segregating Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>), <a href="#18" class="mim-tip-reference" title="Inoue, H., Tanizawa, Y., Wasson, J., Behn, P., Kalidas, K., Bernal-Mizrachi, E., Meuckler, M., Marshall, H., Donis-Keller, H., Crock, P., Rogers, D., Mikuni, M., Kumashiro, H., Higashi, K., Sobue, G., Oka, Y., Permutt, M. A. <strong>A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).</strong> Nature Genet. 20: 143-148, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771706</a>] [<a href="https://doi.org/10.1038/2441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9771706">Inoue et al. (1998)</a> demonstrated that 4 affected sibs were homozygous for a 15-bp deletion in the WFS1 gene resulting in deletion of 5 amino acids, tyr-val-tyr-leu-leu, beginning with residue 508. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9771706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, PRO724LEU (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937890;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs28937890</a>)
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28937890 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937890;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/rs28937890?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=rs28937890" 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=rs28937890" 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=RCV000004767 OR RCV000756934" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004767, RCV000756934" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004767...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese family segregating Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>), <a href="#18" class="mim-tip-reference" title="Inoue, H., Tanizawa, Y., Wasson, J., Behn, P., Kalidas, K., Bernal-Mizrachi, E., Meuckler, M., Marshall, H., Donis-Keller, H., Crock, P., Rogers, D., Mikuni, M., Kumashiro, H., Higashi, K., Sobue, G., Oka, Y., Permutt, M. A. <strong>A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).</strong> Nature Genet. 20: 143-148, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771706</a>] [<a href="https://doi.org/10.1038/2441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9771706">Inoue et al. (1998)</a> demonstrated that affected members were homozygous for a 2341C-T transition resulting in a pro724-to-leu (P724L) amino acid substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9771706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, GLY695VAL (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937891;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs28937891</a>)
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28937891 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937891;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/rs28937891?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=rs28937891" 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=rs28937891" 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=RCV000004768 OR RCV005031390 OR RCV005089167" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004768, RCV005031390, RCV005089167" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004768...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a European family, <a href="#18" class="mim-tip-reference" title="Inoue, H., Tanizawa, Y., Wasson, J., Behn, P., Kalidas, K., Bernal-Mizrachi, E., Meuckler, M., Marshall, H., Donis-Keller, H., Crock, P., Rogers, D., Mikuni, M., Kumashiro, H., Higashi, K., Sobue, G., Oka, Y., Permutt, M. A. <strong>A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).</strong> Nature Genet. 20: 143-148, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771706</a>] [<a href="https://doi.org/10.1038/2441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9771706">Inoue et al. (1998)</a> demonstrated that 3 sibs with Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>) were compound heterozygous for a 2254G-T transversion resulting in a gly695-to-val (G695V) amino acid substitution (inherited from the father); and a 2114G-A transition resulting in a trp648-to-ter (W648X; <a href="#0005">606201.0005</a>) termination of the protein, predicted to lack 242 amino acids of the C terminus (inherited from the mother). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9771706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, TRP648TER
|
|
</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> rs104893879 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893879;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/rs104893879?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=rs104893879" 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=rs104893879" 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=RCV000004769 OR RCV003114176" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004769, RCV003114176" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004769...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the trp648-to-ter (W648X) mutation in the WFS1 gene that was found in compound heterozygous state in sibs with Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>) by <a href="#18" class="mim-tip-reference" title="Inoue, H., Tanizawa, Y., Wasson, J., Behn, P., Kalidas, K., Bernal-Mizrachi, E., Meuckler, M., Marshall, H., Donis-Keller, H., Crock, P., Rogers, D., Mikuni, M., Kumashiro, H., Higashi, K., Sobue, G., Oka, Y., Permutt, M. A. <strong>A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).</strong> Nature Genet. 20: 143-148, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771706</a>] [<a href="https://doi.org/10.1038/2441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9771706">Inoue et al. (1998)</a>, see <a href="#0004">606201.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9771706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, PRO504LEU (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937892;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs28937892</a>)
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28937892 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937892;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/rs28937892?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=rs28937892" 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=rs28937892" 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=RCV000004770 OR RCV001387727 OR RCV002243622 OR RCV002496259 OR RCV004737135" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004770, RCV001387727, RCV002243622, RCV002496259, RCV004737135" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004770...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Australian family, <a href="#18" class="mim-tip-reference" title="Inoue, H., Tanizawa, Y., Wasson, J., Behn, P., Kalidas, K., Bernal-Mizrachi, E., Meuckler, M., Marshall, H., Donis-Keller, H., Crock, P., Rogers, D., Mikuni, M., Kumashiro, H., Higashi, K., Sobue, G., Oka, Y., Permutt, M. A. <strong>A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).</strong> Nature Genet. 20: 143-148, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771706</a>] [<a href="https://doi.org/10.1038/2441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9771706">Inoue et al. (1998)</a> found apparent homozygosity for a 1681C-T transition (pro504 to leu; P504L) of the WFS1 gene in 3 sibs with Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>). The father was shown to be heterozygous for 1681C-T, but the mother was homozygous 1681C. An unaffected child appeared to be homozygous for 1681C. The mother's chromosome 4, inherited by each child, was thought to harbor a microscopic deletion for WFS1, making the affected offspring hemizygous for the P504L mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9771706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, 7-BP INS, NT1610
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs727503745 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs727503745;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=rs727503745" 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=rs727503745" 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=RCV000152660 OR RCV002273965" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000152660, RCV002273965" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000152660...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 10-year-old Saudi Arabian child with Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>), born to first-cousin parents, <a href="#18" class="mim-tip-reference" title="Inoue, H., Tanizawa, Y., Wasson, J., Behn, P., Kalidas, K., Bernal-Mizrachi, E., Meuckler, M., Marshall, H., Donis-Keller, H., Crock, P., Rogers, D., Mikuni, M., Kumashiro, H., Higashi, K., Sobue, G., Oka, Y., Permutt, M. A. <strong>A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).</strong> Nature Genet. 20: 143-148, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771706</a>] [<a href="https://doi.org/10.1038/2441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9771706">Inoue et al. (1998)</a> found homozygosity for a 7-bp repeat insertion at nucleotide 1610 (CTGAAGG), resulting in a predicted frameshift and premature termination of the protein at codon 544. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9771706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, 9-BP DEL, NT1380
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1578609780 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1578609780;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=rs1578609780" 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=rs1578609780" 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=RCV000004772" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004772" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004772</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#28" class="mim-tip-reference" title="Strom, T. M., Hortnagel, K., Hofmann, S., Gekeler, F., Scharfe, C., Rabl, W., Gerbitz, K. D., Meitinger, T. <strong>Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein.</strong> Hum. Molec. Genet. 7: 2021-2028, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9817917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9817917</a>] [<a href="https://doi.org/10.1093/hmg/7.13.2021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9817917">Strom et al. (1998)</a> found a 9-bp deletion in exon 8 of the WFS1 gene in a 22-year-old female with Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>). The deletion began at nucleotide 1380, counting from the first base of the start codon, and was present in homozygous state. The patient had onset of diabetes mellitus and diabetes insipidus at 6 years of age and also had progressive optic atrophy, abnormal audiogram, renal tract abnormalities, retarded sexual maturation, ataxia and nystagmus, and depression. A sister with the same mutation had onset of diabetes mellitus at 4 years of age, and at the age of 11 years had renal tract abnormalities as the only additional feature. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9817917" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, 460, G-A, +1
|
|
</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> rs1191510461 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1191510461;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/rs1191510461?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=rs1191510461" 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=rs1191510461" 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=RCV000004773 OR RCV001588798" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004773, RCV001588798" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004773...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a brother and sister with Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>), <a href="#28" class="mim-tip-reference" title="Strom, T. M., Hortnagel, K., Hofmann, S., Gekeler, F., Scharfe, C., Rabl, W., Gerbitz, K. D., Meitinger, T. <strong>Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein.</strong> Hum. Molec. Genet. 7: 2021-2028, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9817917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9817917</a>] [<a href="https://doi.org/10.1093/hmg/7.13.2021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9817917">Strom et al. (1998)</a> found homozygosity for a splicing mutation in the WFS1 gene: 460+1G-A in the 5-prime splice signal of exon 4. In the brother and sister, diabetes mellitus began at ages 10 and 9 years, progressive optic atrophy at 14 and 12 years, abnormal audiogram at 13 and 17 years, and diabetes insipidus at 15 and 15 years, respectively. Renal tract abnormalities were present only in the brother, who at the age of 17 years showed retarded sexual maturation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9817917" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, GLN226TER
|
|
</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> rs104893880 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893880;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/rs104893880?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=rs104893880" 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=rs104893880" 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=RCV000004774" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004774" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004774</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 25-year-old female patient with Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>), <a href="#28" class="mim-tip-reference" title="Strom, T. M., Hortnagel, K., Hofmann, S., Gekeler, F., Scharfe, C., Rabl, W., Gerbitz, K. D., Meitinger, T. <strong>Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein.</strong> Hum. Molec. Genet. 7: 2021-2028, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9817917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9817917</a>] [<a href="https://doi.org/10.1093/hmg/7.13.2021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9817917">Strom et al. (1998)</a> found compound heterozygosity for 2 nonsense mutations in the WFS1 gene: gln226 to ter (Q226X) and gln819 to ter (Q819X; <a href="#0011">606201.0011</a>). These mutations were located in exons 6 and 8, respectively. The patient had onset of diabetes mellitus and diabetes insipidus at 7 years of age; progressive optic atrophy began at 9 years, abnormal audiogram at 22 years, and renal tract abnormalities at 24 years. She also had ataxia and nystagmus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9817917" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, GLN819TER
|
|
</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> rs104893881 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893881;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/rs104893881?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=rs104893881" 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=rs104893881" 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=RCV000004775" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004775" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004775</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the gln819-to-ter (Q819X) mutation in the WFS1 gene that was found in compound heterozygous state in a patient with Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>) by <a href="#28" class="mim-tip-reference" title="Strom, T. M., Hortnagel, K., Hofmann, S., Gekeler, F., Scharfe, C., Rabl, W., Gerbitz, K. D., Meitinger, T. <strong>Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein.</strong> Hum. Molec. Genet. 7: 2021-2028, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9817917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9817917</a>] [<a href="https://doi.org/10.1093/hmg/7.13.2021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9817917">Strom et al. (1998)</a>, see <a href="#0010">606201.0010</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9817917" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, 4-BP DEL, NT2648
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs797045076 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797045076;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=rs797045076" 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=rs797045076" 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=RCV000191146 OR RCV000200365 OR RCV001536011" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000191146, RCV000200365, RCV001536011" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000191146...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#13" class="mim-tip-reference" title="Hardy, C., Khanim, F., Torres, R., Scott-Brown, M., Seller, A., Poulton, J., Collier, D., Kirk, J., Polymeropoulos, M., Latif, F., Barrett, T. <strong>Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1.</strong> Am. J. Hum. Genet. 65: 1279-1290, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10521293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10521293</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10521293[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/10.1086/302609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10521293">Hardy et al. (1999)</a> and <a href="#25" class="mim-tip-reference" title="Sam, W., Qin, H., Crawford, B., Yue, D., Yu, S. <strong>Homozygosity for a 4-bp deletion in a patient with Wolfram syndrome suggesting possible phenotype and genotype correlation. (Letter)</strong> Clin. Genet. 59: 136-138, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11260218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11260218</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2001.590214.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11260218">Sam et al. (2001)</a> described Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>) with a distinctive phenotype, namely, central respiratory failure: the patients were homozygous for a 4-bp (TCTT) deletion at position 2648-2651 in exon 8 of the WFS1 gene. The deletion caused loss of codon 883 and a frameshift, producing a 949-amino acid WFS1 protein, which was 59 amino acids longer than normal. The mutation changed the last 7 amino acids of the C terminus of the protein, leaving the transmembrane domains intact. In the patient with the 4-bp deletion reported by <a href="#13" class="mim-tip-reference" title="Hardy, C., Khanim, F., Torres, R., Scott-Brown, M., Seller, A., Poulton, J., Collier, D., Kirk, J., Polymeropoulos, M., Latif, F., Barrett, T. <strong>Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1.</strong> Am. J. Hum. Genet. 65: 1279-1290, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10521293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10521293</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10521293[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/10.1086/302609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10521293">Hardy et al. (1999)</a>, there was severe brainstem atrophy and central respiratory failure requiring tracheostomy. Her affected sister had died at age 28 from brainstem atrophy and central respiratory failure. Five patients (from 3 families) who were heterozygous for the 4-bp deletion did not have respiratory failure. The 33-year-old patient reported by <a href="#25" class="mim-tip-reference" title="Sam, W., Qin, H., Crawford, B., Yue, D., Yu, S. <strong>Homozygosity for a 4-bp deletion in a patient with Wolfram syndrome suggesting possible phenotype and genotype correlation. (Letter)</strong> Clin. Genet. 59: 136-138, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11260218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11260218</a>] [<a href="https://doi.org/10.1034/j.1399-0004.2001.590214.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11260218">Sam et al. (2001)</a> was diagnosed as having diabetes mellitus, a neurogenic bladder, and bilateral optic atrophy at the age of 10, 13, and 15, respectively. Audiometry was normal, and there was no evidence of diabetes insipidus. After an episode of respiratory arrest at age 32, she required intubation, ventilation, and subsequently, tracheostomy. MRI scan showed marked brainstem atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10521293+11260218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, 16-BP DUP, NT409
|
|
</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> rs1362648752 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1362648752;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/rs1362648752?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=rs1362648752" 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=rs1362648752" 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=RCV000004777 OR RCV000499974 OR RCV000778736 OR RCV001385126 OR RCV001542530 OR RCV004814825" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004777, RCV000499974, RCV000778736, RCV001385126, RCV001542530, RCV004814825" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004777...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#11" class="mim-tip-reference" title="Gomez-Zaera, M., Strom, T. M., Rodriguez, B., Estivill, X., Meitinger, T., Nunes, V. <strong>Presence of a major WFS1 mutation in Spanish Wolfram syndrome pedigrees.</strong> Molec. Genet. Metab. 72: 72-81, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11161832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11161832</a>] [<a href="https://doi.org/10.1006/mgme.2000.3107" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11161832">Gomez-Zaera et al. (2001)</a> studied 22 Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>) patients from 16 Spanish families for mutations in the WFS1 coding region by SSCP analysis and direct sequencing. Fifty percent of the pedigrees were found to have a single mutation, 67% in homozygosity and 33% in compound heterozygosity. The authors stated that the mutation is a 16-bp insertion in exon 4 at nucleotide 425 and is predicted to produce an aberrant protein; assuming that no splicing alterations occur, translation will follow until residue 251, where a stop codon is created. The high incidence of this mutation in Spanish families may be explained by a founder effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11161832" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 4 patients from 3 Spanish families with Wolfram syndrome, <a href="#7" class="mim-tip-reference" title="Domenech, E., Gomez-Zaera, M., Nunes, V. <strong>Study of the WFS1 gene and mitochondrial DNA in Spanish Wolfram syndrome families.</strong> Clin. Genet. 65: 463-469, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15151504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15151504</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2004.00249.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15151504">Domenech et al. (2004)</a> identified the 425ins16 mutation, which they referred to as a 16-bp duplication (409dup16). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15151504" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 DOMINANT 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, ALA716THR (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937893;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs28937893</a>)
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28937893 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937893;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/rs28937893?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=rs28937893" 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=rs28937893" 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=RCV000004778 OR RCV000522349 OR RCV000599627" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004778, RCV000522349, RCV000599627" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004778...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#32" class="mim-tip-reference" title="Young, T.-L., Ives, E., Lynch, E., Person, R., Snook, S., MacLaren, L., Cater, T., Griffin, A., Fernandez, B., Lee, M. K., King, M.-C. <strong>Non-syndromic progressive hearing loss DFNA38 is caused by heterozygous missense mutation in the Wolfram syndrome gene WFS1.</strong> Hum. Molec. Genet. 10: 2509-2514, 2001. Note: Erratum: Hum. Molec. Genet. 10: 3111 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709538</a>] [<a href="https://doi.org/10.1093/hmg/10.22.2509" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11709538">Young et al. (2001)</a> described a 6-generation Canadian family with dominantly inherited progressive hearing loss (DFNA6; <a href="/entry/600965">600965</a>), in which affected individuals were heterozygous for a 2146G-A transition in WFS1. The mutation resulted in an ala716-to-thr (A716T) substitution. Affected individuals lacked additional phenotypic features seen in Wolfram syndrome, with the exception of a child who was homozygous for the mutation and also manifested diabetes mellitus by the age of 3 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709538" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 affected members of a 3-generation Japanese family segregating autosomal dominant nonsyndromic low-frequency sensorineural hearing loss, <a href="#10" class="mim-tip-reference" title="Fukuoka, H., Kanda, Y., Ohta, S., Usami, S. <strong>Mutations in the WFS1 gene are a frequent cause of autosomal dominant nonsyndromic low-frequency hearing loss in Japanese.</strong> J. Hum. Genet. 52: 510-515, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17492394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17492394</a>] [<a href="https://doi.org/10.1007/s10038-007-0144-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17492394">Fukuoka et al. (2007)</a> identified heterozygosity for the A716T mutation in the WFS1 gene. The mutation was not found in 3 unaffected family members or in 86 controls. Because the same mutation was previously found in a family of European ancestry, the authors suggested that this might represent a mutation hotspot. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17492394" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 DOMINANT 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, LEU829PRO
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104893883 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893883;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=rs104893883" 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=rs104893883" 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=RCV000004779 OR RCV000726781 OR RCV001267554 OR RCV003155015 OR RCV005041982" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004779, RCV000726781, RCV001267554, RCV003155015, RCV005041982" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004779...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#2" class="mim-tip-reference" title="Bespalova, I. N., Van Camp, G., Bom, S. J. H., Brown, D. J., Cryns, K., DeWan, A. T., Erson, A. E., Flothmann, K., Kunst, H. P. M., Kurnool, P., Sivakumaran, T. A., Cremers, C. W. R. J., Leal, S. M., Burmeister, M., Lesperance, M. M. <strong>Mutations in the Wolfram syndrome 1 gene (WFS1) are a common cause of low frequency sensorineural hearing loss.</strong> Hum. Molec. Genet. 10: 2501-2508, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709537</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11709537[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/10.22.2501" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11709537">Bespalova et al. (2001)</a> described a 3-generation American family with low-frequency sensorineural hearing loss (DFNA6; <a href="/entry/600965">600965</a>). Affected individuals were heterozygous for a T2656C transition in the WFS1 gene, resulting in a leu829-to-pro (L829P) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709537" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 DEAFNESS, AUTOSOMAL DOMINANT 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, THR699MET (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937894;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs28937894</a>)
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28937894 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937894;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=rs28937894" 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=rs28937894" 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=RCV000004780 OR RCV000238945 OR RCV001851653" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004780, RCV000238945, RCV001851653" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004780...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#2" class="mim-tip-reference" title="Bespalova, I. N., Van Camp, G., Bom, S. J. H., Brown, D. J., Cryns, K., DeWan, A. T., Erson, A. E., Flothmann, K., Kunst, H. P. M., Kurnool, P., Sivakumaran, T. A., Cremers, C. W. R. J., Leal, S. M., Burmeister, M., Lesperance, M. M. <strong>Mutations in the Wolfram syndrome 1 gene (WFS1) are a common cause of low frequency sensorineural hearing loss.</strong> Hum. Molec. Genet. 10: 2501-2508, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709537</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11709537[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/10.22.2501" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11709537">Bespalova et al. (2001)</a> and <a href="#4" class="mim-tip-reference" title="Cryns, K., Pfister, M., Pennings, R. J. E., Bom, S. J. H., Flothmann, K., Caethoven, G., Kremer, H., Schatteman, I., Koln, K. A., Toth, T., Kupka, S., Blin, N., Nurnberg, P., Thiele, H., van de Heyning, P. H., Reardon, W., Stephens, D., Cremers, C. W. R. J., Smith, R. J. H., Van Camp, G. <strong>Mutations in the WFS1 gene that cause low-frequency sensorineural hearing loss are small non-inactivating mutations.</strong> Hum. Genet. 110: 389-394, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12073007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12073007</a>] [<a href="https://doi.org/10.1007/s00439-002-0719-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12073007">Cryns et al. (2002)</a> described patients with low-frequency sensorineural hearing loss (DFNA6; <a href="/entry/600965">600965</a>) due to a 2096C-T nucleotide change in exon 8 of the WFS1 gene, predicting a thr699-to-met (T699M) protein change. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12073007+11709537" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 DEAFNESS, AUTOSOMAL DOMINANT 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, GLY831ASP (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937895;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs28937895</a>)
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28937895 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937895;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/rs28937895?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=rs28937895" 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=rs28937895" 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=RCV000004781 OR RCV000521055" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004781, RCV000521055" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004781...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#2" class="mim-tip-reference" title="Bespalova, I. N., Van Camp, G., Bom, S. J. H., Brown, D. J., Cryns, K., DeWan, A. T., Erson, A. E., Flothmann, K., Kunst, H. P. M., Kurnool, P., Sivakumaran, T. A., Cremers, C. W. R. J., Leal, S. M., Burmeister, M., Lesperance, M. M. <strong>Mutations in the Wolfram syndrome 1 gene (WFS1) are a common cause of low frequency sensorineural hearing loss.</strong> Hum. Molec. Genet. 10: 2501-2508, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709537</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11709537[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/10.22.2501" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11709537">Bespalova et al. (2001)</a> and <a href="#4" class="mim-tip-reference" title="Cryns, K., Pfister, M., Pennings, R. J. E., Bom, S. J. H., Flothmann, K., Caethoven, G., Kremer, H., Schatteman, I., Koln, K. A., Toth, T., Kupka, S., Blin, N., Nurnberg, P., Thiele, H., van de Heyning, P. H., Reardon, W., Stephens, D., Cremers, C. W. R. J., Smith, R. J. H., Van Camp, G. <strong>Mutations in the WFS1 gene that cause low-frequency sensorineural hearing loss are small non-inactivating mutations.</strong> Hum. Genet. 110: 389-394, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12073007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12073007</a>] [<a href="https://doi.org/10.1007/s00439-002-0719-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12073007">Cryns et al. (2002)</a> described patients with low-frequency sensorineural hearing loss (DFNA6; <a href="/entry/600965">600965</a>) due to a 2492G-A transition in exon 8 of the WFS1 gene, predicting a gly831-to-asp (G831D) amino acid change. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12073007+11709537" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 DEAFNESS, AUTOSOMAL DOMINANT 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, LYS634THR
|
|
</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> rs104893882 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104893882;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/rs104893882?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=rs104893882" 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=rs104893882" 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=RCV000004782" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004782" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004782</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese family in which 20 members had nonsyndromic low-frequency sensorineural hearing loss (DFNA6; <a href="/entry/600965">600965</a>), <a href="#21" class="mim-tip-reference" title="Komatsu, K., Nakamura, N., Ghadami, M., Matsumoto, N., Kishino, T., Ohta, T., Niikawa, N., Yoshiura, K. <strong>Confirmation of genetic homogeneity of nonsyndromic low-frequency sensorineural hearing loss by linkage analysis and a DFNA6/14 mutation in a Japanese family.</strong> J. Hum. Genet. 47: 395-399, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12181639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12181639</a>] [<a href="https://doi.org/10.1007/s100380200057" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12181639">Komatsu et al. (2002)</a> demonstrated linkage to chromosome 4p16 and found a novel missense mutation, lys634 to thr (K634T), in the WFS1 gene. The mutation was located in the hydrophobic, extracytoplasmic, juxta-transmembrane region of the WFS1 protein. The mutation site was thought to be related to the milder phenotype (lacking tinnitus) in the Japanese family compared with the findings in 6 previously reported patients with WFS1 mutations (<a href="#22" class="mim-tip-reference" title="Lesperance, M. M., Hall, J. W., III, Bess, F. H., Fukushima, K., Jain, P. K., Ploplis, B., San Agustin, T. B., Skarka, H., Smith, R. J. H., Wills, M., Wilcox, E. R. <strong>A gene for autosomal dominant nonsyndromic hereditary hearing impairment maps to 4p16.3.</strong> Hum. Molec. Genet. 4: 1967-1972, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8595423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8595423</a>] [<a href="https://doi.org/10.1093/hmg/4.10.1967" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8595423">Lesperance et al., 1995</a>; <a href="#28" class="mim-tip-reference" title="Strom, T. M., Hortnagel, K., Hofmann, S., Gekeler, F., Scharfe, C., Rabl, W., Gerbitz, K. D., Meitinger, T. <strong>Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein.</strong> Hum. Molec. Genet. 7: 2021-2028, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9817917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9817917</a>] [<a href="https://doi.org/10.1093/hmg/7.13.2021" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9817917">Strom et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9817917+8595423+12181639" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, 16-BP DEL, NT1362
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1730884546 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1730884546;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=rs1730884546" 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=rs1730884546" 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=RCV001172534 OR RCV001873597 OR RCV002274141" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001172534, RCV001873597, RCV002274141" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001172534...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>) patients from 5 different unrelated Italian families, <a href="#3" class="mim-tip-reference" title="Colosimo, A., Guida, V., Rigoli, L., Di Bella, C., De Luca, A., Briuglia, S., Stuppia, L., Salpietro, D. C., Dallapiccolo, B. <strong>Molecular detection of novel WFS1 mutations in patients with Wolfram syndrome by a DHPLC-based assay.</strong> Hum. Mutat. 21: 622-629, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12754709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12754709</a>] [<a href="https://doi.org/10.1002/humu.10215" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12754709">Colosimo et al. (2003)</a> found a 16-bp deletion in the WFS1 gene that removed nucleotides 1362 to 1377, causing a frameshift with premature termination at codon 454. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12754709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="0020" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 WOLFRAM-LIKE SYNDROME, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
DEAFNESS, AUTOSOMAL DOMINANT 6, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, GLU864LYS (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315205;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs74315205</a>)
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs74315205 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315205;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=rs74315205" 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=rs74315205" 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=RCV000004784 OR RCV000020637 OR RCV000523215 OR RCV000599631 OR RCV001528145 OR RCV001544536 OR RCV004794324 OR RCV004797754 OR RCV004814826" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004784, RCV000020637, RCV000523215, RCV000599631, RCV001528145, RCV001544536, RCV004794324, RCV004797754, RCV004814826" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004784...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a 3-generation Danish family with an autosomal dominant Wolfram-like syndrome (WFSL; <a href="/entry/614296">614296</a>), <a href="#8" class="mim-tip-reference" title="Eiberg, H., Hansen, L., Kjer, B., Hansen, T., Pedersen, O., Bille, M., Rosenberg, T., Tranebjaerg, L. <strong>Autosomal dominant optic atrophy associated with hearing impairment and impaired glucose regulation caused by a missense mutation in the WFS1 gene.</strong> J. Med. Genet. 43: 435-440, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16648378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16648378</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16648378[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/10.1136/jmg.2005.034892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16648378">Eiberg et al. (2006)</a> identified heterozygosity for a 2590G-A transition in exon 8 of the WFS1 gene, resulting in a glu864-to-lys (E864K) substitution. Affected individuals had optic atrophy, progressive hearing impairment, and impaired glucose regulation. The mutation was not found in unaffected family members, nor in 2 family members with isolated congenital hearing impairment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16648378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 7 affected members from 2 unrelated Japanese families segregating autosomal dominant nonsyndromic low-frequency sensorineural hearing loss (DFNA6; <a href="/entry/600965">600965</a>), <a href="#10" class="mim-tip-reference" title="Fukuoka, H., Kanda, Y., Ohta, S., Usami, S. <strong>Mutations in the WFS1 gene are a frequent cause of autosomal dominant nonsyndromic low-frequency hearing loss in Japanese.</strong> J. Hum. Genet. 52: 510-515, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17492394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17492394</a>] [<a href="https://doi.org/10.1007/s10038-007-0144-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17492394">Fukuoka et al. (2007)</a> identified heterozygosity for the E864K mutation in the WFS1 gene. The mutation was not found in 3 unaffected family members or in 86 controls. Because the same mutation was previously found in a family of European ancestry, the authors suggested that this might represent a mutation hotspot. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17492394" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 60-year-old French man with congenital hearing impairment and noninsulin-dependent diabetes and his 81-year-old mother with deafness, diabetes, and optic atrophy, <a href="#31" class="mim-tip-reference" title="Valero, R., Bannwarth, S., Roman, S., Paquis-Flucklinger, V., Vialettes, B. <strong>Autosomal dominant transmission of diabetes and congenital hearing impairment secondary to a missense mutation in the WFS1 gene.</strong> Diabet. Med. 25: 657-661, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18544103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18544103</a>] [<a href="https://doi.org/10.1111/j.1464-5491.2008.02448.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18544103">Valero et al. (2008)</a> identified heterozygosity for the E864K mutation in the WFS1 gene. The mutation was not found in 100 French controls. The proband, who did not have optic atrophy or any other manifestations of Wolfram syndrome, also carried a 683G-A transition in exon 6 of WFS1, resulting in an arg228-to-gln (R228Q; <a href="#0026">606201.0026</a>) substitution at a conserved residue that was not found in controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18544103" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0021" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 TYPE 2 DIABETES MELLITUS, ASSOCIATION WITH</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10010131;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs10010131</a>)
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs10010131 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10010131;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/rs10010131?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=rs10010131" 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=rs10010131" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <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> rs6446482 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs6446482;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/rs6446482?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=rs6446482" 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=rs6446482" 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=RCV000004785 OR RCV000038664 OR RCV000273205 OR RCV000325882 OR RCV001513863 OR RCV002225069" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004785, RCV000038664, RCV000273205, RCV000325882, RCV001513863, RCV002225069" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004785...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an association study for type 2 diabetes (T2D; <a href="/entry/125853">125853</a>) involving single-nucleotide polymorphisms (SNPs) in genes with roles in pancreatic beta-cell function, <a href="#27" class="mim-tip-reference" title="Sandhu, M. S., Weedon, M. N., Fawcett, K. A., Wasson, J., Debenham, S. L., Daly, A., Lango, H., Frayling, T. M., Neumann, R. J., Sherva, R., Blech, I., Pharoah, P. D., and 12 others. <strong>Common variants in WFS1 confer risk of type 2 diabetes.</strong> Nature Genet. 39: 951-953, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17603484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17603484</a>] [<a href="https://doi.org/10.1038/ng2067" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17603484">Sandhu et al. (2007)</a> identified association of 2 SNPs in the WFS1 gene, <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10010131;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs10010131</a> and <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs6446482;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs6446482</a> (<a href="#0022">606201.0022</a>), with diabetes risk. Analysis of a pooled study set of 9,533 cases and 11,389 controls achieved a P value of 1.4 x 10(-7) for <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs10010131;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs10010131</a> and a P value of 3.4 x 10(-7) for <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs6446482;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs6446482</a>. Both of these SNPs are intronic, with no obvious evidence for biologic function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17603484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0022" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 TYPE 2 DIABETES MELLITUS, ASSOCIATION WITH</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs6446482;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs6446482</a>)
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs6446482 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs6446482;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/rs6446482?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=rs6446482" 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=rs6446482" 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=RCV000004786 OR RCV000830171 OR RCV000987406 OR RCV001255180 OR RCV001777131" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004786, RCV000830171, RCV000987406, RCV001255180, RCV001777131" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004786...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs6446482;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs6446482</a> in the WFS1 gene that was found in an association study for type 2 diabetes mellitus (T2D; <a href="/entry/125853">125853</a>) by <a href="#27" class="mim-tip-reference" title="Sandhu, M. S., Weedon, M. N., Fawcett, K. A., Wasson, J., Debenham, S. L., Daly, A., Lango, H., Frayling, T. M., Neumann, R. J., Sherva, R., Blech, I., Pharoah, P. D., and 12 others. <strong>Common variants in WFS1 confer risk of type 2 diabetes.</strong> Nature Genet. 39: 951-953, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17603484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17603484</a>] [<a href="https://doi.org/10.1038/ng2067" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17603484">Sandhu et al. (2007)</a>, see <a href="#0021">606201.0021</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17603484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0023" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 DEAFNESS, AUTOSOMAL DOMINANT 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, ARG859GLN
|
|
</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> rs121912618 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912618;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/rs121912618?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=rs121912618" 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=rs121912618" 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=RCV000004787 OR RCV000275899 OR RCV000480362 OR RCV002490313 OR RCV004532289 OR RCV004814827" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004787, RCV000275899, RCV000480362, RCV002490313, RCV004532289, RCV004814827" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004787...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 6 affected members of a family with autosomal dominant sensorineural deafness (DFNA6; <a href="/entry/600965">600965</a>), <a href="#14" class="mim-tip-reference" title="Hildebrand, M. S., Sorensen, J. L., Jensen, M., Kimberling, W. J., Smith, R. J. H. <strong>Autoimmune disease in a DFNA6/14/38 family carrying a novel missense mutation in WFS1.</strong> Am. J. Med. Genet. 146A: 2258-2265, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18688868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18688868</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18688868[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/10.1002/ajmg.a.32449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18688868">Hildebrand et al. (2008)</a> identified a heterozygous 2576G-A transition in exon 8 of the WFS1 gene, resulting in an arg859-to-gln (R859Q) substitution in the C-terminal domain. Two affected females had concurrent Crohn disease (see <a href="/entry/266600">266600</a>) and Graves disease (<a href="/entry/275000">275000</a>), respectively. <a href="#14" class="mim-tip-reference" title="Hildebrand, M. S., Sorensen, J. L., Jensen, M., Kimberling, W. J., Smith, R. J. H. <strong>Autoimmune disease in a DFNA6/14/38 family carrying a novel missense mutation in WFS1.</strong> Am. J. Med. Genet. 146A: 2258-2265, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18688868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18688868</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18688868[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/10.1002/ajmg.a.32449" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18688868">Hildebrand et al. (2008)</a> noted that polymorphisms in the WFS1 gene (see, e.g., <a href="#0021">606201.0021</a>) had been associated with autoimmune disease, and suggested that the autoimmune disease in the 2 family members may be related to variants in the WFS1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18688868" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0024" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, VAL707PHE AND 1-BP DEL, 2819C
|
|
</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> rs71524377 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs71524377;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/rs71524377?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=rs71524377" 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=rs71524377" 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=RCV000023510 OR RCV003553890 OR RCV003778168" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023510, RCV003553890, RCV003778168" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023510...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 20 Lebanese patients from 8 families ascertained with juvenile-onset insulin-dependent diabetes (<a href="/entry/222100">222100</a>), <a href="#33" class="mim-tip-reference" title="Zalloua, P. A., Azar, S. T., Delepine, M., Makhoul, N. J., Blanc, H., Sanyoura, M., Lavergne, A., Stankov, K., Lemainque, A., Baz, P., Julier, C. <strong>WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon.</strong> Hum. Molec. Genet. 17: 4012-4021, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18806274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18806274</a>] [<a href="https://doi.org/10.1093/hmg/ddn304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18806274">Zalloua et al. (2008)</a> identified homozygosity for a complex mutation in exon 8 of the WFS1 gene, which they designated WFS1(LIB), consisting of a 2289G-A transition, resulting in a val707-to-phe (V707F) substitution, and a 1-bp del (2819delC), resulting in a frameshift predicted to cause premature termination. The mutations were in complete linkage disequilibrium and were consistently associated with the same haplotype. Eight of the 20 patients were diagnosed with Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>), whereas 10 had only nonsyndromic nonautoimmune diabetes mellitus (DM); the remaining 2 patients were given an initial diagnosis of nonsyndromic DM that was revised to WFS when they developed optic atrophy during the course of the study. Another Lebanese patient with nonsyndromic DM was found to be compound heterozygous for the complex mutation and an 8-bp deletion in exon 8 of the WFS1 gene (<a href="#0025">606201.0025</a>), resulting in a frameshift predicted to cause premature termination. This frameshift mutation (Phe646fs708Ter) was also found in 4 patients with a diagnosis of Wolfram syndrome. <a href="#33" class="mim-tip-reference" title="Zalloua, P. A., Azar, S. T., Delepine, M., Makhoul, N. J., Blanc, H., Sanyoura, M., Lavergne, A., Stankov, K., Lemainque, A., Baz, P., Julier, C. <strong>WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon.</strong> Hum. Molec. Genet. 17: 4012-4021, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18806274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18806274</a>] [<a href="https://doi.org/10.1093/hmg/ddn304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18806274">Zalloua et al. (2008)</a> noted that follow-up of these WFS1-mutated nonsyndromic DM patients or a specific study of adult patient populations would be needed to determine whether a subset of the WFS1(LIB) patients are exempted from extrapancreatic manifestations during their lifetime. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18806274" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="0025" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, 8-BP DEL, NT2106
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs71524374 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs71524374;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=rs71524374" 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=rs71524374" 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=RCV000023511" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023511" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023511</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 8-bp deletion in the WFS1 gene that was found in patients with Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>) or nonsyndromic nonautoimmune diabetes mellitus by <a href="#33" class="mim-tip-reference" title="Zalloua, P. A., Azar, S. T., Delepine, M., Makhoul, N. J., Blanc, H., Sanyoura, M., Lavergne, A., Stankov, K., Lemainque, A., Baz, P., Julier, C. <strong>WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon.</strong> Hum. Molec. Genet. 17: 4012-4021, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18806274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18806274</a>] [<a href="https://doi.org/10.1093/hmg/ddn304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18806274">Zalloua et al. (2008)</a>, see <a href="#0024">606201.0024</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18806274" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0026" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 WOLFRAM-LIKE SYNDROME, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, ARG228GLN
|
|
</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> rs150771247 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs150771247;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/rs150771247?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=rs150771247" 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=rs150771247" 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=RCV000023512 OR RCV000200201 OR RCV000515386 OR RCV000724125 OR RCV001155463 OR RCV001155464 OR RCV004537488 OR RCV004816299" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023512, RCV000200201, RCV000515386, RCV000724125, RCV001155463, RCV001155464, RCV004537488, RCV004816299" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023512...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg228-to-gln (R228Q) mutation in the WFS1 gene that was found in compound heterozygous state in a patient with congenital hearing impairment and noninsulin-dependent diabetes (see WFSL, <a href="/entry/614296">614296</a>) by <a href="#31" class="mim-tip-reference" title="Valero, R., Bannwarth, S., Roman, S., Paquis-Flucklinger, V., Vialettes, B. <strong>Autosomal dominant transmission of diabetes and congenital hearing impairment secondary to a missense mutation in the WFS1 gene.</strong> Diabet. Med. 25: 657-661, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18544103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18544103</a>] [<a href="https://doi.org/10.1111/j.1464-5491.2008.02448.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18544103">Valero et al. (2008)</a>, see <a href="#0020">606201.0020</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18544103" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0027" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 WOLFRAM-LIKE SYNDROME, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, LYS836ASN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs876657675 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs876657675;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=rs876657675" 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=rs876657675" 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=RCV000023513 OR RCV000219504" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023513, RCV000219504" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023513...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected members of a Dutch family segregating autosomal dominant deafness and optic neuropathy (WFSL; <a href="/entry/614296">614296</a>), <a href="#17" class="mim-tip-reference" title="Hogewind, B. F. T., Pennings, R. J. E., Hol, F. A., Kunst, H. P. M., Hoefsloot, E. H., Cruysberg, J. R. M., Cremers, C. W. R. J. <strong>Autosomal dominant optic neuropathy and sensorineural hearing loss associated with a novel mutation of WFS1.</strong> Molec. Vis. 16: 26-35, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20069065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20069065</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20069065[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="20069065">Hogewind et al. (2010)</a> identified heterozygosity for a 2508G-C transversion in exon 8 of the WFS1 gene, resulting in a lys836-to-asn (K836N) substitution at a highly conserved residue within a conserved region of the protein. The mutation was not found in unaffected family members or in 200 European chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20069065" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0028" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 WOLFRAM-LIKE SYNDROME, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
WOLFRAM SYNDROME 1, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, ALA684VAL
|
|
</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> rs387906930 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906930;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/rs387906930?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=rs387906930" 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=rs387906930" 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=RCV000023514 OR RCV000023515 OR RCV000200668 OR RCV000605882 OR RCV000623116 OR RCV001542531 OR RCV002280094 OR RCV004808555 OR RCV004814922" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023514, RCV000023515, RCV000200668, RCV000605882, RCV000623116, RCV001542531, RCV002280094, RCV004808555, RCV004814922" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023514...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 6 unrelated families segregating autosomal dominant hearing loss and optic atrophy (WFSL; <a href="/entry/614296">614296</a>), including the Swedish family originally reported by <a href="#26" class="mim-tip-reference" title="Samuelson, A. <strong>Familjart upptradande synnervsatrofi och dovhet.</strong> Nord. Med. 6: 769-772, 1940."None>Samuelson (1940)</a>, <a href="#24" class="mim-tip-reference" title="Rendtorff, N. D., Lodahl, M., Boulahbel, H., Johansen, I. R., Pandya, A., Welch, K. O., Norris, V. W., Arnos, K. S., Bitner-Glindzicz, M., Emery, S. B., Mets, M. B., Fagerheim, T., Eriksson, K., Hansen, L., Bruhn, H., Moller, C., Lindholm, S., Ensgaard, S., Lesperance, M. M., Tranebjaerg, L. <strong>Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment.</strong> Am. J. Med. Genet. 155A: 1298-1313, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21538838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21538838</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21538838[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/10.1002/ajmg.a.33970" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21538838">Rendtorff et al. (2011)</a> identified heterozygosity for a 2051C-T transition in exon 8 of the WFS1 gene, resulting in an ala684-to-val (A684V) substitution at a highly conserved residue in the hydrophilic C terminus. The mutation was not found in 298 ethnically matched control chromosomes. Haplotype analysis suggested that the A684V mutation arose independently in the families studied and may thus represent a mutation hotspot. In 5 of the 6 families, there were spouses with isolated deafness, prompting analysis of the GJB2 gene (<a href="/entry/121011">121011</a>), which revealed that 2 of the probands also carried known SNHL-related mutations in the GJB2 gene (<a href="/entry/121011#0001">121011.0001</a> or <a href="/entry/121011#0005">121011.0005</a>) inherited from a deaf parent who did not have optic atrophy. In 1 family, the proband's asymptomatic wife carried a 3-bp deletion (1243delGTC; <a href="#0029">606201.0029</a>) in the WFS1 gene, resulting in deletion of val415 (V415del); their 2 children were compound heterozygotes for the deletion and A684V mutation, and both were diagnosed with Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>) based on juvenile-onset diabetes mellitus, optic atrophy, bilateral profound sensorineural hearing loss from birth or infancy, and congenital cataracts. Functional expression analysis in transiently transfected HEK cells demonstrated that both A684V and V415del greatly reduced protein expression compared to wildtype. <a href="#24" class="mim-tip-reference" title="Rendtorff, N. D., Lodahl, M., Boulahbel, H., Johansen, I. R., Pandya, A., Welch, K. O., Norris, V. W., Arnos, K. S., Bitner-Glindzicz, M., Emery, S. B., Mets, M. B., Fagerheim, T., Eriksson, K., Hansen, L., Bruhn, H., Moller, C., Lindholm, S., Ensgaard, S., Lesperance, M. M., Tranebjaerg, L. <strong>Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment.</strong> Am. J. Med. Genet. 155A: 1298-1313, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21538838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21538838</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21538838[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/10.1002/ajmg.a.33970" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21538838">Rendtorff et al. (2011)</a> noted that A684V had previously been reported in an Italian patient with Wolfram syndrome (<a href="#30" class="mim-tip-reference" title="Tessa, A., Carbone, I., Matteoli, M. C., Bruno, C., Patrono, C., Patera, I. P., De Luca, F., Lorini, R., Santorelli, F. M. <strong>Identification of novel WFS1 mutations in Italian children with Wolfram syndrome.</strong> Hum. Mutat. 17: 348-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11295831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11295831</a>] [<a href="https://doi.org/10.1002/humu.32" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11295831">Tessa et al., 2001</a>) in compound heterozygosity with a 4-bp deletion (1387delCTCT; <a href="#0030">606201.0030</a>) in the WFS1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21538838+11295831" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0029" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, 3-BP DEL, VAL415DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs863224265 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs863224265;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=rs863224265" 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=rs863224265" 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=RCV000199829 OR RCV000611263 OR RCV001843422 OR RCV001849340 OR RCV002478696 OR RCV004541271" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000199829, RCV000611263, RCV001843422, RCV001849340, RCV002478696, RCV004541271" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000199829...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 3-bp deletion in the WFS1 gene (1243delGTC) that was found in compound heterozygous state in sibs with Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>) by <a href="#24" class="mim-tip-reference" title="Rendtorff, N. D., Lodahl, M., Boulahbel, H., Johansen, I. R., Pandya, A., Welch, K. O., Norris, V. W., Arnos, K. S., Bitner-Glindzicz, M., Emery, S. B., Mets, M. B., Fagerheim, T., Eriksson, K., Hansen, L., Bruhn, H., Moller, C., Lindholm, S., Ensgaard, S., Lesperance, M. M., Tranebjaerg, L. <strong>Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment.</strong> Am. J. Med. Genet. 155A: 1298-1313, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21538838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21538838</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21538838[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/10.1002/ajmg.a.33970" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21538838">Rendtorff et al. (2011)</a>, see <a href="#0028">606201.0028</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21538838" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0030" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, 4-BP DEL, 1387CTCT
|
|
</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> rs760337383 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs760337383;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/rs760337383?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=rs760337383" 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=rs760337383" 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=RCV000494474 OR RCV000778738 OR RCV001672804 OR RCV002252138 OR RCV002481565 OR RCV004535551 OR RCV004816729" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000494474, RCV000778738, RCV001672804, RCV002252138, RCV002481565, RCV004535551, RCV004816729" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000494474...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 4-bp deletion in the WFS1 gene (1387delCTCT) that was found in compound heterozygous state in a patient with Wolfram syndrome (WFS1; <a href="/entry/222300">222300</a>) by <a href="#30" class="mim-tip-reference" title="Tessa, A., Carbone, I., Matteoli, M. C., Bruno, C., Patrono, C., Patera, I. P., De Luca, F., Lorini, R., Santorelli, F. M. <strong>Identification of novel WFS1 mutations in Italian children with Wolfram syndrome.</strong> Hum. Mutat. 17: 348-349, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11295831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11295831</a>] [<a href="https://doi.org/10.1002/humu.32" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11295831">Tessa et al. (2001)</a>, see <a href="#0028">606201.0028</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11295831" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0031" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 WOLFRAM-LIKE SYNDROME, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, GLY780SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906931 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906931;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=rs387906931" 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=rs387906931" 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=RCV000023518 OR RCV001762055" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023518, RCV001762055" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023518...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a sister and brother and their affected mother from a Caucasian UK family segregating autosomal dominant hearing loss and optic atrophy (WFSL; <a href="/entry/614296">614296</a>), <a href="#24" class="mim-tip-reference" title="Rendtorff, N. D., Lodahl, M., Boulahbel, H., Johansen, I. R., Pandya, A., Welch, K. O., Norris, V. W., Arnos, K. S., Bitner-Glindzicz, M., Emery, S. B., Mets, M. B., Fagerheim, T., Eriksson, K., Hansen, L., Bruhn, H., Moller, C., Lindholm, S., Ensgaard, S., Lesperance, M. M., Tranebjaerg, L. <strong>Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment.</strong> Am. J. Med. Genet. 155A: 1298-1313, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21538838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21538838</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21538838[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/10.1002/ajmg.a.33970" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21538838">Rendtorff et al. (2011)</a> identified heterozygosity for a 2338G-A transition in exon 8 of the WFS1 gene, resulting in a gly780-to-ser (G780S) substitution at a conserved residue in the hydrophilic C terminus. The mutation was not found in 298 ethnically matched control chromosomes, and functional analysis in transiently transfected HEK cells demonstrated that G780S mildly decreased protein expression compared to wildtype. The 14-year-old sister was reported to have bilateral prelingual profound hearing loss and optic atrophy, with normal plasma glucose and urine osmolality, and her 9-year-old affected brother had also been diagnosed with autism. Their 48-year-old affected mother also had schizophrenia and had been treated for psychosis; she had an affected brother and sister. The sibs' father, who had isolated sensorineural hearing loss (SNHL), was homozygous for a known SNHL-related mutation in the GJB2 gene (35delG; <a href="/entry/121011#0005">121011.0005</a>), and the sibs were both heterozygous for that mutation as well. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21538838" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0032" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0032 CATARACT 41 (1 family)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
WFS1, GLU462GLY
|
|
</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> rs398123066 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398123066;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/rs398123066?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=rs398123066" 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=rs398123066" 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=RCV000077875 OR RCV004597741" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000077875, RCV004597741" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000077875...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a 4-generation family of Irish descent with congenital nuclear cataract (CTRCT41; <a href="/entry/116400">116400</a>), <a href="#1" class="mim-tip-reference" title="Berry, V., Gregory-Evans, C., Emmett, W., Waseem, N., Raby, J., Prescott, D., Moore, A. T., Bhattacharya, S. S. <strong>Wolfram gene (WFS1) mutation causes autosomal dominant congenital nuclear cataract in humans.</strong> Europ. J. Hum. Genet. 21: 1356-1360, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23531866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23531866</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23531866[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2013.52" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23531866">Berry et al. (2013)</a> identified heterozygosity for a c.1385A-G transition in exon 8 of the WFS1 gene, resulting in a glu462-to-gly (E462G) substitution at a highly conserved residue in the cytoplasmic loop linking transmembrane domains 4 and 5. The mutation was not found in unaffected family members or in 100 white European controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23531866" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Berry2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Berry, V., Gregory-Evans, C., Emmett, W., Waseem, N., Raby, J., Prescott, D., Moore, A. T., Bhattacharya, S. S.
|
|
<strong>Wolfram gene (WFS1) mutation causes autosomal dominant congenital nuclear cataract in humans.</strong>
|
|
Europ. J. Hum. Genet. 21: 1356-1360, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23531866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23531866</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23531866[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=23531866" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ejhg.2013.52" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Bespalova2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bespalova, I. N., Van Camp, G., Bom, S. J. H., Brown, D. J., Cryns, K., DeWan, A. T., Erson, A. E., Flothmann, K., Kunst, H. P. M., Kurnool, P., Sivakumaran, T. A., Cremers, C. W. R. J., Leal, S. M., Burmeister, M., Lesperance, M. M.
|
|
<strong>Mutations in the Wolfram syndrome 1 gene (WFS1) are a common cause of low frequency sensorineural hearing loss.</strong>
|
|
Hum. Molec. Genet. 10: 2501-2508, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709537</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11709537[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=11709537" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/10.22.2501" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Colosimo2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Colosimo, A., Guida, V., Rigoli, L., Di Bella, C., De Luca, A., Briuglia, S., Stuppia, L., Salpietro, D. C., Dallapiccolo, B.
|
|
<strong>Molecular detection of novel WFS1 mutations in patients with Wolfram syndrome by a DHPLC-based assay.</strong>
|
|
Hum. Mutat. 21: 622-629, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12754709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12754709</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12754709" 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.10215" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Cryns2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cryns, K., Pfister, M., Pennings, R. J. E., Bom, S. J. H., Flothmann, K., Caethoven, G., Kremer, H., Schatteman, I., Koln, K. A., Toth, T., Kupka, S., Blin, N., Nurnberg, P., Thiele, H., van de Heyning, P. H., Reardon, W., Stephens, D., Cremers, C. W. R. J., Smith, R. J. H., Van Camp, G.
|
|
<strong>Mutations in the WFS1 gene that cause low-frequency sensorineural hearing loss are small non-inactivating mutations.</strong>
|
|
Hum. Genet. 110: 389-394, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12073007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12073007</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12073007" 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/s00439-002-0719-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Cryns2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cryns, K., Sivakumaran, T. A., Van den Ouweland, J. M. W., Pennings, R. J. E., Cremers, C. W. R. J., Flothmann, K., Young, T.-L., Smith, R. J. H., Lesperance, M. M., Van Camp, G.
|
|
<strong>Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease.</strong>
|
|
Hum. Mutat. 22: 275-287, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12955714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12955714</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12955714" 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.10258" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Domenech2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Domenech, E., Gomez-Zaera, M., Nunes, V.
|
|
<strong>WFS1 mutations in Spanish patients with diabetes mellitus and deafness.</strong>
|
|
Europ. J. Hum. Genet. 10: 421-426, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12107816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12107816</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12107816" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.ejhg.5200823" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Domenech2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Domenech, E., Gomez-Zaera, M., Nunes, V.
|
|
<strong>Study of the WFS1 gene and mitochondrial DNA in Spanish Wolfram syndrome families.</strong>
|
|
Clin. Genet. 65: 463-469, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15151504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15151504</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15151504" 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.1399-0004.2004.00249.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Eiberg2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eiberg, H., Hansen, L., Kjer, B., Hansen, T., Pedersen, O., Bille, M., Rosenberg, T., Tranebjaerg, L.
|
|
<strong>Autosomal dominant optic atrophy associated with hearing impairment and impaired glucose regulation caused by a missense mutation in the WFS1 gene.</strong>
|
|
J. Med. Genet. 43: 435-440, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16648378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16648378</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16648378[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=16648378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2005.034892" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Fonseca2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fonseca, S. G., Fukuma, M., Lipson, K. L., Nguyen, L. X., Allen, J. R., Oka, Y., Urano, F.
|
|
<strong>WFS1 is a novel component of the unfolded protein response and maintains homeostasis of the endoplasmic reticulum in pancreatic beta-cells.</strong>
|
|
J. Biol. Chem. 280: 39609-39615, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16195229/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16195229</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16195229" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M507426200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Fukuoka2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fukuoka, H., Kanda, Y., Ohta, S., Usami, S.
|
|
<strong>Mutations in the WFS1 gene are a frequent cause of autosomal dominant nonsyndromic low-frequency hearing loss in Japanese.</strong>
|
|
J. Hum. Genet. 52: 510-515, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17492394/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17492394</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17492394" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s10038-007-0144-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Gomez-Zaera2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gomez-Zaera, M., Strom, T. M., Rodriguez, B., Estivill, X., Meitinger, T., Nunes, V.
|
|
<strong>Presence of a major WFS1 mutation in Spanish Wolfram syndrome pedigrees.</strong>
|
|
Molec. Genet. Metab. 72: 72-81, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11161832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11161832</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11161832" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/mgme.2000.3107" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Hansen2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hansen, L., Eiberg, H., Barrett, T., Bek, T., Kjaersgaard, P., Tranebjaerg, L., Rosenberg, T.
|
|
<strong>Mutation analysis of the WFS1 gene in seven Danish Wolfram syndrome families; four new mutations identified.</strong>
|
|
Europ. J. Hum. Genet. 13: 1275-1284, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16151413/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16151413</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16151413" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.ejhg.5201491" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Hardy1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hardy, C., Khanim, F., Torres, R., Scott-Brown, M., Seller, A., Poulton, J., Collier, D., Kirk, J., Polymeropoulos, M., Latif, F., Barrett, T.
|
|
<strong>Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1.</strong>
|
|
Am. J. Hum. Genet. 65: 1279-1290, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10521293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10521293</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10521293[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=10521293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302609" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Hildebrand2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hildebrand, M. S., Sorensen, J. L., Jensen, M., Kimberling, W. J., Smith, R. J. H.
|
|
<strong>Autoimmune disease in a DFNA6/14/38 family carrying a novel missense mutation in WFS1.</strong>
|
|
Am. J. Med. Genet. 146A: 2258-2265, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18688868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18688868</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18688868[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=18688868" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.32449" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Hofmann2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hofmann, S., Bauer, M. F.
|
|
<strong>Wolfram syndrome-associated mutations lead to instability and proteasomal degradation of wolframin.</strong>
|
|
FEBS Lett. 580: 4000-4004, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16806192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16806192</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16806192" 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.febslet.2006.06.036" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Hofmann2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hofmann, S., Philbrook, C., Gerbitz, K.-D., Bauer, M. F.
|
|
<strong>Wolfram syndrome: structural and functional analyses of mutant and wild-type wolframin, the WFS1 gene product.</strong>
|
|
Hum. Molec. Genet. 12: 2003-2012, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12913071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12913071</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12913071" 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/ddg214" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Hogewind2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hogewind, B. F. T., Pennings, R. J. E., Hol, F. A., Kunst, H. P. M., Hoefsloot, E. H., Cruysberg, J. R. M., Cremers, C. W. R. J.
|
|
<strong>Autosomal dominant optic neuropathy and sensorineural hearing loss associated with a novel mutation of WFS1.</strong>
|
|
Molec. Vis. 16: 26-35, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20069065/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20069065</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20069065[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=20069065" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Inoue1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Inoue, H., Tanizawa, Y., Wasson, J., Behn, P., Kalidas, K., Bernal-Mizrachi, E., Meuckler, M., Marshall, H., Donis-Keller, H., Crock, P., Rogers, D., Mikuni, M., Kumashiro, H., Higashi, K., Sobue, G., Oka, Y., Permutt, M. A.
|
|
<strong>A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).</strong>
|
|
Nature Genet. 20: 143-148, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9771706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9771706</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9771706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/2441" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Ishihara2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ishihara, H., Takeda, S., Tamura, A., Takahashi, R., Yamaguchi, S., Takei, D., Yamada, T., Inoue, H., Soga, H., Katagiri, H., Tanizawa, Y., Oka, Y.
|
|
<strong>Disruption of the WFS1 gene in mice causes progressive beta-cell loss and impaired stimulus-secretion coupling in insulin secretion.</strong>
|
|
Hum. Molec. Genet. 13: 1159-1170, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15056606/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15056606</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15056606" 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/ddh125" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Khanim2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Khanim, F., Kirk, J., Latif, F., Barrett, T. G.
|
|
<strong>WFS1/Wolframin mutations, Wolfram syndrome, and associated diseases.</strong>
|
|
Hum. Mutat. 17: 357-367, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11317350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11317350</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11317350" 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.1110" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Komatsu2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Komatsu, K., Nakamura, N., Ghadami, M., Matsumoto, N., Kishino, T., Ohta, T., Niikawa, N., Yoshiura, K.
|
|
<strong>Confirmation of genetic homogeneity of nonsyndromic low-frequency sensorineural hearing loss by linkage analysis and a DFNA6/14 mutation in a Japanese family.</strong>
|
|
J. Hum. Genet. 47: 395-399, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12181639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12181639</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12181639" 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/s100380200057" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Lesperance1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lesperance, M. M., Hall, J. W., III, Bess, F. H., Fukushima, K., Jain, P. K., Ploplis, B., San Agustin, T. B., Skarka, H., Smith, R. J. H., Wills, M., Wilcox, E. R.
|
|
<strong>A gene for autosomal dominant nonsyndromic hereditary hearing impairment maps to 4p16.3.</strong>
|
|
Hum. Molec. Genet. 4: 1967-1972, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8595423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8595423</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8595423" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/4.10.1967" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Osman2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Osman, A. A., Saito, M., Makepeace, C., Permutt, M. A., Schlesinger, P., Mueckler, M.
|
|
<strong>Wolframin expression induces novel ion channel activity in endoplasmic reticulum membranes and increases intracellular calcium.</strong>
|
|
J. Biol. Chem. 278: 52755-52762, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14527944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14527944</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14527944" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M310331200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Rendtorff2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rendtorff, N. D., Lodahl, M., Boulahbel, H., Johansen, I. R., Pandya, A., Welch, K. O., Norris, V. W., Arnos, K. S., Bitner-Glindzicz, M., Emery, S. B., Mets, M. B., Fagerheim, T., Eriksson, K., Hansen, L., Bruhn, H., Moller, C., Lindholm, S., Ensgaard, S., Lesperance, M. M., Tranebjaerg, L.
|
|
<strong>Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment.</strong>
|
|
Am. J. Med. Genet. 155A: 1298-1313, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21538838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21538838</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21538838[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=21538838" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/ajmg.a.33970" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Sam2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sam, W., Qin, H., Crawford, B., Yue, D., Yu, S.
|
|
<strong>Homozygosity for a 4-bp deletion in a patient with Wolfram syndrome suggesting possible phenotype and genotype correlation. (Letter)</strong>
|
|
Clin. Genet. 59: 136-138, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11260218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11260218</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11260218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1034/j.1399-0004.2001.590214.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Samuelson1940" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Samuelson, A.
|
|
<strong>Familjart upptradande synnervsatrofi och dovhet.</strong>
|
|
Nord. Med. 6: 769-772, 1940.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Sandhu2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sandhu, M. S., Weedon, M. N., Fawcett, K. A., Wasson, J., Debenham, S. L., Daly, A., Lango, H., Frayling, T. M., Neumann, R. J., Sherva, R., Blech, I., Pharoah, P. D., and 12 others.
|
|
<strong>Common variants in WFS1 confer risk of type 2 diabetes.</strong>
|
|
Nature Genet. 39: 951-953, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17603484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17603484</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17603484" 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/ng2067" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Strom1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Strom, T. M., Hortnagel, K., Hofmann, S., Gekeler, F., Scharfe, C., Rabl, W., Gerbitz, K. D., Meitinger, T.
|
|
<strong>Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein.</strong>
|
|
Hum. Molec. Genet. 7: 2021-2028, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9817917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9817917</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9817917" 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/7.13.2021" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Takeda2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Takeda, K., Inoue, K., Tanizawa, Y., Matsuzaki, Y., Oba, J., Watanabe Y., Shinoda, K., Oka, Y.
|
|
<strong>WFS1 (Wolfram syndrome 1) gene product: predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain.</strong>
|
|
Hum. Molec. Genet. 10: 477-484, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11181571/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11181571</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11181571" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/10.5.477" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Tessa2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tessa, A., Carbone, I., Matteoli, M. C., Bruno, C., Patrono, C., Patera, I. P., De Luca, F., Lorini, R., Santorelli, F. M.
|
|
<strong>Identification of novel WFS1 mutations in Italian children with Wolfram syndrome.</strong>
|
|
Hum. Mutat. 17: 348-349, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11295831/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11295831</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11295831" 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.32" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Valero2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Valero, R., Bannwarth, S., Roman, S., Paquis-Flucklinger, V., Vialettes, B.
|
|
<strong>Autosomal dominant transmission of diabetes and congenital hearing impairment secondary to a missense mutation in the WFS1 gene.</strong>
|
|
Diabet. Med. 25: 657-661, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18544103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18544103</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18544103" 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.1464-5491.2008.02448.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Young2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Young, T.-L., Ives, E., Lynch, E., Person, R., Snook, S., MacLaren, L., Cater, T., Griffin, A., Fernandez, B., Lee, M. K., King, M.-C.
|
|
<strong>Non-syndromic progressive hearing loss DFNA38 is caused by heterozygous missense mutation in the Wolfram syndrome gene WFS1.</strong>
|
|
Hum. Molec. Genet. 10: 2509-2514, 2001. Note: Erratum: Hum. Molec. Genet. 10: 3111 only, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11709538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11709538</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11709538" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/10.22.2509" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Zalloua2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zalloua, P. A., Azar, S. T., Delepine, M., Makhoul, N. J., Blanc, H., Sanyoura, M., Lavergne, A., Stankov, K., Lemainque, A., Baz, P., Julier, C.
|
|
<strong>WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon.</strong>
|
|
Hum. Molec. Genet. 17: 4012-4021, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18806274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18806274</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18806274" 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/ddn304" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Zatyka2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zatyka, M., Ricketts, C., Xavier, G. S., Minton, J., Fenton, S., Hofmann-Thiel, S., Rutter, G. A., Barrett, T. G.
|
|
<strong>Sodium-potassium ATPase beta-1 subunit is a molecular partner of Wolframin, an endoplasmic reticulum protein involved in ER stress.</strong>
|
|
Hum. Molec. Genet. 17: 190-200, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17947299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17947299</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17947299[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=17947299" 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/ddm296" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Marla J. F. O'Neill - updated : 1/14/2014
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Marla J. F. O'Neill - updated : 10/19/2011<br>Marla J. F. O'Neill - updated : 9/22/2011<br>Marla J. F. O'Neill - updated : 6/1/2009<br>Matthew B. Gross - updated : 5/13/2009<br>Patricia A. Hartz - updated : 5/4/2009<br>Cassandra L. Kniffin - updated : 1/5/2009<br>Marla J. F. O'Neill - updated : 9/25/2007<br>George E. Tiller - updated : 9/6/2006<br>Marla J. F. O'Neill - updated : 6/16/2006<br>Cassandra L. Kniffin - updated : 3/2/2006<br>George E. Tiller - updated : 6/3/2005<br>Victor A. McKusick - updated : 6/23/2004<br>Victor A. McKusick - updated : 10/23/2003<br>Victor A. McKusick - updated : 7/11/2003<br>Michael B. Petersen - updated : 5/15/2003<br>Victor A. McKusick - updated : 11/11/2002<br>Victor A. McKusick - updated : 8/6/2002<br>Victor A. McKusick - updated : 6/7/2002<br>George E. Tiller - updated : 5/7/2002<br>George E. Tiller - updated : 12/13/2001<br>Ada Hamosh - reorganized : 8/15/2001
|
|
</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 : 8/14/2001
|
|
</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 : 03/06/2024
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 09/04/2020<br>carol : 09/03/2020<br>carol : 09/02/2020<br>carol : 04/24/2018<br>alopez : 07/27/2015<br>mcolton : 7/21/2015<br>carol : 1/14/2014<br>carol : 9/16/2013<br>carol : 8/5/2013<br>carol : 8/5/2013<br>alopez : 4/25/2013<br>terry : 6/20/2012<br>carol : 2/13/2012<br>terry : 10/26/2011<br>terry : 10/19/2011<br>carol : 10/19/2011<br>carol : 9/23/2011<br>terry : 9/22/2011<br>alopez : 6/4/2010<br>wwang : 2/25/2010<br>wwang : 6/2/2009<br>terry : 6/1/2009<br>mgross : 5/13/2009<br>terry : 5/4/2009<br>wwang : 1/8/2009<br>ckniffin : 1/5/2009<br>terry : 12/2/2008<br>alopez : 11/12/2007<br>alopez : 9/25/2007<br>alopez : 9/6/2006<br>wwang : 6/16/2006<br>wwang : 3/2/2006<br>alopez : 6/3/2005<br>terry : 3/3/2005<br>tkritzer : 6/28/2004<br>terry : 6/23/2004<br>terry : 3/24/2004<br>carol : 3/5/2004<br>cwells : 10/23/2003<br>terry : 10/23/2003<br>cwells : 7/16/2003<br>terry : 7/11/2003<br>cwells : 5/15/2003<br>alopez : 11/13/2002<br>terry : 11/11/2002<br>carol : 8/8/2002<br>tkritzer : 8/7/2002<br>terry : 8/6/2002<br>alopez : 6/12/2002<br>terry : 6/7/2002<br>alopez : 5/7/2002<br>alopez : 5/7/2002<br>cwells : 1/11/2002<br>cwells : 12/13/2001<br>carol : 8/22/2001<br>carol : 8/21/2001<br>carol : 8/15/2001<br>carol : 8/15/2001
|
|
</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> 606201
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
WOLFRAMIN ER TRANSMEMBRANE GLYCOPROTEIN; WFS1
|
|
|
|
</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">
|
|
WOLFRAMIN
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: WFS1</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 4p16.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 4:6,269,850-6,303,265 </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="5">
|
|
<span class="mim-font">
|
|
4p16.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Cataract 41
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
116400
|
|
</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">
|
|
{Diabetes mellitus, noninsulin-dependent, association with}
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
125853
|
|
</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 dominant 6/14/38
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
600965
|
|
</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">
|
|
Wolfram syndrome 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
222300
|
|
</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">
|
|
Wolfram-like syndrome, autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
614296
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Strom et al. (1998) screened 4 candidate genes in a refined critical linkage interval for Wolfram syndrome (WFS1; 222300) on chromosome 4p16. One of these genes, WFS1, which they called 'wolframin,' codes for a predicted 890-amino acid transmembrane protein with a calculated molecular mass of about 100 kD. WFS1 was predicted to have 9 central transmembrane domains, with an extracytoplasmic N terminus and an intracytoplasmic C terminus. Human WFS1 shares 87% amino acid identity with its mouse homolog. Northern blot analysis detected a 3.6-kb transcript in all human tissues examined. Expression was strong in heart, intermediate in brain, placenta, lung, and pancreas, and weak in liver, skeletal muscle, and kidney. </p><p>Independently, Inoue et al. (1998) positionally cloned the WFS1 gene. They obtained the full-length cDNA by screening an infant brain cDNA library, followed by 5-prime RACE. The WFS1 hydrophobicity curve suggested the presence of approximately 10 transmembrane segments in WFS1. Northern blot analysis detected a major transcript of 3.7 kb in all human tissues examined, including pancreas. Northern blot analysis of total RNA showed high expression of WFS1 in pancreatic islets compared with exocrine pancreas. </p><p>Hofmann et al. (2003) reported that wolframin is ubiquitously expressed, with highest levels in brain, pancreas, heart, and insulinoma beta-cell lines. Wolframin assembled into higher molecular weight complexes of 400 kD in the membrane, and N-glycosylation was essential for its biogenesis and stability. </p><p>By Western blot, Berry et al. (2013) demonstrated expression of Wfs1 in whole mouse eye at embryonic day 18.5 (E18.5) and in whole lens tissue extract at postnatal days 3 and 21. Immunocytochemistry demonstrated high-level expression of Wfs1 in the developing mouse lens at E18.5, but not at E12.5. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Inoue et al. (1998) found that the WFS1 gene contains 8 exons, spanning 33.4 kb of genomic DNA. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By genomic sequence analysis, Strom et al. (1998) mapped the WFS1 gene to chromosome 4p16. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using biochemical methods, Takeda et al. (2001) showed that the WFS1 protein is an integral, endoglycosidase H-sensitive membrane glycoprotein that localizes primarily in the endoplasmic reticulum (ER). Immunofluorescence staining of overexpressed WFS1 in transiently transfected COS-7 cells showed a characteristic reticular pattern over the cytoplasm and overlapped with ER marker staining. In rat brain, at both the protein and mRNA level, WFS1 was present predominantly in selected neurons in the hippocampus CA1, amygdaloid areas, olfactory tubercle, and superficial layer of the allocortex. </p><p>Osman et al. (2003) found that human WFS1 expressed in Xenopus oocytes localized to the ER. Planar oocyte lipid bilayers containing WFS1 showed a large cation-selective channel activity that was blocked by Mg(2+) or Ca(2+). Fused bilayers containing WFS1 showed an elevated slope conductance following activation by inositol 1,4,5-triphosphate. Osman et al. (2003) proposed that WFS1 functions as an ER calcium channel or as a regulator of ER calcium channel activity. </p><p>Using real-time PCR, Fonseca et al. (2005) found that Wfs1 was induced by ER stress in mouse fibroblasts and that its expression was controlled by Ire1-alpha (ERN1; 604033) and Perk (EIF2AK3; 604032), which are involved in the unfolded protein response. Expression of Wfs1 was upregulated in mouse islets during glucose-induced insulin secretion, and knockdown of Wfs1 in mouse beta cells resulted in ER stress and cell dysfunction. Fonseca et al. (2005) hypothesized that Wolfram syndrome involves chronic ER stress in pancreatic beta cells. </p><p>Using yeast 2-hybrid analysis, Zatyka et al. (2008) found that the C-terminal domain of WFS1, which is positioned in the ER lumen, bound the C-terminal domain of the ER-localized Na+/K+ ATPase beta-1 subunit (ATP1B1; 182330). The interaction was confirmed by reciprocal coimmunoprecipitation analysis of proteins expressed in transfected COS-7 cells and endogenous proteins in human and mouse cell lines. Wolfram syndrome patient fibroblasts with 2 different WFS1 mutations showed reduced ATP1B1 levels. Conversely, knockdown of Atp1b1 expression in a mouse insulinoma cell line led to reduced Wfs1 expression. Zatyka et al. (2008) concluded that interaction with WFS1 may be important for ATP1B1 maturation in the ER and that loss of this interaction may contribute to the pathology seen in Wolfram syndrome. </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>Wolfram Syndrome 1</em></strong></p><p>
|
|
Strom et al. (1998) identified loss-of-function mutations in both alleles of the WFS1 gene in patients with Wolfram syndrome-1 (WFS1; 222300). Homozygous mutations were found in 5 families; compound heterozygosity was found in 3 other families. In a ninth family, only a heterozygous stop mutation was found. No mutations in either allele were detected in 3 other families. One of the families was reportedly consanguineous but no mutations were detected in that family. Mutations in exon 1, which was not included in the mutation screen, intronic mutations including deletions, or mutations in the regulatory flanking regions of the gene could be pathogenic in these families. </p><p>Hardy et al. (1999) performed direct DNA sequencing to screen the entire coding region of the WFS1 gene in 30 patients from 19 British kindreds with Wolfram syndrome. DNA was also screened for structural rearrangements (deletions and duplications) and point mutations in mtDNA. No pathogenic mtDNA mutations were found in this cohort. The authors identified 24 mutations in the WFS1 gene: 8 nonsense mutations, 8 missense mutations, 3 in-frame deletions, 1 in-frame insertion, and 4 frameshift mutations. Of these, 23 were novel mutations, and most occurred in exon 8. Most patients were compound heterozygotes for 2 mutations, and there was no common founder mutation. The data were also analyzed for genotype-phenotype relationships. Although some interesting cases were noted, consideration of the small sample size and frequency of each mutation indicated no clear-cut correlations between any of the observed mutations and disease severity. There were no obvious mutation hotspots or clusters. </p><p>Khanim et al. (2001) stated that mutation analysis of the WFS1 gene had identified mutations in 90% of patients with Wolfram syndrome. Most were compound heterozygotes with private mutations distributed throughout the gene with no obvious hotspots. </p><p>Colosimo et al. (2003) identified 19 different mutations in the WFS1 gene in a study of 19 Italian patients with Wolfram syndrome. Mutations were found in 18 of the 19 patients (95%). All of the mutations except 1 were novel, were preferentially located in WFS1 exon 8, and included deletions, insertions, duplications, and nonsense and missense changes. In particular, a 16-bp deletion in WFS1 codon 454 (606201.0019) was detected in 5 different unrelated nuclear families, being the most prevalent alteration in these Italian patients. </p><p>In a review of the mutational spectrum of the WFS1 gene, Cryns et al. (2003) pointed out that mutations associated with Wolfram syndrome are spread over the entire coding region and are typically inactivating, suggesting that a loss of function causes the disease phenotype. In contrast, only noninactivating mutations have been found in DFNA6/14 families, and these mutations are mainly located in the C-terminal protein domain. </p><p>In a study of 6 Spanish families with a total of 7 Wolfram syndrome patients, Domenech et al. (2004) identified 3 previously undescribed mutations in the WFS1 gene as well as the duplication 409dup16 (606201.0013), previously reported as 425ins16 (Gomez-Zaera et al., 2001). </p><p>Hansen et al. (2005) identified mutations in the WFS1 gene in 8 affected members of 7 Danish families with Wolfram syndrome. Four of the mutations were novel. Mutations were identified in 11 of 14 disease chromosomes; in 3 families, only 1 mutation was found. </p><p>Zalloua et al. (2008) performed family-based linkage analysis followed by systematic screening of WFS1 exons in Lebanese juvenile-onset insulin-dependent diabetes (222100) probands and found homozygous or compound heterozygous WFS1 mutations in 22 (5.5%) of the 399 probands, of whom 17 were diagnosed with WFS and 5 with nonsyndromic nonautoimmune diabetes mellitus. Overall, 38 probands and affected family members were homozygous or compound heterozygous for WFS1 mutations, 11 (29%) of whom were diagnosed with nonsyndromic DM; all of the latter patients carried a complex WFS1 mutation (606201.0024), which the authors designated WFS1(LIB) and which resulted in the delayed onset or absence of extrapancreatic features of WFS. In addition, there were 2 patients with an initial diagnosis of nonsyndromic DM that was revised to WFS when they developed optic atrophy during the course of the study; Zalloua et al. (2008) noted that longer follow-up of the WFS1-mutated nonsyndromic DM patients or a specific study of adult patient populations would be needed to determine whether a subset of the WFS1(LIB) patients are exempted from extrapancreatic manifestations during their lifetime. </p><p><strong><em>Pathophysiology of WFS1 Mutations in Wolfram Syndrome</em></strong></p><p>
|
|
In a patient carrying both a nonsense (frameshift) and a missense mutation, Hofmann et al. (2003) detected mRNA levels half that of controls; sequencing confirmed that these transcripts were exclusively derived from the missense allele. Transfection experiments with the missense transcript revealed a markedly reduced steady-state level of wolframin and a strongly reduced half-life. Hofmann et al. (2003) concluded that the pathophysiology in Wolfram syndrome in the presence of a missense mutation is likely that of reduced protein dosage rather than dysfunction of the mutant protein. </p><p>By analyzing WFS1 patient cells and COS-7 cells expressing 4 missense and 2 truncating mutations in WFS1, Hofmann and Bauer (2006) found that all mutations led to drastically reduced steady-state levels of WFS1 protein. Mutant proteins were highly unstable and were removed by proteasomal degradation. Hofmann and Bauer (2006) concluded that WFS1 mutations cause loss of function by cellular depletion of WFS1. </p><p><strong><em>Autosomal Dominant Nonsyndromic Sensorineural Deafness</em></strong></p><p>
|
|
Bespalova et al. (2001) defined a subset of nonsyndromic sensorineural hearing loss affecting low frequencies without profound deafness (600965) in which all individuals studied had WFS1 mutations (e.g., 606201.0015). This subset included families that had been linked to loci designated DFNA6 and DFNA14. Bespalova et al. (2001) concluded that mutations in the WFS1 gene are a common cause of sensorineural hearing loss. Additionally, an autosomal dominant sensorineural hearing loss designated DFNA38 was shown to be caused by mutation in the WFS1 gene (606201.0014). </p><p>Cryns et al. (2002) stated that only 2 of the more than 70 loci identified as associated with hereditary hearing impairment are associated with an auditory phenotype that predominantly affects the low frequencies: DFNA1 (124900) and DFNA6/14 (600965). Cryns et al. (2002) did mutation screening of the WFS1 gene in 8 autosomal dominant families and 12 sporadic cases in which affected persons had low-frequency sensorineural hearing impairment. They identified 7 missense mutations and a single amino acid deletion affecting conserved amino acids in 6 families and 1 sporadic case, indicating that mutations in WFS1 are a major cause of inherited low-frequency hearing impairment. Among the 10 WFS1 mutations reported in low-frequency sensorineural hearing impairment, none was expected to lead to premature protein termination, and 9 clustered in the C-terminal protein domain. In contrast, 64% of the Wolfram syndrome mutations are inactivating. The results indicated that only noninactivating mutations in WFS1 are responsible for nonsyndromic low-frequency hearing impairment. </p><p>Fukuoka et al. (2007) analyzed the WFS1 gene in 206 Japanese autosomal dominant and 64 autosomal recessive (sporadic) nonsyndromic hearing loss probands with varying severities of hearing loss and identified 2 different missense mutations in 3 unrelated families (see 606201.0014 and 606201.0020, respectively). All of the mutation-positive patients had dominantly inherited low-frequency sensorineural hearing loss. Because both mutations had previously been identified in patients of European ancestry, Fukuoka et al. (2007) suggested that the sites are likely to be mutation hotspots. </p><p><strong><em>Autosomal Dominant Wolfram-like Syndrome</em></strong></p><p>
|
|
Domenech et al. (2002) screened the WFS1 gene in 48 patients with autosomal recessive deafness, 38 patients with type 2 diabetes mellitus (T2D; 125853), and 23 patients with both deafness and T2D. In 3 unrelated patients who had both deafness and diabetes, they identified 3 different heterozygous missense mutations, which were located in the intracytoplasmic domain of the protein and were not detected in 49 healthy controls. Domenech et al. (2002) stated that the lack of knowledge about the function of WFS1 made it difficult to explain the possible contribution of these mutations to the diseases. One of the mutations, V871M, was also found in a patient who had only deafness and was present in her deaf sister, but was detected in her unaffected father. (The V871M variant had previously been detected by Young et al., 2001 in a family with autosomal dominant deafness, but did not segregate with disease in that family; see 606201.0014.) </p><p>In a 3-generation Danish family segregating an autosomal dominant Wolfram-like syndrome (WFSL; 614296) in which affected individuals had deafness, optic atrophy, and impaired glucose regulation mapping to chromosome 4p16.3, Eiberg et al. (2006) analyzed the candidate gene WFS1 and identified a missense mutation (E864K; 606201.0020) in affected individuals. The mutation was not found in unaffected family members or in 2 family members who had only isolated congenital hearing impairment. </p><p>In a 60-year-old French man with congenital hearing impairment and T2D and his 81-year-old mother with deafness, diabetes, and optic atrophy, both of whom were known to be negative for the common mtDNA mutations associated with the maternally inherited diabetes-deafness syndrome (MIDD; 520000), Valero et al. (2008) identified heterozygosity for the E864K mutation in the WFS1 gene. </p><p>In affected members of a Dutch family with deafness and optic neuropathy in whom screening of the OPA1 gene (605290) and mtDNA screening for the 3 most frequent Leber optic atrophy (535000) mutations were both negative, Hogewind et al. (2010) identified heterozygosity for a missense mutation in the WFS1 gene (K836N; 606201.0027). </p><p>Rendtorff et al. (2011) analyzed the WFS1 gene in 15 probands with deafness and optic atrophy who were known to be negative for mutation in the OPA1 and TIMM8A (300356) genes, and identified heterozygosity for the same missense mutation in the WFS1 gene (A684V; 606201.0028) in 6 probands. Two additional probands were heterozygous for 2 different WFS1 missense mutations (see, e.g., 606201.0031). In 7 of the 8 mutation-positive families, there were spouses with isolated sensorineural hearing loss (SNHL); analysis of the GJB2 gene (121011) revealed that 3 of the probands who were heterozygous for mutation in WFS1 also carried a known SNHL-related mutation in the GJB2 gene (121011.0001 or 121011.0005), inherited from a deaf parent who did not have optic atrophy. </p><p><strong><em>Cataract 41</em></strong></p><p>
|
|
In an affected member of a 4-generation family of Irish descent segregating autosomal dominant congenital nuclear cataract mapping to chromosome 4p16.1 (CTRCT41; 116400), Berry et al. (2013) performed exome sequencing and identified heterozygosity for a missense mutation in the WFS1 gene (606201.0032). Direct genomic sequencing confirmed that the mutation cosegregated completely with disease in the family. Screening of the WFS1 gene in a panel of 50 unrelated individuals with autosomal dominant cataract did not reveal any other mutations. </p><p><strong><em>Association with Type 2 Diabetes Mellitus</em></strong></p><p>
|
|
Sandhu et al. (2007) conducted a gene-centric association study for type 2 diabetes mellitus (T2D; 125853) in multiple large cohorts and identified 2 SNPs located in the WFS1 gene, rs10010131 (606201.0021) and rs6446482 (602201.0022), that were strongly associated with diabetes risk (P = 1.4 x 10(-7) and P = 3.4 x 10(-7), respectively, in the pooled study set). The risk allele was the major allele for both SNPs, with a frequency of 60% for both. The authors noted that both are intronic, with no obvious evidence for biologic function. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Ishihara et al. (2004) disrupted the wfs1 gene in mice. The mutant mice developed glucose intolerance or overt diabetes due to insufficient insulin (see 176730) secretion in vivo. Islets isolated from mutant mice exhibited decreased insulin secretion in response to glucose. The defective insulin secretion was accompanied by reduced cellular calcium responses to the secretagogue. Immunohistochemical analyses demonstrated progressive beta-cell loss in mutant mice, while alpha cells, which barely express WFS1 protein, were preserved. Furthermore, isolated islets from mutant mice exhibited increased apoptosis, at high concentration of glucose or with exposure to endoplasmic reticulum stress inducers. The authors suggested that WFS1 protein may play an important role in both stimulus-secretion coupling for insulin exocytosis and maintenance of beta-cell mass. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>32 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, 2-BP DEL, 2812TC
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs863224268,
|
|
|
|
|
|
|
|
ClinVar: RCV000199613, RCV001668365, RCV005042421
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected sibs with Wolfram syndrome (WFS1; 222300) in a consanguineous Japanese family, Inoue et al. (1998) found a TC deletion at position 2812 in the WFS1 sequence. The deletion was predicted to cause a frameshift at codon 882; they referred to the mutation as del882fs/ter937. The normal stop codon at 891 was absent and a new downstream termination codon had been introduced. The predicted protein contained 937 amino acids, 47 more than the normal protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, 15-BP DEL, NT1685
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs781262017,
|
|
|
|
|
|
gnomAD: rs781262017,
|
|
|
|
|
|
ClinVar: RCV001941578, RCV002274237, RCV002507696, RCV003336476
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a consanguineous Japanese family segregating Wolfram syndrome (WFS1; 222300), Inoue et al. (1998) demonstrated that 4 affected sibs were homozygous for a 15-bp deletion in the WFS1 gene resulting in deletion of 5 amino acids, tyr-val-tyr-leu-leu, beginning with residue 508. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, PRO724LEU ({dbSNP rs28937890})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28937890,
|
|
|
|
|
|
gnomAD: rs28937890,
|
|
|
|
|
|
ClinVar: RCV000004767, RCV000756934
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese family segregating Wolfram syndrome (WFS1; 222300), Inoue et al. (1998) demonstrated that affected members were homozygous for a 2341C-T transition resulting in a pro724-to-leu (P724L) amino acid substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, GLY695VAL ({dbSNP rs28937891})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28937891,
|
|
|
|
|
|
gnomAD: rs28937891,
|
|
|
|
|
|
ClinVar: RCV000004768, RCV005031390, RCV005089167
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a European family, Inoue et al. (1998) demonstrated that 3 sibs with Wolfram syndrome (WFS1; 222300) were compound heterozygous for a 2254G-T transversion resulting in a gly695-to-val (G695V) amino acid substitution (inherited from the father); and a 2114G-A transition resulting in a trp648-to-ter (W648X; 606201.0005) termination of the protein, predicted to lack 242 amino acids of the C terminus (inherited from the mother). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, TRP648TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104893879,
|
|
|
|
|
|
gnomAD: rs104893879,
|
|
|
|
|
|
ClinVar: RCV000004769, RCV003114176
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the trp648-to-ter (W648X) mutation in the WFS1 gene that was found in compound heterozygous state in sibs with Wolfram syndrome (WFS1; 222300) by Inoue et al. (1998), see 606201.0004. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, PRO504LEU ({dbSNP rs28937892})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28937892,
|
|
|
|
|
|
gnomAD: rs28937892,
|
|
|
|
|
|
ClinVar: RCV000004770, RCV001387727, RCV002243622, RCV002496259, RCV004737135
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Australian family, Inoue et al. (1998) found apparent homozygosity for a 1681C-T transition (pro504 to leu; P504L) of the WFS1 gene in 3 sibs with Wolfram syndrome (WFS1; 222300). The father was shown to be heterozygous for 1681C-T, but the mother was homozygous 1681C. An unaffected child appeared to be homozygous for 1681C. The mother's chromosome 4, inherited by each child, was thought to harbor a microscopic deletion for WFS1, making the affected offspring hemizygous for the P504L mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, 7-BP INS, NT1610
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs727503745,
|
|
|
|
|
|
|
|
ClinVar: RCV000152660, RCV002273965
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 10-year-old Saudi Arabian child with Wolfram syndrome (WFS1; 222300), born to first-cousin parents, Inoue et al. (1998) found homozygosity for a 7-bp repeat insertion at nucleotide 1610 (CTGAAGG), resulting in a predicted frameshift and premature termination of the protein at codon 544. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, 9-BP DEL, NT1380
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1578609780,
|
|
|
|
|
|
|
|
ClinVar: RCV000004772
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Strom et al. (1998) found a 9-bp deletion in exon 8 of the WFS1 gene in a 22-year-old female with Wolfram syndrome (WFS1; 222300). The deletion began at nucleotide 1380, counting from the first base of the start codon, and was present in homozygous state. The patient had onset of diabetes mellitus and diabetes insipidus at 6 years of age and also had progressive optic atrophy, abnormal audiogram, renal tract abnormalities, retarded sexual maturation, ataxia and nystagmus, and depression. A sister with the same mutation had onset of diabetes mellitus at 4 years of age, and at the age of 11 years had renal tract abnormalities as the only additional feature. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, 460, G-A, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1191510461,
|
|
|
|
|
|
gnomAD: rs1191510461,
|
|
|
|
|
|
ClinVar: RCV000004773, RCV001588798
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a brother and sister with Wolfram syndrome (WFS1; 222300), Strom et al. (1998) found homozygosity for a splicing mutation in the WFS1 gene: 460+1G-A in the 5-prime splice signal of exon 4. In the brother and sister, diabetes mellitus began at ages 10 and 9 years, progressive optic atrophy at 14 and 12 years, abnormal audiogram at 13 and 17 years, and diabetes insipidus at 15 and 15 years, respectively. Renal tract abnormalities were present only in the brother, who at the age of 17 years showed retarded sexual maturation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, GLN226TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104893880,
|
|
|
|
|
|
gnomAD: rs104893880,
|
|
|
|
|
|
ClinVar: RCV000004774
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 25-year-old female patient with Wolfram syndrome (WFS1; 222300), Strom et al. (1998) found compound heterozygosity for 2 nonsense mutations in the WFS1 gene: gln226 to ter (Q226X) and gln819 to ter (Q819X; 606201.0011). These mutations were located in exons 6 and 8, respectively. The patient had onset of diabetes mellitus and diabetes insipidus at 7 years of age; progressive optic atrophy began at 9 years, abnormal audiogram at 22 years, and renal tract abnormalities at 24 years. She also had ataxia and nystagmus. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, GLN819TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104893881,
|
|
|
|
|
|
gnomAD: rs104893881,
|
|
|
|
|
|
ClinVar: RCV000004775
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the gln819-to-ter (Q819X) mutation in the WFS1 gene that was found in compound heterozygous state in a patient with Wolfram syndrome (WFS1; 222300) by Strom et al. (1998), see 606201.0010. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, 4-BP DEL, NT2648
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs797045076,
|
|
|
|
|
|
|
|
ClinVar: RCV000191146, RCV000200365, RCV001536011
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Hardy et al. (1999) and Sam et al. (2001) described Wolfram syndrome (WFS1; 222300) with a distinctive phenotype, namely, central respiratory failure: the patients were homozygous for a 4-bp (TCTT) deletion at position 2648-2651 in exon 8 of the WFS1 gene. The deletion caused loss of codon 883 and a frameshift, producing a 949-amino acid WFS1 protein, which was 59 amino acids longer than normal. The mutation changed the last 7 amino acids of the C terminus of the protein, leaving the transmembrane domains intact. In the patient with the 4-bp deletion reported by Hardy et al. (1999), there was severe brainstem atrophy and central respiratory failure requiring tracheostomy. Her affected sister had died at age 28 from brainstem atrophy and central respiratory failure. Five patients (from 3 families) who were heterozygous for the 4-bp deletion did not have respiratory failure. The 33-year-old patient reported by Sam et al. (2001) was diagnosed as having diabetes mellitus, a neurogenic bladder, and bilateral optic atrophy at the age of 10, 13, and 15, respectively. Audiometry was normal, and there was no evidence of diabetes insipidus. After an episode of respiratory arrest at age 32, she required intubation, ventilation, and subsequently, tracheostomy. MRI scan showed marked brainstem atrophy. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, 16-BP DUP, NT409
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1362648752,
|
|
|
|
|
|
gnomAD: rs1362648752,
|
|
|
|
|
|
ClinVar: RCV000004777, RCV000499974, RCV000778736, RCV001385126, RCV001542530, RCV004814825
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Gomez-Zaera et al. (2001) studied 22 Wolfram syndrome (WFS1; 222300) patients from 16 Spanish families for mutations in the WFS1 coding region by SSCP analysis and direct sequencing. Fifty percent of the pedigrees were found to have a single mutation, 67% in homozygosity and 33% in compound heterozygosity. The authors stated that the mutation is a 16-bp insertion in exon 4 at nucleotide 425 and is predicted to produce an aberrant protein; assuming that no splicing alterations occur, translation will follow until residue 251, where a stop codon is created. The high incidence of this mutation in Spanish families may be explained by a founder effect. </p><p>In 4 patients from 3 Spanish families with Wolfram syndrome, Domenech et al. (2004) identified the 425ins16 mutation, which they referred to as a 16-bp duplication (409dup16). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 DEAFNESS, AUTOSOMAL DOMINANT 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, ALA716THR ({dbSNP rs28937893})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28937893,
|
|
|
|
|
|
gnomAD: rs28937893,
|
|
|
|
|
|
ClinVar: RCV000004778, RCV000522349, RCV000599627
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Young et al. (2001) described a 6-generation Canadian family with dominantly inherited progressive hearing loss (DFNA6; 600965), in which affected individuals were heterozygous for a 2146G-A transition in WFS1. The mutation resulted in an ala716-to-thr (A716T) substitution. Affected individuals lacked additional phenotypic features seen in Wolfram syndrome, with the exception of a child who was homozygous for the mutation and also manifested diabetes mellitus by the age of 3 years. </p><p>In 2 affected members of a 3-generation Japanese family segregating autosomal dominant nonsyndromic low-frequency sensorineural hearing loss, Fukuoka et al. (2007) identified heterozygosity for the A716T mutation in the WFS1 gene. The mutation was not found in 3 unaffected family members or in 86 controls. Because the same mutation was previously found in a family of European ancestry, the authors suggested that this might represent a mutation hotspot. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 DEAFNESS, AUTOSOMAL DOMINANT 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, LEU829PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104893883,
|
|
|
|
|
|
|
|
ClinVar: RCV000004779, RCV000726781, RCV001267554, RCV003155015, RCV005041982
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Bespalova et al. (2001) described a 3-generation American family with low-frequency sensorineural hearing loss (DFNA6; 600965). Affected individuals were heterozygous for a T2656C transition in the WFS1 gene, resulting in a leu829-to-pro (L829P) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 DEAFNESS, AUTOSOMAL DOMINANT 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, THR699MET ({dbSNP rs28937894})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28937894,
|
|
|
|
|
|
|
|
ClinVar: RCV000004780, RCV000238945, RCV001851653
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Bespalova et al. (2001) and Cryns et al. (2002) described patients with low-frequency sensorineural hearing loss (DFNA6; 600965) due to a 2096C-T nucleotide change in exon 8 of the WFS1 gene, predicting a thr699-to-met (T699M) protein change. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 DEAFNESS, AUTOSOMAL DOMINANT 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, GLY831ASP ({dbSNP rs28937895})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28937895,
|
|
|
|
|
|
gnomAD: rs28937895,
|
|
|
|
|
|
ClinVar: RCV000004781, RCV000521055
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Bespalova et al. (2001) and Cryns et al. (2002) described patients with low-frequency sensorineural hearing loss (DFNA6; 600965) due to a 2492G-A transition in exon 8 of the WFS1 gene, predicting a gly831-to-asp (G831D) amino acid change. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 DEAFNESS, AUTOSOMAL DOMINANT 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, LYS634THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104893882,
|
|
|
|
|
|
gnomAD: rs104893882,
|
|
|
|
|
|
ClinVar: RCV000004782
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese family in which 20 members had nonsyndromic low-frequency sensorineural hearing loss (DFNA6; 600965), Komatsu et al. (2002) demonstrated linkage to chromosome 4p16 and found a novel missense mutation, lys634 to thr (K634T), in the WFS1 gene. The mutation was located in the hydrophobic, extracytoplasmic, juxta-transmembrane region of the WFS1 protein. The mutation site was thought to be related to the milder phenotype (lacking tinnitus) in the Japanese family compared with the findings in 6 previously reported patients with WFS1 mutations (Lesperance et al., 1995; Strom et al., 1998). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, 16-BP DEL, NT1362
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1730884546,
|
|
|
|
|
|
|
|
ClinVar: RCV001172534, RCV001873597, RCV002274141
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In Wolfram syndrome (WFS1; 222300) patients from 5 different unrelated Italian families, Colosimo et al. (2003) found a 16-bp deletion in the WFS1 gene that removed nucleotides 1362 to 1377, causing a frameshift with premature termination at codon 454. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 WOLFRAM-LIKE SYNDROME, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
DEAFNESS, AUTOSOMAL DOMINANT 6, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, GLU864LYS ({dbSNP rs74315205})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs74315205,
|
|
|
|
|
|
|
|
ClinVar: RCV000004784, RCV000020637, RCV000523215, RCV000599631, RCV001528145, RCV001544536, RCV004794324, RCV004797754, RCV004814826
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a 3-generation Danish family with an autosomal dominant Wolfram-like syndrome (WFSL; 614296), Eiberg et al. (2006) identified heterozygosity for a 2590G-A transition in exon 8 of the WFS1 gene, resulting in a glu864-to-lys (E864K) substitution. Affected individuals had optic atrophy, progressive hearing impairment, and impaired glucose regulation. The mutation was not found in unaffected family members, nor in 2 family members with isolated congenital hearing impairment. </p><p>In 7 affected members from 2 unrelated Japanese families segregating autosomal dominant nonsyndromic low-frequency sensorineural hearing loss (DFNA6; 600965), Fukuoka et al. (2007) identified heterozygosity for the E864K mutation in the WFS1 gene. The mutation was not found in 3 unaffected family members or in 86 controls. Because the same mutation was previously found in a family of European ancestry, the authors suggested that this might represent a mutation hotspot. </p><p>In a 60-year-old French man with congenital hearing impairment and noninsulin-dependent diabetes and his 81-year-old mother with deafness, diabetes, and optic atrophy, Valero et al. (2008) identified heterozygosity for the E864K mutation in the WFS1 gene. The mutation was not found in 100 French controls. The proband, who did not have optic atrophy or any other manifestations of Wolfram syndrome, also carried a 683G-A transition in exon 6 of WFS1, resulting in an arg228-to-gln (R228Q; 606201.0026) substitution at a conserved residue that was not found in controls. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 TYPE 2 DIABETES MELLITUS, ASSOCIATION WITH</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, ({dbSNP rs10010131})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs10010131, rs6446482,
|
|
|
|
|
|
gnomAD: rs10010131, rs6446482,
|
|
|
|
|
|
ClinVar: RCV000004785, RCV000038664, RCV000273205, RCV000325882, RCV001513863, RCV002225069
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an association study for type 2 diabetes (T2D; 125853) involving single-nucleotide polymorphisms (SNPs) in genes with roles in pancreatic beta-cell function, Sandhu et al. (2007) identified association of 2 SNPs in the WFS1 gene, rs10010131 and rs6446482 (606201.0022), with diabetes risk. Analysis of a pooled study set of 9,533 cases and 11,389 controls achieved a P value of 1.4 x 10(-7) for rs10010131 and a P value of 3.4 x 10(-7) for rs6446482. Both of these SNPs are intronic, with no obvious evidence for biologic function. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 TYPE 2 DIABETES MELLITUS, ASSOCIATION WITH</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, ({dbSNP rs6446482})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs6446482,
|
|
|
|
|
|
gnomAD: rs6446482,
|
|
|
|
|
|
ClinVar: RCV000004786, RCV000830171, RCV000987406, RCV001255180, RCV001777131
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the rs6446482 in the WFS1 gene that was found in an association study for type 2 diabetes mellitus (T2D; 125853) by Sandhu et al. (2007), see 606201.0021. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 DEAFNESS, AUTOSOMAL DOMINANT 6</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, ARG859GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121912618,
|
|
|
|
|
|
gnomAD: rs121912618,
|
|
|
|
|
|
ClinVar: RCV000004787, RCV000275899, RCV000480362, RCV002490313, RCV004532289, RCV004814827
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 6 affected members of a family with autosomal dominant sensorineural deafness (DFNA6; 600965), Hildebrand et al. (2008) identified a heterozygous 2576G-A transition in exon 8 of the WFS1 gene, resulting in an arg859-to-gln (R859Q) substitution in the C-terminal domain. Two affected females had concurrent Crohn disease (see 266600) and Graves disease (275000), respectively. Hildebrand et al. (2008) noted that polymorphisms in the WFS1 gene (see, e.g., 606201.0021) had been associated with autoimmune disease, and suggested that the autoimmune disease in the 2 family members may be related to variants in the WFS1 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, VAL707PHE AND 1-BP DEL, 2819C
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs71524377,
|
|
|
|
|
|
gnomAD: rs71524377,
|
|
|
|
|
|
ClinVar: RCV000023510, RCV003553890, RCV003778168
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 20 Lebanese patients from 8 families ascertained with juvenile-onset insulin-dependent diabetes (222100), Zalloua et al. (2008) identified homozygosity for a complex mutation in exon 8 of the WFS1 gene, which they designated WFS1(LIB), consisting of a 2289G-A transition, resulting in a val707-to-phe (V707F) substitution, and a 1-bp del (2819delC), resulting in a frameshift predicted to cause premature termination. The mutations were in complete linkage disequilibrium and were consistently associated with the same haplotype. Eight of the 20 patients were diagnosed with Wolfram syndrome (WFS1; 222300), whereas 10 had only nonsyndromic nonautoimmune diabetes mellitus (DM); the remaining 2 patients were given an initial diagnosis of nonsyndromic DM that was revised to WFS when they developed optic atrophy during the course of the study. Another Lebanese patient with nonsyndromic DM was found to be compound heterozygous for the complex mutation and an 8-bp deletion in exon 8 of the WFS1 gene (606201.0025), resulting in a frameshift predicted to cause premature termination. This frameshift mutation (Phe646fs708Ter) was also found in 4 patients with a diagnosis of Wolfram syndrome. Zalloua et al. (2008) noted that follow-up of these WFS1-mutated nonsyndromic DM patients or a specific study of adult patient populations would be needed to determine whether a subset of the WFS1(LIB) patients are exempted from extrapancreatic manifestations during their lifetime. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, 8-BP DEL, NT2106
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs71524374,
|
|
|
|
|
|
|
|
ClinVar: RCV000023511
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 8-bp deletion in the WFS1 gene that was found in patients with Wolfram syndrome (WFS1; 222300) or nonsyndromic nonautoimmune diabetes mellitus by Zalloua et al. (2008), see 606201.0024. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 WOLFRAM-LIKE SYNDROME, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, ARG228GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs150771247,
|
|
|
|
|
|
gnomAD: rs150771247,
|
|
|
|
|
|
ClinVar: RCV000023512, RCV000200201, RCV000515386, RCV000724125, RCV001155463, RCV001155464, RCV004537488, RCV004816299
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg228-to-gln (R228Q) mutation in the WFS1 gene that was found in compound heterozygous state in a patient with congenital hearing impairment and noninsulin-dependent diabetes (see WFSL, 614296) by Valero et al. (2008), see 606201.0020. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 WOLFRAM-LIKE SYNDROME, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, LYS836ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs876657675,
|
|
|
|
|
|
|
|
ClinVar: RCV000023513, RCV000219504
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected members of a Dutch family segregating autosomal dominant deafness and optic neuropathy (WFSL; 614296), Hogewind et al. (2010) identified heterozygosity for a 2508G-C transversion in exon 8 of the WFS1 gene, resulting in a lys836-to-asn (K836N) substitution at a highly conserved residue within a conserved region of the protein. The mutation was not found in unaffected family members or in 200 European chromosomes. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 WOLFRAM-LIKE SYNDROME, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
WOLFRAM SYNDROME 1, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, ALA684VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906930,
|
|
|
|
|
|
gnomAD: rs387906930,
|
|
|
|
|
|
ClinVar: RCV000023514, RCV000023515, RCV000200668, RCV000605882, RCV000623116, RCV001542531, RCV002280094, RCV004808555, RCV004814922
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of 6 unrelated families segregating autosomal dominant hearing loss and optic atrophy (WFSL; 614296), including the Swedish family originally reported by Samuelson (1940), Rendtorff et al. (2011) identified heterozygosity for a 2051C-T transition in exon 8 of the WFS1 gene, resulting in an ala684-to-val (A684V) substitution at a highly conserved residue in the hydrophilic C terminus. The mutation was not found in 298 ethnically matched control chromosomes. Haplotype analysis suggested that the A684V mutation arose independently in the families studied and may thus represent a mutation hotspot. In 5 of the 6 families, there were spouses with isolated deafness, prompting analysis of the GJB2 gene (121011), which revealed that 2 of the probands also carried known SNHL-related mutations in the GJB2 gene (121011.0001 or 121011.0005) inherited from a deaf parent who did not have optic atrophy. In 1 family, the proband's asymptomatic wife carried a 3-bp deletion (1243delGTC; 606201.0029) in the WFS1 gene, resulting in deletion of val415 (V415del); their 2 children were compound heterozygotes for the deletion and A684V mutation, and both were diagnosed with Wolfram syndrome (WFS1; 222300) based on juvenile-onset diabetes mellitus, optic atrophy, bilateral profound sensorineural hearing loss from birth or infancy, and congenital cataracts. Functional expression analysis in transiently transfected HEK cells demonstrated that both A684V and V415del greatly reduced protein expression compared to wildtype. Rendtorff et al. (2011) noted that A684V had previously been reported in an Italian patient with Wolfram syndrome (Tessa et al., 2001) in compound heterozygosity with a 4-bp deletion (1387delCTCT; 606201.0030) in the WFS1 gene. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, 3-BP DEL, VAL415DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs863224265,
|
|
|
|
|
|
|
|
ClinVar: RCV000199829, RCV000611263, RCV001843422, RCV001849340, RCV002478696, RCV004541271
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 3-bp deletion in the WFS1 gene (1243delGTC) that was found in compound heterozygous state in sibs with Wolfram syndrome (WFS1; 222300) by Rendtorff et al. (2011), see 606201.0028. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 WOLFRAM SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, 4-BP DEL, 1387CTCT
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs760337383,
|
|
|
|
|
|
gnomAD: rs760337383,
|
|
|
|
|
|
ClinVar: RCV000494474, RCV000778738, RCV001672804, RCV002252138, RCV002481565, RCV004535551, RCV004816729
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the 4-bp deletion in the WFS1 gene (1387delCTCT) that was found in compound heterozygous state in a patient with Wolfram syndrome (WFS1; 222300) by Tessa et al. (2001), see 606201.0028. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 WOLFRAM-LIKE SYNDROME, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, GLY780SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906931,
|
|
|
|
|
|
|
|
ClinVar: RCV000023518, RCV001762055
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a sister and brother and their affected mother from a Caucasian UK family segregating autosomal dominant hearing loss and optic atrophy (WFSL; 614296), Rendtorff et al. (2011) identified heterozygosity for a 2338G-A transition in exon 8 of the WFS1 gene, resulting in a gly780-to-ser (G780S) substitution at a conserved residue in the hydrophilic C terminus. The mutation was not found in 298 ethnically matched control chromosomes, and functional analysis in transiently transfected HEK cells demonstrated that G780S mildly decreased protein expression compared to wildtype. The 14-year-old sister was reported to have bilateral prelingual profound hearing loss and optic atrophy, with normal plasma glucose and urine osmolality, and her 9-year-old affected brother had also been diagnosed with autism. Their 48-year-old affected mother also had schizophrenia and had been treated for psychosis; she had an affected brother and sister. The sibs' father, who had isolated sensorineural hearing loss (SNHL), was homozygous for a known SNHL-related mutation in the GJB2 gene (35delG; 121011.0005), and the sibs were both heterozygous for that mutation as well. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0032 CATARACT 41 (1 family)</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
WFS1, GLU462GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs398123066,
|
|
|
|
|
|
gnomAD: rs398123066,
|
|
|
|
|
|
ClinVar: RCV000077875, RCV004597741
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a 4-generation family of Irish descent with congenital nuclear cataract (CTRCT41; 116400), Berry et al. (2013) identified heterozygosity for a c.1385A-G transition in exon 8 of the WFS1 gene, resulting in a glu462-to-gly (E462G) substitution at a highly conserved residue in the cytoplasmic loop linking transmembrane domains 4 and 5. The mutation was not found in unaffected family members or in 100 white European controls. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Berry, V., Gregory-Evans, C., Emmett, W., Waseem, N., Raby, J., Prescott, D., Moore, A. T., Bhattacharya, S. S.
|
|
<strong>Wolfram gene (WFS1) mutation causes autosomal dominant congenital nuclear cataract in humans.</strong>
|
|
Europ. J. Hum. Genet. 21: 1356-1360, 2013.
|
|
|
|
|
|
[PubMed: 23531866]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ejhg.2013.52]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bespalova, I. N., Van Camp, G., Bom, S. J. H., Brown, D. J., Cryns, K., DeWan, A. T., Erson, A. E., Flothmann, K., Kunst, H. P. M., Kurnool, P., Sivakumaran, T. A., Cremers, C. W. R. J., Leal, S. M., Burmeister, M., Lesperance, M. M.
|
|
<strong>Mutations in the Wolfram syndrome 1 gene (WFS1) are a common cause of low frequency sensorineural hearing loss.</strong>
|
|
Hum. Molec. Genet. 10: 2501-2508, 2001.
|
|
|
|
|
|
[PubMed: 11709537]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.22.2501]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Colosimo, A., Guida, V., Rigoli, L., Di Bella, C., De Luca, A., Briuglia, S., Stuppia, L., Salpietro, D. C., Dallapiccolo, B.
|
|
<strong>Molecular detection of novel WFS1 mutations in patients with Wolfram syndrome by a DHPLC-based assay.</strong>
|
|
Hum. Mutat. 21: 622-629, 2003.
|
|
|
|
|
|
[PubMed: 12754709]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.10215]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cryns, K., Pfister, M., Pennings, R. J. E., Bom, S. J. H., Flothmann, K., Caethoven, G., Kremer, H., Schatteman, I., Koln, K. A., Toth, T., Kupka, S., Blin, N., Nurnberg, P., Thiele, H., van de Heyning, P. H., Reardon, W., Stephens, D., Cremers, C. W. R. J., Smith, R. J. H., Van Camp, G.
|
|
<strong>Mutations in the WFS1 gene that cause low-frequency sensorineural hearing loss are small non-inactivating mutations.</strong>
|
|
Hum. Genet. 110: 389-394, 2002.
|
|
|
|
|
|
[PubMed: 12073007]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-002-0719-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cryns, K., Sivakumaran, T. A., Van den Ouweland, J. M. W., Pennings, R. J. E., Cremers, C. W. R. J., Flothmann, K., Young, T.-L., Smith, R. J. H., Lesperance, M. M., Van Camp, G.
|
|
<strong>Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease.</strong>
|
|
Hum. Mutat. 22: 275-287, 2003.
|
|
|
|
|
|
[PubMed: 12955714]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.10258]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Domenech, E., Gomez-Zaera, M., Nunes, V.
|
|
<strong>WFS1 mutations in Spanish patients with diabetes mellitus and deafness.</strong>
|
|
Europ. J. Hum. Genet. 10: 421-426, 2002.
|
|
|
|
|
|
[PubMed: 12107816]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5200823]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Domenech, E., Gomez-Zaera, M., Nunes, V.
|
|
<strong>Study of the WFS1 gene and mitochondrial DNA in Spanish Wolfram syndrome families.</strong>
|
|
Clin. Genet. 65: 463-469, 2004.
|
|
|
|
|
|
[PubMed: 15151504]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.2004.00249.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eiberg, H., Hansen, L., Kjer, B., Hansen, T., Pedersen, O., Bille, M., Rosenberg, T., Tranebjaerg, L.
|
|
<strong>Autosomal dominant optic atrophy associated with hearing impairment and impaired glucose regulation caused by a missense mutation in the WFS1 gene.</strong>
|
|
J. Med. Genet. 43: 435-440, 2006.
|
|
|
|
|
|
[PubMed: 16648378]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2005.034892]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fonseca, S. G., Fukuma, M., Lipson, K. L., Nguyen, L. X., Allen, J. R., Oka, Y., Urano, F.
|
|
<strong>WFS1 is a novel component of the unfolded protein response and maintains homeostasis of the endoplasmic reticulum in pancreatic beta-cells.</strong>
|
|
J. Biol. Chem. 280: 39609-39615, 2005.
|
|
|
|
|
|
[PubMed: 16195229]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M507426200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fukuoka, H., Kanda, Y., Ohta, S., Usami, S.
|
|
<strong>Mutations in the WFS1 gene are a frequent cause of autosomal dominant nonsyndromic low-frequency hearing loss in Japanese.</strong>
|
|
J. Hum. Genet. 52: 510-515, 2007.
|
|
|
|
|
|
[PubMed: 17492394]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10038-007-0144-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gomez-Zaera, M., Strom, T. M., Rodriguez, B., Estivill, X., Meitinger, T., Nunes, V.
|
|
<strong>Presence of a major WFS1 mutation in Spanish Wolfram syndrome pedigrees.</strong>
|
|
Molec. Genet. Metab. 72: 72-81, 2001.
|
|
|
|
|
|
[PubMed: 11161832]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/mgme.2000.3107]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hansen, L., Eiberg, H., Barrett, T., Bek, T., Kjaersgaard, P., Tranebjaerg, L., Rosenberg, T.
|
|
<strong>Mutation analysis of the WFS1 gene in seven Danish Wolfram syndrome families; four new mutations identified.</strong>
|
|
Europ. J. Hum. Genet. 13: 1275-1284, 2005.
|
|
|
|
|
|
[PubMed: 16151413]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5201491]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hardy, C., Khanim, F., Torres, R., Scott-Brown, M., Seller, A., Poulton, J., Collier, D., Kirk, J., Polymeropoulos, M., Latif, F., Barrett, T.
|
|
<strong>Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1.</strong>
|
|
Am. J. Hum. Genet. 65: 1279-1290, 1999.
|
|
|
|
|
|
[PubMed: 10521293]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302609]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hildebrand, M. S., Sorensen, J. L., Jensen, M., Kimberling, W. J., Smith, R. J. H.
|
|
<strong>Autoimmune disease in a DFNA6/14/38 family carrying a novel missense mutation in WFS1.</strong>
|
|
Am. J. Med. Genet. 146A: 2258-2265, 2008.
|
|
|
|
|
|
[PubMed: 18688868]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.32449]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hofmann, S., Bauer, M. F.
|
|
<strong>Wolfram syndrome-associated mutations lead to instability and proteasomal degradation of wolframin.</strong>
|
|
FEBS Lett. 580: 4000-4004, 2006.
|
|
|
|
|
|
[PubMed: 16806192]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.febslet.2006.06.036]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hofmann, S., Philbrook, C., Gerbitz, K.-D., Bauer, M. F.
|
|
<strong>Wolfram syndrome: structural and functional analyses of mutant and wild-type wolframin, the WFS1 gene product.</strong>
|
|
Hum. Molec. Genet. 12: 2003-2012, 2003.
|
|
|
|
|
|
[PubMed: 12913071]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg214]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hogewind, B. F. T., Pennings, R. J. E., Hol, F. A., Kunst, H. P. M., Hoefsloot, E. H., Cruysberg, J. R. M., Cremers, C. W. R. J.
|
|
<strong>Autosomal dominant optic neuropathy and sensorineural hearing loss associated with a novel mutation of WFS1.</strong>
|
|
Molec. Vis. 16: 26-35, 2010.
|
|
|
|
|
|
[PubMed: 20069065]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Inoue, H., Tanizawa, Y., Wasson, J., Behn, P., Kalidas, K., Bernal-Mizrachi, E., Meuckler, M., Marshall, H., Donis-Keller, H., Crock, P., Rogers, D., Mikuni, M., Kumashiro, H., Higashi, K., Sobue, G., Oka, Y., Permutt, M. A.
|
|
<strong>A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).</strong>
|
|
Nature Genet. 20: 143-148, 1998.
|
|
|
|
|
|
[PubMed: 9771706]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/2441]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ishihara, H., Takeda, S., Tamura, A., Takahashi, R., Yamaguchi, S., Takei, D., Yamada, T., Inoue, H., Soga, H., Katagiri, H., Tanizawa, Y., Oka, Y.
|
|
<strong>Disruption of the WFS1 gene in mice causes progressive beta-cell loss and impaired stimulus-secretion coupling in insulin secretion.</strong>
|
|
Hum. Molec. Genet. 13: 1159-1170, 2004.
|
|
|
|
|
|
[PubMed: 15056606]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddh125]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Khanim, F., Kirk, J., Latif, F., Barrett, T. G.
|
|
<strong>WFS1/Wolframin mutations, Wolfram syndrome, and associated diseases.</strong>
|
|
Hum. Mutat. 17: 357-367, 2001.
|
|
|
|
|
|
[PubMed: 11317350]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1110]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Komatsu, K., Nakamura, N., Ghadami, M., Matsumoto, N., Kishino, T., Ohta, T., Niikawa, N., Yoshiura, K.
|
|
<strong>Confirmation of genetic homogeneity of nonsyndromic low-frequency sensorineural hearing loss by linkage analysis and a DFNA6/14 mutation in a Japanese family.</strong>
|
|
J. Hum. Genet. 47: 395-399, 2002.
|
|
|
|
|
|
[PubMed: 12181639]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s100380200057]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lesperance, M. M., Hall, J. W., III, Bess, F. H., Fukushima, K., Jain, P. K., Ploplis, B., San Agustin, T. B., Skarka, H., Smith, R. J. H., Wills, M., Wilcox, E. R.
|
|
<strong>A gene for autosomal dominant nonsyndromic hereditary hearing impairment maps to 4p16.3.</strong>
|
|
Hum. Molec. Genet. 4: 1967-1972, 1995.
|
|
|
|
|
|
[PubMed: 8595423]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/4.10.1967]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Osman, A. A., Saito, M., Makepeace, C., Permutt, M. A., Schlesinger, P., Mueckler, M.
|
|
<strong>Wolframin expression induces novel ion channel activity in endoplasmic reticulum membranes and increases intracellular calcium.</strong>
|
|
J. Biol. Chem. 278: 52755-52762, 2003.
|
|
|
|
|
|
[PubMed: 14527944]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M310331200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rendtorff, N. D., Lodahl, M., Boulahbel, H., Johansen, I. R., Pandya, A., Welch, K. O., Norris, V. W., Arnos, K. S., Bitner-Glindzicz, M., Emery, S. B., Mets, M. B., Fagerheim, T., Eriksson, K., Hansen, L., Bruhn, H., Moller, C., Lindholm, S., Ensgaard, S., Lesperance, M. M., Tranebjaerg, L.
|
|
<strong>Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment.</strong>
|
|
Am. J. Med. Genet. 155A: 1298-1313, 2011.
|
|
|
|
|
|
[PubMed: 21538838]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.33970]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sam, W., Qin, H., Crawford, B., Yue, D., Yu, S.
|
|
<strong>Homozygosity for a 4-bp deletion in a patient with Wolfram syndrome suggesting possible phenotype and genotype correlation. (Letter)</strong>
|
|
Clin. Genet. 59: 136-138, 2001.
|
|
|
|
|
|
[PubMed: 11260218]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1034/j.1399-0004.2001.590214.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Samuelson, A.
|
|
<strong>Familjart upptradande synnervsatrofi och dovhet.</strong>
|
|
Nord. Med. 6: 769-772, 1940.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sandhu, M. S., Weedon, M. N., Fawcett, K. A., Wasson, J., Debenham, S. L., Daly, A., Lango, H., Frayling, T. M., Neumann, R. J., Sherva, R., Blech, I., Pharoah, P. D., and 12 others.
|
|
<strong>Common variants in WFS1 confer risk of type 2 diabetes.</strong>
|
|
Nature Genet. 39: 951-953, 2007.
|
|
|
|
|
|
[PubMed: 17603484]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng2067]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Strom, T. M., Hortnagel, K., Hofmann, S., Gekeler, F., Scharfe, C., Rabl, W., Gerbitz, K. D., Meitinger, T.
|
|
<strong>Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein.</strong>
|
|
Hum. Molec. Genet. 7: 2021-2028, 1998.
|
|
|
|
|
|
[PubMed: 9817917]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/7.13.2021]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Takeda, K., Inoue, K., Tanizawa, Y., Matsuzaki, Y., Oba, J., Watanabe Y., Shinoda, K., Oka, Y.
|
|
<strong>WFS1 (Wolfram syndrome 1) gene product: predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain.</strong>
|
|
Hum. Molec. Genet. 10: 477-484, 2001.
|
|
|
|
|
|
[PubMed: 11181571]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.5.477]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tessa, A., Carbone, I., Matteoli, M. C., Bruno, C., Patrono, C., Patera, I. P., De Luca, F., Lorini, R., Santorelli, F. M.
|
|
<strong>Identification of novel WFS1 mutations in Italian children with Wolfram syndrome.</strong>
|
|
Hum. Mutat. 17: 348-349, 2001.
|
|
|
|
|
|
[PubMed: 11295831]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.32]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Valero, R., Bannwarth, S., Roman, S., Paquis-Flucklinger, V., Vialettes, B.
|
|
<strong>Autosomal dominant transmission of diabetes and congenital hearing impairment secondary to a missense mutation in the WFS1 gene.</strong>
|
|
Diabet. Med. 25: 657-661, 2008.
|
|
|
|
|
|
[PubMed: 18544103]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1464-5491.2008.02448.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Young, T.-L., Ives, E., Lynch, E., Person, R., Snook, S., MacLaren, L., Cater, T., Griffin, A., Fernandez, B., Lee, M. K., King, M.-C.
|
|
<strong>Non-syndromic progressive hearing loss DFNA38 is caused by heterozygous missense mutation in the Wolfram syndrome gene WFS1.</strong>
|
|
Hum. Molec. Genet. 10: 2509-2514, 2001. Note: Erratum: Hum. Molec. Genet. 10: 3111 only, 2001.
|
|
|
|
|
|
[PubMed: 11709538]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.22.2509]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zalloua, P. A., Azar, S. T., Delepine, M., Makhoul, N. J., Blanc, H., Sanyoura, M., Lavergne, A., Stankov, K., Lemainque, A., Baz, P., Julier, C.
|
|
<strong>WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon.</strong>
|
|
Hum. Molec. Genet. 17: 4012-4021, 2008.
|
|
|
|
|
|
[PubMed: 18806274]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddn304]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zatyka, M., Ricketts, C., Xavier, G. S., Minton, J., Fenton, S., Hofmann-Thiel, S., Rutter, G. A., Barrett, T. G.
|
|
<strong>Sodium-potassium ATPase beta-1 subunit is a molecular partner of Wolframin, an endoplasmic reticulum protein involved in ER stress.</strong>
|
|
Hum. Molec. Genet. 17: 190-200, 2008.
|
|
|
|
|
|
[PubMed: 17947299]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddm296]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Marla J. F. O'Neill - updated : 1/14/2014<br>Marla J. F. O'Neill - updated : 10/19/2011<br>Marla J. F. O'Neill - updated : 9/22/2011<br>Marla J. F. O'Neill - updated : 6/1/2009<br>Matthew B. Gross - updated : 5/13/2009<br>Patricia A. Hartz - updated : 5/4/2009<br>Cassandra L. Kniffin - updated : 1/5/2009<br>Marla J. F. O'Neill - updated : 9/25/2007<br>George E. Tiller - updated : 9/6/2006<br>Marla J. F. O'Neill - updated : 6/16/2006<br>Cassandra L. Kniffin - updated : 3/2/2006<br>George E. Tiller - updated : 6/3/2005<br>Victor A. McKusick - updated : 6/23/2004<br>Victor A. McKusick - updated : 10/23/2003<br>Victor A. McKusick - updated : 7/11/2003<br>Michael B. Petersen - updated : 5/15/2003<br>Victor A. McKusick - updated : 11/11/2002<br>Victor A. McKusick - updated : 8/6/2002<br>Victor A. McKusick - updated : 6/7/2002<br>George E. Tiller - updated : 5/7/2002<br>George E. Tiller - updated : 12/13/2001<br>Ada Hamosh - reorganized : 8/15/2001
|
|
</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 : 8/14/2001
|
|
</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 : 03/06/2024<br>carol : 09/04/2020<br>carol : 09/03/2020<br>carol : 09/02/2020<br>carol : 04/24/2018<br>alopez : 07/27/2015<br>mcolton : 7/21/2015<br>carol : 1/14/2014<br>carol : 9/16/2013<br>carol : 8/5/2013<br>carol : 8/5/2013<br>alopez : 4/25/2013<br>terry : 6/20/2012<br>carol : 2/13/2012<br>terry : 10/26/2011<br>terry : 10/19/2011<br>carol : 10/19/2011<br>carol : 9/23/2011<br>terry : 9/22/2011<br>alopez : 6/4/2010<br>wwang : 2/25/2010<br>wwang : 6/2/2009<br>terry : 6/1/2009<br>mgross : 5/13/2009<br>terry : 5/4/2009<br>wwang : 1/8/2009<br>ckniffin : 1/5/2009<br>terry : 12/2/2008<br>alopez : 11/12/2007<br>alopez : 9/25/2007<br>alopez : 9/6/2006<br>wwang : 6/16/2006<br>wwang : 3/2/2006<br>alopez : 6/3/2005<br>terry : 3/3/2005<br>tkritzer : 6/28/2004<br>terry : 6/23/2004<br>terry : 3/24/2004<br>carol : 3/5/2004<br>cwells : 10/23/2003<br>terry : 10/23/2003<br>cwells : 7/16/2003<br>terry : 7/11/2003<br>cwells : 5/15/2003<br>alopez : 11/13/2002<br>terry : 11/11/2002<br>carol : 8/8/2002<br>tkritzer : 8/7/2002<br>terry : 8/6/2002<br>alopez : 6/12/2002<br>terry : 6/7/2002<br>alopez : 5/7/2002<br>alopez : 5/7/2002<br>cwells : 1/11/2002<br>cwells : 12/13/2001<br>carol : 8/22/2001<br>carol : 8/21/2001<br>carol : 8/15/2001<br>carol : 8/15/2001
|
|
</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>
|
|
|
|
|