7526 lines
683 KiB
Text
7526 lines
683 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
|
|
|
|
- *300473 - NUCLEAR RECEPTOR SUBFAMILY 0, GROUP B, MEMBER 1; NR0B1
|
|
|
|
|
|
- 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=300473"><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">*300473</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneStructure">Gene Structure</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/300473">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=ENSG00000169297;t=ENST00000378970" 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=190" 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=300473" 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=ENSG00000169297;t=ENST00000378970" 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_000475" 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_000475" 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=300473" 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=08362&isoform_id=08362_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/NR0B1" 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/786532,1163077,5016090,15079454,20532385,119619457,325495475,1214150028" 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/P51843" 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=190" 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=ENSG00000169297;t=ENST00000378970" 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=NR0B1" 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=NR0B1" 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+190" 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/NR0B1" 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:190" 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/190" 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=chrX&hgg_gene=ENST00000378970.5&hgg_start=30304206&hgg_end=30309390&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:7960" 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=300473[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=300473[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://gnomad.broadinstitute.org/gene/ENSG00000169297" 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.gwascentral.org/search?q=NR0B1" 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=NR0B1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.LOVD.nl/NROB1" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=NR0B1&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/PA31746" 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:7960" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:1352460" 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/NR0B1#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:1352460" 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/190/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://omia.org/OMIA002060/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=190" 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-070130-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="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:190" 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=NR0B1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 93235007<br />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
300473
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
NUCLEAR RECEPTOR SUBFAMILY 0, GROUP B, MEMBER 1; NR0B1
|
|
|
|
</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">
|
|
DSS-AHC CRITICAL REGION ON THE X CHROMOSOME 1, GENE 1; DAX1
|
|
</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=NR0B1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">NR0B1</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/X/144?start=-3&limit=10&highlight=144">Xp21.2</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:30304206-30309390&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'})">X:30,304,206-30,309,390</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=300018,300200" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/X/144?start=-3&limit=10&highlight=144">
|
|
Xp21.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
46XY sex reversal 2, dosage-sensitive
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/300018"> 300018 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked">XL</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">
|
|
Adrenal hypoplasia, congenital
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/300200"> 300200 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</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/300473" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/300473" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>NR0B1 (DAX1) is an orphan member of the nuclear receptor (NR) superfamily. It functions in the proper formation of the adult adrenal gland. NR0B1 has a unique role as an NR in that it acts as a coregulatory protein that inhibits the transcriptional activity of other NRs (review by <a href="#33" class="mim-tip-reference" title="Niakan, K. K., McCabe, E. R. B. <strong>DAX1 origin, function, and novel role.</strong> Molec. Genet. Metab. 86: 70-83, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16146703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16146703</a>] [<a href="https://doi.org/10.1016/j.ymgme.2005.07.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16146703">Niakan and McCabe, 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16146703" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>By identifying ESTs from the dosage-sensitive sex reversal (DSS; <a href="/entry/300018">300018</a>)-congenital adrenal hypoplasia (AHC; <a href="/entry/300200">300200</a>) critical region, <a href="#53" class="mim-tip-reference" title="Zanaria, E., Muscatelli, F., Bardoni, B., Strom, T. M., Guioli, S., Guo, W., Lalli, E., Moser, C., Walker, A. P., McCabe, E. R. B., Meitinger, T., Monaco, A. P., Sassone-Corsi, P., Camerino, G. <strong>An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita.</strong> Nature 372: 635-641, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7990953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7990953</a>] [<a href="https://doi.org/10.1038/372635a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7990953">Zanaria et al. (1994)</a> screened human adult testis and human fetal adrenal cDNA libraries and isolated the NR0B1 gene, which they designated DAX1. The DAX1 gene encodes a deduced 470-amino acid protein that belongs to the nuclear hormone receptor superfamily and displays a novel DNA-binding domain at the N terminus. The C terminus shows characteristics of a nuclear hormone receptor ligand-binding domain. Highly significant similarity was found between the C-terminal half of DAX1 and the ligand-binding domain (domain E) of the retinoid X receptor subfamily (e.g., RXRG; <a href="/entry/180247">180247</a>). Northern blot analysis detected a 1.9-kb DAX1 mRNA in adult testis and adrenal tissue. Zoo blots showed homologous fragments in all species tested, including chicken, but not in Drosophila melanogaster. Dosage analysis suggested that the cross-hybridizing fragments in mammals are X-linked. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7990953" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 Northern blot analysis, <a href="#9" class="mim-tip-reference" title="Guo, W., Burris, T. P., McCabe, E. R. B. <strong>Expression of DAX-1, the gene responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism, in the hypothalamic-pituitary-adrenal/gonadal axis.</strong> Biochem. Molec. Med. 56: 8-13, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8593542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8593542</a>] [<a href="https://doi.org/10.1006/bmme.1995.1049" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8593542">Guo et al. (1995)</a> found that DAX1 was expressed in the hypothalamus and pituitary, in addition to the gonads and adrenal cortex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8593542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Guo, W., Lovell, R. S., Zhang, Y.-H., Huang, B.-L., Burris, T. P., Craigen, W. J., McCabe, E. R. B. <strong>Ahch, the mouse homologue of DAX1: cloning, characterization and synteny with GyK, the glycerol kinase locus.</strong> Gene 178: 31-34, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8921887/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8921887</a>] [<a href="https://doi.org/10.1016/0378-1119(96)00320-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8921887">Guo et al. (1996)</a> cloned Ahch, the mouse homolog of DAX1. They noted that the cysteine residues of the putative zinc finger DNA-binding region of DAX1 are conserved in Ahch, suggesting that this region is functional. <a href="#44" class="mim-tip-reference" title="Swain, A., Zanaria, E., Hacker, A., Lovell-Badge, R., Camerino, G. <strong>Mouse Dax1 expression is consistent with a role in sex determination as well as in adrenal and hypothalamus function.</strong> Nature Genet. 12: 404-409, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8630494/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8630494</a>] [<a href="https://doi.org/10.1038/ng0496-404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8630494">Swain et al. (1996)</a> isolated the mouse Dax1 gene and found that the coding sequences of human and mouse DAX1 are more similar at the DNA than at the protein levels, suggesting rapid evolution. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8630494+8921887" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 3-prime RACE of a testis cDNA library, <a href="#14" class="mim-tip-reference" title="Hossain, A., Li, C., Saunders, G. F. <strong>Generation of two distinct functional isoforms of dosage-sensitive sex reversal-adrenal hypoplasia congenita-critical region on the X chromosome gene 1 (DAX-1) by alternative splicing.</strong> Molec. Endocr. 18: 1428-1437, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15044589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15044589</a>] [<a href="https://doi.org/10.1210/me.2003-0176" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15044589">Hossain et al. (2004)</a> cloned a splice variant of DAX1 that they called DAX1-alpha. The deduced 401-amino acid DAX1-alpha protein is identical to DAX1 for the first 389 amino acids, including 3.5 repeats of a 65- to 67-amino acid sequence rich in alanine and glycine. However, DAX1-alpha has a unique 12-amino acid C terminus instead of the transcriptional repression domain of DAX1. RT-PCR showed highest expression of DAX1-alpha in adult testis, followed by fetal kidney and adult adrenal gland, brain, pancreas, ovary, breast, and thymus, with low expression in all other adult tissues examined. DAX1 showed highest expression in adult testis, with much lower levels in fetal kidney and adult adrenal gland, brain, ovary, and pancreas, and no expression in all other tissues examined. Real-time RT-PCR showed that DAX1-alpha predominated in all tissues tested except testis, where DAX1 predominated. Western blot analysis using an antibody directed to the common N terminus of DAX1 and DAX1-alpha detected high levels of both proteins in testis and much weaker expression of DAX1-alpha only in breast. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15044589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Ho, J., Zhang, Y.-H., Huang, B.-L., McCabe, E. R. B. <strong>NR0B1A: an alternatively spliced form of NR0B1.</strong> Molec. Genet. Metab. 83: 330-336, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15589120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15589120</a>] [<a href="https://doi.org/10.1016/j.ymgme.2004.10.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15589120">Ho et al. (2004)</a> identified a DAX1 splice variant similar to DAX1-alpha that they called DAX1A. The deduced 400-amino acid DAX1A protein is identical to DAX1 over the first 389 amino acids. DAX1A differs at its C-terminal end from the DAX1-alpha protein reported by <a href="#14" class="mim-tip-reference" title="Hossain, A., Li, C., Saunders, G. F. <strong>Generation of two distinct functional isoforms of dosage-sensitive sex reversal-adrenal hypoplasia congenita-critical region on the X chromosome gene 1 (DAX-1) by alternative splicing.</strong> Molec. Endocr. 18: 1428-1437, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15044589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15044589</a>] [<a href="https://doi.org/10.1210/me.2003-0176" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15044589">Hossain et al. (2004)</a>. RT-PCR detected highest DAX1A expression in testis, ovary, and adrenal gland, with weaker expression in pancreas. DAX1 showed highest expression in lung, pancreas, testis, ovary, and adrenal gland, with weaker expression in brain, spleen, thymus, prostate, and small intestine. Database analysis suggested the presence of DAX1A in chimpanzee, but not in rodent or chicken. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15044589+15589120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Iyer, A. K., Zhang, Y.-H., McCabe, E. R. B. <strong>Dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1) (NR0B1) and small heterodimer partner (SHP) (NR0B2) form homodimers individually, as well as DAX1-SHP heterodimers.</strong> Molec. Endocr. 20: 2326-2342, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16709599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16709599</a>] [<a href="https://doi.org/10.1210/me.2005-0383" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16709599">Iyer et al. (2006)</a> stated that each of the 3 full-length N-terminal repeats in DAX1 contains LxxLL nuclear receptor boxes. The C terminus of DAX1 contains a transcriptional silencing domain and an activation factor (AF)-2 domain, and these are absent in DAX1A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16709599" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 immunohistochemistry in rats to analyze NR0B1 expression during steroidogenesis and spermatogenesis, <a href="#18" class="mim-tip-reference" title="Kojima, Y., Sasaki, S., Hayashi, Y., Umemoto, Y., Morohashi, K.-I., Kohri, K. <strong>Role of transcription factors Ad4BP/SF-1 and DAX-1 in steroidogenesis and spermatogenesis in human testicular development and idiopathic azoospermia.</strong> Int. J. Urol. 13: 785-793, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16834661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16834661</a>] [<a href="https://doi.org/10.1111/j.1442-2042.2006.01403.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16834661">Kojima et al. (2006)</a> observed strong expression in both Leydig and Sertoli cells. The intensity of expression was the same at all 14 cyclical stages of spermatogenesis in 7-day- and 21-day-old rats, but showed a stage-specific pattern in the 56-day-old sexually mature rat, with peak immunostaining during spermatogenesis stages VII to XII, coinciding with stages of major events in spermatogenesis. In humans, quantitative RT-PCR and Western blot analysis of testicular tissue obtained from males at ages ranging from 1 year to 26 years showed increased expression with increasing age during testicular development. In pubertal and adult testes, NR0B1 was abundantly expressed in the nuclei of Sertoli cells, but only a few Leydig cells were faintly NR0B1-positive. <a href="#18" class="mim-tip-reference" title="Kojima, Y., Sasaki, S., Hayashi, Y., Umemoto, Y., Morohashi, K.-I., Kohri, K. <strong>Role of transcription factors Ad4BP/SF-1 and DAX-1 in steroidogenesis and spermatogenesis in human testicular development and idiopathic azoospermia.</strong> Int. J. Urol. 13: 785-793, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16834661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16834661</a>] [<a href="https://doi.org/10.1111/j.1442-2042.2006.01403.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16834661">Kojima et al. (2006)</a> concluded that expression of NR0B1 is developmentally regulated, with maximal expression during puberty and high expression after puberty. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16834661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 Western blot analysis, <a href="#17" class="mim-tip-reference" title="Kang, Y., Zheng, B., Shen, B., Chen, Y., Wang, L., Wang, J., Niu, Y., Cui, Y., Zhou, J., Wang, H., Guo, X., Hu, B., Zhou, Q., Sha, J., Ji, W., Huang, X. <strong>CRISPR/Cas9-mediated Dax1 knockout in the monkey recapitulates human AHC-HH.</strong> Hum. Molec. Genet. 24: 7255-7264, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26464492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26464492</a>] [<a href="https://doi.org/10.1093/hmg/ddv425" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26464492">Kang et al. (2015)</a> detected Dax1 expression in testis, adrenal gland, placenta, and ovary of cynomolgus monkey. Dax1 expression was absent in heart, liver, spleen, lung, kidney, skeletal muscle, small intestine, brain, and uterus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26464492" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#53" class="mim-tip-reference" title="Zanaria, E., Muscatelli, F., Bardoni, B., Strom, T. M., Guioli, S., Guo, W., Lalli, E., Moser, C., Walker, A. P., McCabe, E. R. B., Meitinger, T., Monaco, A. P., Sassone-Corsi, P., Camerino, G. <strong>An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita.</strong> Nature 372: 635-641, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7990953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7990953</a>] [<a href="https://doi.org/10.1038/372635a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7990953">Zanaria et al. (1994)</a> and <a href="#10" class="mim-tip-reference" title="Guo, W., Burris, T. P., Zhang, Y.-H., Huang, B.-L., Mason, J., Copeland, K. C., Kupfer, S. R., Pagon, R. A., McCabe, E. R. B. <strong>Genomic sequence of the DAX1 gene: an orphan nuclear receptor responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.</strong> J. Clin. Endocr. Metab. 81: 2481-2486, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8675564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8675564</a>] [<a href="https://doi.org/10.1210/jcem.81.7.8675564" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8675564">Guo et al. (1996)</a> determined that the DAX1 gene contains 2 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7990953+8675564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#14" class="mim-tip-reference" title="Hossain, A., Li, C., Saunders, G. F. <strong>Generation of two distinct functional isoforms of dosage-sensitive sex reversal-adrenal hypoplasia congenita-critical region on the X chromosome gene 1 (DAX-1) by alternative splicing.</strong> Molec. Endocr. 18: 1428-1437, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15044589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15044589</a>] [<a href="https://doi.org/10.1210/me.2003-0176" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15044589">Hossain et al. (2004)</a> and <a href="#13" class="mim-tip-reference" title="Ho, J., Zhang, Y.-H., Huang, B.-L., McCabe, E. R. B. <strong>NR0B1A: an alternatively spliced form of NR0B1.</strong> Molec. Genet. Metab. 83: 330-336, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15589120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15589120</a>] [<a href="https://doi.org/10.1016/j.ymgme.2004.10.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15589120">Ho et al. (2004)</a> identified an alternatively spliced exon, which they called exon 2-alpha or 2A, respectively, between NR0B1 exons 1 and 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15044589+15589120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#53" class="mim-tip-reference" title="Zanaria, E., Muscatelli, F., Bardoni, B., Strom, T. M., Guioli, S., Guo, W., Lalli, E., Moser, C., Walker, A. P., McCabe, E. R. B., Meitinger, T., Monaco, A. P., Sassone-Corsi, P., Camerino, G. <strong>An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita.</strong> Nature 372: 635-641, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7990953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7990953</a>] [<a href="https://doi.org/10.1038/372635a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7990953">Zanaria et al. (1994)</a> identified the DAX1 gene within the DSS/AHC critical region on the X chromosome. <a href="#11" class="mim-tip-reference" title="Guo, W., Lovell, R. S., Zhang, Y.-H., Huang, B.-L., Burris, T. P., Craigen, W. J., McCabe, E. R. B. <strong>Ahch, the mouse homologue of DAX1: cloning, characterization and synteny with GyK, the glycerol kinase locus.</strong> Gene 178: 31-34, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8921887/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8921887</a>] [<a href="https://doi.org/10.1016/0378-1119(96)00320-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8921887">Guo et al. (1996)</a> found tight linkage between the mouse Ahch, glycerol kinase (<a href="/entry/300474">300474</a>), and dystrophin (<a href="/entry/300377">300377</a>) genes, thus showing that this region is syntenic with the homologous region of the human X chromosome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8921887+7990953" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneFunction" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneFunctionFold" id="mimGeneFunctionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneFunctionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneFunctionFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#53" class="mim-tip-reference" title="Zanaria, E., Muscatelli, F., Bardoni, B., Strom, T. M., Guioli, S., Guo, W., Lalli, E., Moser, C., Walker, A. P., McCabe, E. R. B., Meitinger, T., Monaco, A. P., Sassone-Corsi, P., Camerino, G. <strong>An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita.</strong> Nature 372: 635-641, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7990953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7990953</a>] [<a href="https://doi.org/10.1038/372635a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7990953">Zanaria et al. (1994)</a> found that the DAX1 protein is an unusual member of the nuclear hormone-receptor superfamily and acts as a dominant-negative regulator of transcription mediated by the retinoic acid receptor. The DAX1 protein is localized mainly in the nucleus and can bind to an RA responsive element (RARE). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7990953" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#44" class="mim-tip-reference" title="Swain, A., Zanaria, E., Hacker, A., Lovell-Badge, R., Camerino, G. <strong>Mouse Dax1 expression is consistent with a role in sex determination as well as in adrenal and hypothalamus function.</strong> Nature Genet. 12: 404-409, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8630494/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8630494</a>] [<a href="https://doi.org/10.1038/ng0496-404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8630494">Swain et al. (1996)</a> found that the mouse Dax1 gene is expressed in the first stages of gonadal and adrenal differentiation and in the developing hypothalamus. Moreover, Dax1 expression is downregulated coincident with overt differentiation in the testis, but persists in the developing ovary. They suggested that these results provided a basis for adrenal insufficiency and hypogonadotropic hypogonadism in males affected by congenital adrenal hypoplasia and were consistent with a role for DAX1 in gonadal sex determination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8630494" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#47" class="mim-tip-reference" title="Tamai, K. T., Monaco, L., Alastalo, T.-P., Lalli, E., Parvinen, M., Sassone-Corsi, P. <strong>Hormonal and developmental regulation of DAX-1 expression in Sertoli cells.</strong> Molec. Endocr. 10: 1561-1569, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8961266/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8961266</a>] [<a href="https://doi.org/10.1210/mend.10.12.8961266" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8961266">Tamai et al. (1996)</a> demonstrated that DAX1 is expressed in the Sertoli cells of rat testis. This expression is regulated during spermatogenesis and peaks during the androgen-sensitive phase of the spermatogenic cycle. They also found that DAX1 expression in Sertoli cells is regulated developmentally. Maximum levels are present in the rat between postnatal days 20 and 30, during the first spermatogenic wave. Furthermore, activation of the cAMP-signaling pathway by follicle-stimulating hormone (FSH; see <a href="/entry/136530">136530</a>) causes downregulation of DAX1 expression in cultured Sertoli cells. These data indicated that DAX1 expression in Sertoli cells may influence the development of spermatogenic cells in response to steroid and pituitary hormones. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8961266" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Binding sites for the DAX1 protein are found in the promoters of the DAX1 and steroidogenic acute regulatory protein (STAR; <a href="/entry/600617">600617</a>) genes. <a href="#54" class="mim-tip-reference" title="Zazopoulos, E., Lalli, E., Stocco, D. M., Sassone-Corsi, P. <strong>DNA binding and transcriptional repression by DAX-1 blocks steroidogenesis.</strong> Nature 390: 311-315, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9384387/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9384387</a>] [<a href="https://doi.org/10.1038/36899" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9384387">Zazopoulos et al. (1997)</a> showed that DAX1 binds DNA and acts as a powerful transcriptional repressor of STAR gene expression, leading to a drastic decrease in steroid production. They provided in vitro and in vivo evidence that DAX1 binds to DNA hairpin structures. The results established that DAX1 is the first member of the nuclear receptor superfamily with novel DNA-binding features. They showed that it has regulatory properties critical to the understanding of its physiologic functions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9384387" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The finding of <a href="#29" class="mim-tip-reference" title="Muscatelli, F., Strom, T. M., Walker, A. P., Zanaria, E., Recan, D., Meindl, A., Bardoni, B., Guioli, S., Zehetner, G., Rabl, W., Schwarz, H. P., Kaplan, J.-C., Camerino, G., Meitinger, T., Monaco, A. P. <strong>Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.</strong> Nature 372: 672-676, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7990958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7990958</a>] [<a href="https://doi.org/10.1038/372672a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7990958">Muscatelli et al. (1994)</a> that point mutations in the DAX1 gene cause AHC and HHG (see MOLECULAR GENETICS) strongly suggested that DAX1 is essential for the development of a functioning hypothalamus-pituitary-gonadal axis. The authors noted that, in mice, disruption of the Ftz-F1 autosomal gene, which encodes the nuclear hormone receptor SF1 (NR5A1; <a href="/entry/184757">184757</a>), prevents the development of adrenal glands and gonads (<a href="#24" class="mim-tip-reference" title="Luo, X., Ikeda, Y., Parker, K. L. <strong>A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation.</strong> Cell 77: 481-490, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8187173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8187173</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90211-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8187173">Luo et al., 1994</a>). In the human male, disruption of DAX1 does not prevent the initial stages of gonadal development, but the adrenal does not differentiate beyond the fetal stage. <a href="#2" class="mim-tip-reference" title="Achermann, J. C., Ito, M., Ito, M., Hindmarsh, P. C., Jameson, J. L. <strong>A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans. (Letter)</strong> Nature Genet. 22: 125-126, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369247</a>] [<a href="https://doi.org/10.1038/9629" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369247">Achermann et al. (1999)</a> found that mutation in the human NR5A1 gene results in XY sex reversal with adrenal failure. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8187173+7990958+10369247" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>DAX1 binds to hairpin secondary structures and blocks steroidogenesis in adrenal cells by transcriptional repression of the STAR promoter. <a href="#19" class="mim-tip-reference" title="Lalli, E., Bardoni, B., Zazopoulos, E., Wurtz, J.-M., Strom, T. M., Moras, D., Sassone-Corsi, P. <strong>A transcriptional silencing domain in DAX-1 whose mutation causes adrenal hypoplasia congenita.</strong> Molec. Endocr. 11: 1950-1960, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9415399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9415399</a>] [<a href="https://doi.org/10.1210/mend.11.13.0038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9415399">Lalli et al. (1997)</a> investigated the molecular mechanism of this repression. They found that the DAX1 C terminus contains transcriptional silencing activity, which can be transferred to a heterologous DNA-binding domain. Two cooperating domains are required for the silencing function, one located within helix H3 and the other within H12. The silencing function is cell- and promoter-specific. By confocal and immunogold electron microscopy, <a href="#20" class="mim-tip-reference" title="Lalli, E., Ohe, K., Hindelang, C., Sassone-Corsi, P. <strong>Orphan receptor DAX-1 is a shuttling RNA binding protein associated with polyribosomes via mRNA.</strong> Molec. Cell. Biol. 20: 4910-4921, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10848616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10848616</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10848616[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.20.13.4910-4921.2000" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10848616">Lalli et al. (2000)</a> showed that DAX1 is localized in both the cytoplasm and nucleus of human adrenal cortex and mouse Leydig tumor cells. Much of the DAX1 is associated with polyribosomes in complexes with polyadenylated RNA. The 3 N-terminal repeats act cooperatively to direct DAX1 binding to RNA, and the C-terminal ligand-binding domain (LBD) also functions as an autonomous RNA-binding domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9415399+10848616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#39" class="mim-tip-reference" title="Reincke, M., Beuschlein, F., Lalli, E., Arlt, W., Vay, S., Sassone-Corsi, P., Allolio, B. <strong>DAX-1 expression in human adrenocortical neoplasms: implications for steroidogenesis.</strong> J. Clin. Endocr. Metab. 83: 2597-2600, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9661652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9661652</a>] [<a href="https://doi.org/10.1210/jcem.83.7.5095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9661652">Reincke et al. (1998)</a> investigated the expression of DAX1 in a variety of adrenocortical tumors and compared the results with STAR mRNA expression. They found low or absent DAX1 expression in aldosterone-producing adenomas and in aldosterone-producing adrenocortical carcinomas. Cortisol-producing adenomas showed intermediate DAX1 expression (n = 8; 92 +/- 16%), as did 3 non-aldosterone-producing carcinomas (72%, 132%, and 132%). High DAX1 expression was present in nonfunctional adenomas (n = 3; 160 +/- 17%). In contrast to DAX1, STAR mRNA expression did not show significant variations between groups. <a href="#39" class="mim-tip-reference" title="Reincke, M., Beuschlein, F., Lalli, E., Arlt, W., Vay, S., Sassone-Corsi, P., Allolio, B. <strong>DAX-1 expression in human adrenocortical neoplasms: implications for steroidogenesis.</strong> J. Clin. Endocr. Metab. 83: 2597-2600, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9661652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9661652</a>] [<a href="https://doi.org/10.1210/jcem.83.7.5095" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9661652">Reincke et al. (1998)</a> concluded that high DAX1 expression in adrenocortical tumors is associated with a nonfunctional phenotype, whereas low DAX1 expression favors mineralocorticoid secretion, and that these effects on steroidogenesis are mediated by mechanisms other than repression of STAR gene expression. They suggested that DAX1 may be one of the factors influencing the steroid biosynthesis of adrenocortical neoplasms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9661652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>XY individuals carrying duplications of Xp21 undergo sex reversal and develop as females. <a href="#43" class="mim-tip-reference" title="Swain, A., Narvaez, V., Burgoyne, P., Camerino, G., Lovell-Badge, R. <strong>Dax1 antagonizes Sry action in mammalian sex determination.</strong> Nature 391: 761-767, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9486644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9486644</a>] [<a href="https://doi.org/10.1038/35799" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9486644">Swain et al. (1998)</a> noted that XY mice carrying extra copies of Dax1 as a transgene show delayed testis development when the gene is expressed at high levels, but do not normally show sex reversal. <a href="#43" class="mim-tip-reference" title="Swain, A., Narvaez, V., Burgoyne, P., Camerino, G., Lovell-Badge, R. <strong>Dax1 antagonizes Sry action in mammalian sex determination.</strong> Nature 391: 761-767, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9486644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9486644</a>] [<a href="https://doi.org/10.1038/35799" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9486644">Swain et al. (1998)</a> found that complete sex reversal occurred, however, when the transgene was tested against weak alleles of the sex-determining Y-chromosome gene Sry (<a href="/entry/480000">480000</a>). These results showed that Dax1 is largely, if not solely, responsible for dosage-sensitive sex reversal and provided a model for early events in mammalian sex determination, when precise levels and timing of gene expression are critical. The results of <a href="#43" class="mim-tip-reference" title="Swain, A., Narvaez, V., Burgoyne, P., Camerino, G., Lovell-Badge, R. <strong>Dax1 antagonizes Sry action in mammalian sex determination.</strong> Nature 391: 761-767, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9486644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9486644</a>] [<a href="https://doi.org/10.1038/35799" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9486644">Swain et al. (1998)</a> indicated that Dax1 functions as an anti-testis gene by acting antagonistically to Sry. The orphan nuclear receptor Dax1 was originally proposed to act as an 'anti-testis' factor. In studies in the mouse, however, <a href="#27" class="mim-tip-reference" title="Meeks, J. J., Weiss, J., Jameson, J. L. <strong>Dax1 is required for testis determination.</strong> Nature Genet. 34: 32-33, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12679814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12679814</a>] [<a href="https://doi.org/10.1038/ng1141" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12679814">Meeks et al. (2003)</a> found that Nr0b1 is in fact required for testis differentiation. Sex reversal in the absence of Dax1 occurred after normal expression of Sry, suggesting that Sry and Dax1 are both required for normal testis determination. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9486644+12679814" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#30" class="mim-tip-reference" title="Nachtigal, M. W., Hirokawa, Y., Enyeart-VanHouten, D. L., Flanagan, J. N., Hammer, G. D., Ingraham, H. A. <strong>Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression.</strong> Cell 93: 445-454, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590178</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81172-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590178">Nachtigal et al. (1998)</a> showed that WT1(-KTS) (<a href="/entry/607102">607102</a>) isoforms associated and synergized with SF1 (<a href="/entry/184757">184757</a>) to promote mullerian inhibiting substance (MIS, or AMH; <a href="/entry/600957">600957</a>) expression. In contrast, WT1 missense mutations, associated with male pseudohermaphroditism in Denys-Drash syndrome (<a href="/entry/194080">194080</a>), failed to synergize with SF1. DAX1 antagonized synergy between SF1 and WT1, most likely through a direct interaction with SF1. <a href="#30" class="mim-tip-reference" title="Nachtigal, M. W., Hirokawa, Y., Enyeart-VanHouten, D. L., Flanagan, J. N., Hammer, G. D., Ingraham, H. A. <strong>Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression.</strong> Cell 93: 445-454, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590178</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81172-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590178">Nachtigal et al. (1998)</a> proposed that WT1 and DAX1 functionally oppose each other in testis development by modulating SF1-mediated transactivation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590178" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 coexpression in HeLa cells, <a href="#14" class="mim-tip-reference" title="Hossain, A., Li, C., Saunders, G. F. <strong>Generation of two distinct functional isoforms of dosage-sensitive sex reversal-adrenal hypoplasia congenita-critical region on the X chromosome gene 1 (DAX-1) by alternative splicing.</strong> Molec. Endocr. 18: 1428-1437, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15044589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15044589</a>] [<a href="https://doi.org/10.1210/me.2003-0176" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15044589">Hossain et al. (2004)</a> confirmed that DAX1 repressed SF1-mediated expression of reporter gene driven by the STAR promoter. DAX1-alpha relieved this repression in a dose-dependent manner. Similar results were obtained with a reporter construct containing the CYP17 (CYP17A1; <a href="/entry/609300">609300</a>) promoter. Like DAX1, in vitro-translated DAX1-alpha bound a hairpin DNA structure in the STAR promoter. SF1 coprecipitated with both DAX1 and DAX1-alpha, but only DAX1 bound the promoter region of Alien (COPS2; <a href="/entry/604508">604508</a>). <a href="#14" class="mim-tip-reference" title="Hossain, A., Li, C., Saunders, G. F. <strong>Generation of two distinct functional isoforms of dosage-sensitive sex reversal-adrenal hypoplasia congenita-critical region on the X chromosome gene 1 (DAX-1) by alternative splicing.</strong> Molec. Endocr. 18: 1428-1437, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15044589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15044589</a>] [<a href="https://doi.org/10.1210/me.2003-0176" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15044589">Hossain et al. (2004)</a> concluded that DAX1-alpha antagonizes the transcriptional repression activity of DAX1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15044589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using a yeast 2-hybrid system and transfected HEK293 cells, <a href="#15" class="mim-tip-reference" title="Iyer, A. K., Zhang, Y.-H., McCabe, E. R. B. <strong>Dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1) (NR0B1) and small heterodimer partner (SHP) (NR0B2) form homodimers individually, as well as DAX1-SHP heterodimers.</strong> Molec. Endocr. 20: 2326-2342, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16709599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16709599</a>] [<a href="https://doi.org/10.1210/me.2005-0383" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16709599">Iyer et al. (2006)</a> showed that DAX1 homodimerized. In HEK293 cells, homodimers were detected in both the nucleus and cytoplasm, and the homodimers dissociated upon heterodimerization with SF1 or ligand-activated ER-alpha (ESR1; <a href="/entry/133430">133430</a>). Homodimerization of DAX1 appeared to be mediated by antiparallel interaction between its N-terminal LxxLL motifs and C-terminal AF2 domain. SHP (NR0B2; <a href="/entry/604630">604630</a>) formed a similar antiparallel homodimer via its N-terminal LxxLL motifs and C-terminal AF2 domain, and DAX1 could form a heterodimer with SHP and also with DAX1A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16709599" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Iyer, A. K., Zhang, Y.-H., McCabe, E. R. B. <strong>LXXLL motifs and AF-2 domain mediate SHP (NR0B2) homodimerization and DAX1 (NR0B1)-DAX1A heterodimerization.</strong> Molec. Genet. Metab. 92: 151-159, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17686645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17686645</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17686645[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ymgme.2007.06.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17686645">Iyer et al. (2007)</a> showed that the DAX1-DAX1A interaction was mediated by the LxxLL domain of DAX1A and the AF2 domain of DAX1. DAX1A localized predominantly to the cytoplasm, whereas DAX1-DAX1A heterodimers localized to the nucleus, suggesting different functions for DAX1A in each compartment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17686645" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Kojima, Y., Sasaki, S., Hayashi, Y., Umemoto, Y., Morohashi, K.-I., Kohri, K. <strong>Role of transcription factors Ad4BP/SF-1 and DAX-1 in steroidogenesis and spermatogenesis in human testicular development and idiopathic azoospermia.</strong> Int. J. Urol. 13: 785-793, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16834661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16834661</a>] [<a href="https://doi.org/10.1111/j.1442-2042.2006.01403.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16834661">Kojima et al. (2006)</a> analyzed expression levels of NR0B1 mRNA in testicular tissue from 22 patients with nonobstructive azoospermia and detected NR0B1 in all specimens. Quantitative RT-PCR showed no significant relationship between the expression level of NR0B1 and serum testosterone concentration. However, the average expression levels of NR0B1 mRNA were significantly lower in patients with maturation arrest and Sertoli cell-only syndrome compared to patients with hypospermatogenesis or men with normal spermatogenesis and obstructive azoospermia, suggesting that the function of NR0B1 in Sertoli cells is required for normal spermatogenesis and fertility. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16834661" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Reviews</em></strong></p><p>
|
|
<a href="#33" class="mim-tip-reference" title="Niakan, K. K., McCabe, E. R. B. <strong>DAX1 origin, function, and novel role.</strong> Molec. Genet. Metab. 86: 70-83, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16146703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16146703</a>] [<a href="https://doi.org/10.1016/j.ymgme.2005.07.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16146703">Niakan and McCabe (2005)</a> reviewed the origin and function of DAX1 in human and mouse. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16146703" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Congenital Adrenal Hypoplasia</em></strong></p><p>
|
|
<a href="#29" class="mim-tip-reference" title="Muscatelli, F., Strom, T. M., Walker, A. P., Zanaria, E., Recan, D., Meindl, A., Bardoni, B., Guioli, S., Zehetner, G., Rabl, W., Schwarz, H. P., Kaplan, J.-C., Camerino, G., Meitinger, T., Monaco, A. P. <strong>Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.</strong> Nature 372: 672-676, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7990958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7990958</a>] [<a href="https://doi.org/10.1038/372672a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7990958">Muscatelli et al. (1994)</a> demonstrated that mutations in the DAX1 gene give rise to X-linked congenital adrenal hypoplasia with hypogonadotropic hypogonadism (AHC; <a href="/entry/300200">300200</a>). In 6 patients with AHC and 12 patients who had AHC with glycerol kinase deficiency (GKD; <a href="/entry/307030">307030</a>) or AHC-GKD with Duchenne muscular dystrophy (DMD) (see chromosome Xp21 deletion syndrome, <a href="/entry/300679">300679</a>), DAX1 was deleted. In 11 AHC families, and 1 sporadic case, point mutations were found in the coding region of the DAX1 gene (see, e.g., <a href="#0001">300473.0001</a>-<a href="#0005">300473.0005</a>). All AHC patients over 14 years of age and with only point mutations in DAX1 were also found to have hypogonadotropic hypogonadism, confirming that the DAX1 gene is responsible for both findings. However, in 4 sporadic cases and a single familial case of AHC, no point mutations were found, suggesting genetic heterogeneity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7990958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Guo, W., Burris, T. P., Zhang, Y.-H., Huang, B.-L., Mason, J., Copeland, K. C., Kupfer, S. R., Pagon, R. A., McCabe, E. R. B. <strong>Genomic sequence of the DAX1 gene: an orphan nuclear receptor responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.</strong> J. Clin. Endocr. Metab. 81: 2481-2486, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8675564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8675564</a>] [<a href="https://doi.org/10.1210/jcem.81.7.8675564" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8675564">Guo et al. (1996)</a> used SSCP analysis to identify 3 new DAX1 gene mutations as well as polymorphisms that may permit linkage analysis in families without identified mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8675564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Adrenal hypoplasia typically presents as adrenal insufficiency during infancy, whereas hypogonadotropic hypogonadism becomes evident in affected males who survive into childhood and approach puberty. <a href="#12" class="mim-tip-reference" title="Habiby, R. L., Boepple, P., Nachtigall, L., Sluss, P. M., Crowley, W. F., Jr., Jameson, J. L. <strong>Adrenal hypoplasia congenita with hypogonadotropic hypogonadism: evidence that DAX-1 mutations lead to combined hypothalamic and pituitary defects in gonadotropin production.</strong> J. Clin. Invest. 98: 1055-1062, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8770879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8770879</a>] [<a href="https://doi.org/10.1172/JCI118866" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8770879">Habiby et al. (1996)</a> identified mutations in the DAX1 gene in 2 affected members of 2 kindreds. Studies of baseline levels of luteinizing hormone (<a href="/entry/152780">152780</a>), FSHB (<a href="/entry/136530">136530</a>), and chorionic gonadotropin alpha (CGA; <a href="/entry/118850">118850</a>) demonstrated differences between the 2 families and suggested to <a href="#12" class="mim-tip-reference" title="Habiby, R. L., Boepple, P., Nachtigall, L., Sluss, P. M., Crowley, W. F., Jr., Jameson, J. L. <strong>Adrenal hypoplasia congenita with hypogonadotropic hypogonadism: evidence that DAX-1 mutations lead to combined hypothalamic and pituitary defects in gonadotropin production.</strong> J. Clin. Invest. 98: 1055-1062, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8770879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8770879</a>] [<a href="https://doi.org/10.1172/JCI118866" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8770879">Habiby et al. (1996)</a> that DAX1 mutations impair gonadotropin production by acting at both the hypothalamic and pituitary levels. <a href="#26" class="mim-tip-reference" title="McCabe, E. R. B. <strong>Sex and the single DAX1: too little is bad, but can we have too much? (Editorial)</strong> J. Clin. Invest. 98: 881-882, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8770856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8770856</a>] [<a href="https://doi.org/10.1172/JCI118868" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8770856">McCabe (1996)</a> agreed with these conclusions, noting that loss of DAX1 results in adrenal hypoplasia and hypogonadotropic hypogonadism, and increased DAX1 leads to dosage-sensitive sex reversal and a female phenotype or ambiguous genitalia in XY-genotypic males. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8770856+8770879" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#55" class="mim-tip-reference" title="Zhang, Y.-H., Guo, W., Wagner, R. L., Huang, B.-L., McCabe, L., Vilain, E., Burris, T. P., Anyane-Yeboa, K., Burghes, A. H. M., Chitayat, D., Chudley, A. E., Genel, M., and 12 others. <strong>DAX1 mutations map to putative structural domains in a deduced three-dimensional model.</strong> Am. J. Hum. Genet. 62: 855-864, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9529340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9529340</a>] [<a href="https://doi.org/10.1086/301782" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9529340">Zhang et al. (1998)</a> identified 14 new mutations in 17 families with AHC, bringing the total number of families with AHC studied to 48 and the number of reported mutations to 42; 1 family showed gonadal mosaicism. These mutations included 23 frameshift, 12 nonsense, and 6 missense mutations, and 1 single-codon deletion. They mapped 7 single amino acid changes to a homology model constructed by use of the 3-dimensional crystal structure of the thyroid hormone receptor (<a href="/entry/190160">190160</a>) and retinoid X receptor-alpha (<a href="/entry/180245">180245</a>). All single amino acid changes mapped to the C-terminal half of the DAX1 protein in the conserved hydrophobic core of the putative ligand-binding domain, and no affected residue was expected to interact directly with a ligand. <a href="#55" class="mim-tip-reference" title="Zhang, Y.-H., Guo, W., Wagner, R. L., Huang, B.-L., McCabe, L., Vilain, E., Burris, T. P., Anyane-Yeboa, K., Burghes, A. H. M., Chitayat, D., Chudley, A. E., Genel, M., and 12 others. <strong>DAX1 mutations map to putative structural domains in a deduced three-dimensional model.</strong> Am. J. Hum. Genet. 62: 855-864, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9529340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9529340</a>] [<a href="https://doi.org/10.1086/301782" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9529340">Zhang et al. (1998)</a> concluded that most genetic alterations in DAX1 are frameshift or nonsense mutations and speculated that the codon deletion and missense mutations give insight into the structure and function of DAX1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9529340" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#35" class="mim-tip-reference" title="Peter, M., Viemann, M., Partsch, C.-J., Sippell, W. G. <strong>Congenital adrenal hypoplasia: clinical spectrum, experience with hormonal diagnosis, and report on new point mutations of the DAX-1 gene.</strong> J. Clin. Endocr. Metab. 83: 2666-2674, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9709929/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9709929</a>] [<a href="https://doi.org/10.1210/jcem.83.8.5027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9709929">Peter et al. (1998)</a> studied 18 AHC boys from 16 families: 4 with AHC, GKD, and DMD; 2 with AHC and GKD; and 12 with AHC (5 young adults with hypogonadotropic hypogonadism). Most presented as neonates with salt wasting and hyperpigmentation. Aldosterone deficiency usually preceded cortisol deficiency, which explained why the patients more often presented with salt-wasting rather than with hypoglycemic symptoms. In samples from the 15 patients studied by molecular analysis of the DAX1 gene, large deletions were found in 6 patients, and point mutations in another 7. All of the point mutations identified encoded a nonfunctional, truncated DAX1 protein. Two brothers with primary adrenal insufficiency and histories strongly suggesting AHC had no mutation in the DAX1 gene, suggesting genetic heterogeneity for the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9709929" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#28" class="mim-tip-reference" title="Merke, D. P., Tajima, T., Baron, J., Cutler, G. B., Jr. <strong>Hypogonadotropic hypogonadism in a female caused by an X-linked recessive mutation in the DAX1 gene.</strong> New Eng. J. Med. 340: 1248-1252, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10210708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10210708</a>] [<a href="https://doi.org/10.1056/NEJM199904223401605" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10210708">Merke et al. (1999)</a> studied a family in which 2 males had a nonsense mutation in the DAX1 gene as the cause of congenital adrenal hypoplasia with gonadotropic hypogonadism. Their unaffected mother was heterozygous and their unaffected maternal grandfather was hemizygous for the nonsense mutation; the authors stated that the latter findings indicated a lack of penetrance of the mutation. The results of mutation analysis of DNA from urinary sediment were similar to those in leukocyte DNA. A maternal aunt, who had isolated hypogonadotropic hypogonadism, was homozygous for the mutation. This homozygosity was thought to have resulted from gene conversion, the nonreciprocal transfer of DNA from one parental allele to the other. This is a novel suggestion for manifestations in heterozygous females. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10210708" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#37" class="mim-tip-reference" title="Phelan, J. K., McCabe, E. R. B. <strong>Mutations in NR0B1 (DAX1) and NR5A1 (SF1) responsible for adrenal hypoplasia congenita.</strong> Hum. Mutat. 18: 472-487, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11748841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11748841</a>] [<a href="https://doi.org/10.1002/humu.1225" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11748841">Phelan and McCabe (2001)</a> presented a compendium of published NR0B1 mutations and polymorphisms, and discussed them in the context of known biology and clinical applicability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11748841" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Lehmann, S. G., Lalli, E., Sassone-Corsi, P. <strong>X-linked adrenal hypoplasia congenita is caused by abnormal nuclear localization of the DAX-1 protein.</strong> Proc. Nat. Acad. Sci. 99: 8225-8230, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12034880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12034880</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12034880[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.122044099" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12034880">Lehmann et al. (2002)</a> noted that all known DAX1 mutations found in AHC patients alter the C terminus of the protein, which shares similarity to the ligand-binding domain of nuclear hormone receptors and bears transcriptional repressor activity. This property is invariably impaired in DAX1 AHC mutants. <a href="#21" class="mim-tip-reference" title="Lehmann, S. G., Lalli, E., Sassone-Corsi, P. <strong>X-linked adrenal hypoplasia congenita is caused by abnormal nuclear localization of the DAX-1 protein.</strong> Proc. Nat. Acad. Sci. 99: 8225-8230, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12034880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12034880</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12034880[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.122044099" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12034880">Lehmann et al. (2002)</a> showed that the localization of DAX1 AHC mutant proteins is drastically shifted toward the cytoplasm, even if their nuclear localization signal, which resides in the N-terminal region of the protein, is intact. Cytoplasmic localization of DAX1 AHC mutants correlates with an impairment in their transcriptional repression activity. These results revealed a critical role of an intact C terminus in determining DAX1 subcellular localization and constituted an important example of a defect in human organogenesis caused by impaired nuclear localization of a transcription factor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12034880" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Lehmann, S. G., Wurtz, J.-M., Renaud, J.-P., Sassone-Corsi, P., Lalli, E. <strong>Structure-function analysis reveals the molecular determinants of the impaired biological function of DAX-1 mutants in AHC patients.</strong> Hum. Molec. Genet. 12: 1063-1072, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12700175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12700175</a>] [<a href="https://doi.org/10.1093/hmg/ddg108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12700175">Lehmann et al. (2003)</a> showed that several DAX1 AHC mutants had a misfolded conformation, which correlated with their cytoplasmic retention. Extensive structure-function analysis revealed that the chemical nature of amino acid residues at positions interrupted by AHC mutations and critical determinants in helix 12 affected DAX1 nuclear localization and transcriptional silencing. Mutations in a conserved putative corepressor binding surface had a negative effect upon DAX1 transcriptional repression only when they also affected protein expression levels. <a href="#22" class="mim-tip-reference" title="Lehmann, S. G., Wurtz, J.-M., Renaud, J.-P., Sassone-Corsi, P., Lalli, E. <strong>Structure-function analysis reveals the molecular determinants of the impaired biological function of DAX-1 mutants in AHC patients.</strong> Hum. Molec. Genet. 12: 1063-1072, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12700175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12700175</a>] [<a href="https://doi.org/10.1093/hmg/ddg108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12700175">Lehmann et al. (2003)</a> suggested that a folding defect underlies the impaired function of DAX1 missense mutants found in AHC/HHG patients, and that interactions with transcriptional cofactors different from known corepressors mediate DAX1 silencing properties. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12700175" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 male relatives with adrenal phenotypes ranging from adrenal crisis in infancy to asymptomatic adrenal insufficiency, <a href="#38" class="mim-tip-reference" title="Raffin-Sanson, M.-L., Oudet, B., Salenave, S., Brailly-Tabard, S., Pehuet, M., Christin-Maitre, S., Morel, Y., Young, J. <strong>A man with a DAX1/NR0B1 mutation, normal puberty, and an intact hypothalamic-pituitary-gonadal axis but deteriorating oligospermia during long-term follow-up.</strong> Europ. J. Endocr. 168: K45-K50, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23384712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23384712</a>] [<a href="https://doi.org/10.1530/EJE-12-1055" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23384712">Raffin-Sanson et al. (2013)</a> identified a trp39-to-ter mutation in NR0B1 (W39X; <a href="#0031">300473.0031</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23384712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>46,XY Sex Reversal</em></strong></p><p>
|
|
<a href="#4" class="mim-tip-reference" title="Bardoni, B., Zanaria, E., Guioli, S., Floridia, G., Worley, K. C., Tonini, G., Ferrante, E., Chiumello, G., McCabe, E. R. B., Fraccaro, M., Zuffardi, O., Camerino, G. <strong>A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal.</strong> Nature Genet. 7: 497-501, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951319/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951319</a>] [<a href="https://doi.org/10.1038/ng0894-497" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7951319">Bardoni et al. (1994)</a> studied 8 patients with duplications at chromosome Xp21, including 4 who had 46,XY sex reversal (SRXY2; <a href="/entry/300018">300018</a>) and 4 who were 46,XY phenotypic males. Breakpoint analysis identified an approximately 20-Mb region on Xp21.2-p22.1 that was duplicated only in the 46,XY females. Further analysis involving 1 additional 46,XY sex-reversed patient with a submicroscopic duplication on Xp defined a 160-kb critical region adjacent to the congenital adrenal hypoplasia locus (AHC; <a href="/entry/300200">300200</a>) that was exclusively duplicated in the patients with male-to-female sex reversal; the authors designated the locus DSS for 'dosage-sensitive sex reversal' (see <a href="#0014">300473.0014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951319" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Associations Pending Confirmation</em></strong></p><p>
|
|
For discussion of a possible association between mutation in the NR0B1 gene and a form of AHC involving isolated mineralocorticoid deficiency, see <a href="#0030">300473.0030</a>.</p><p><strong><em>Exclusion of DAX1 Mutations</em></strong></p><p>
|
|
<a href="#48" class="mim-tip-reference" title="Telvi, L., Ion, A., Carel, J.-C., Desguerre, I., Piraud, M., Boutin, A. M., Feingold, J., Ponsot, G., Fellous, M., McElreavey, K. <strong>A duplication of distal Xp associated with hypogonadotrophic hypogonadism, hypoplastic external genitalia, mental retardation, and multiple congenital abnormalities.</strong> J. Med. Genet. 33: 767-771, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8880579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8880579</a>] [<a href="https://doi.org/10.1136/jmg.33.9.767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8880579">Telvi et al. (1996)</a> reported GTD associated with mental retardation, facial dysmorphism, and hypoplastic external genitalia in an 18-year-old male with familial duplication of the segment Xp22.32-p22.11. Molecular analysis showed that the DAX1 gene was not involved in this duplication. Two sisters with the same inv dup(Xp) chromosome had short stature but were otherwise phenotypically normal. The abnormal X chromosome was late replicating in 96 to 98% of cells from the sisters. The authors discussed several possible explanations for the proband's phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8880579" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Achermann, J. C., Gu, W.-X., Kotlar, T. J., Meeks, J. J., Sabacan, L. P., Seminara, S. B., Habiby, R. L., Hindmarsh, P. C., Bick, D. P., Sherins, R. J., Crowley, W. F., Jr., Layman, L. C., Jameson, J. L. <strong>Mutational analysis of DAX1 in patients with hypogonadotropic hypogonadism or pubertal delay.</strong> J. Clin. Endocr. Metab. 84: 4497-4500, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10599708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10599708</a>] [<a href="https://doi.org/10.1210/jcem.84.12.6269" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10599708">Achermann et al. (1999)</a> hypothesized that DAX1 might be a candidate gene in patients with idiopathic sporadic or familial HHG or constitutional delay of puberty. They performed direct sequencing of the DAX1 gene in 106 patients, including 85 (80 men and 5 women) with sporadic HHG or constitutional delay of puberty and patients from 21 kindreds with familial forms of these disorders. No DAX1 mutations were found in these groups of patients, although silent single nucleotide polymorphisms were identified. The authors concluded that mutations in DAX1 are unlikely to be a common cause of HHG or pubertal delay in the absence of a concomitant history of adrenal insufficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10599708" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#6" class="mim-tip-reference" title="Calvo, R. M., Asuncion, M., Telleria, D., Sancho, J., San Millan, J. L., Escobar-Morreale, H. F. <strong>Screening for mutations in the steroidogenic acute regulatory protein and steroidogenic factor-1 genes, and in CYP11A and dosage-sensitive sex reversal-adrenal hypoplasia gene on the X chromosome, gene-1 (DAX-1), in hyperandrogenic hirsute women.</strong> J. Clin. Endocr. Metab. 86: 1746-1749, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11297612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11297612</a>] [<a href="https://doi.org/10.1210/jcem.86.4.7424" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11297612">Calvo et al. (2001)</a> used heteroduplex analysis to screen the genes encoding STAR, SF1, DAX1, and CYP11A (<a href="/entry/118485">118485</a>) for mutations in genomic DNA from 19 women presenting with hirsutism and increased serum androgen levels. Analysis of DAX1 showed no variant in any of the women studied. The authors concluded that mutations in STAR, SF1, CYP11A, and DAX1 are seldom found in hirsute patients and do not explain the steroidogenic abnormalities found in these women. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11297612" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Lin, L., Gu, W.-X., Ozisik, G., To, W. S., Owen, C. J., Jameson, J. L., Achermann, J. C. <strong>Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (NR5A1) in children and adults with primary adrenal failure: ten years' experience.</strong> J. Clin. Endocr. Metab. 91: 3048-3054, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16684822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16684822</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16684822[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/10.1210/jc.2006-0603" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16684822">Lin et al. (2006)</a> studied the prevalence of DAX1 and SF1 mutations in 117 children and adults with primary adrenal failure of unknown etiology (i.e., not caused by congenital adrenal hyperplasia, adrenoleukodystrophy, or autoimmune disease). DAX1 mutations were found in 58% (37 of 64) of 46,XY phenotypic boys referred with adrenal hypoplasia and in all boys (8 of 8) with hypogonadotropic hypogonadism and a family history suggestive of adrenal failure in males. SF1 mutations causing adrenal failure were found in only 2 patients with 46,XY gonadal dysgenesis. No DAX1 or SF1 mutations were identified in the adult-onset group. <a href="#23" class="mim-tip-reference" title="Lin, L., Gu, W.-X., Ozisik, G., To, W. S., Owen, C. J., Jameson, J. L., Achermann, J. C. <strong>Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (NR5A1) in children and adults with primary adrenal failure: ten years' experience.</strong> J. Clin. Endocr. Metab. 91: 3048-3054, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16684822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16684822</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16684822[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/10.1210/jc.2006-0603" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16684822">Lin et al. (2006)</a> concluded that DAX1 mutations are a relatively frequent cause of adrenal failure in this group of boys, whereas SF1 mutations causing adrenal failure in humans are rare and are more likely to be associated with significant underandrogenization and gonadal dysfunction in 46,XY individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16684822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>In the mouse, <a href="#52" class="mim-tip-reference" title="Yu, R. N., Ito, M., Saunders, T. L., Camper, S. A., Jameson, J. L. <strong>Role of Ahch in gonadal development and gametogenesis.</strong> Nature Genet. 20: 353-357, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9843206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9843206</a>] [<a href="https://doi.org/10.1038/3822" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9843206">Yu et al. (1998)</a> disrupted the Ahch gene to generate a mouse model of congenital adrenal hypoplasia with hypogonadotropic hypogonadism that allowed the function of Ahch to be examined in both males and females. Though Ahch had been postulated to function as an ovarian determination gene, the loss of Ahch function in females did not affect ovarian development or fertility. Instead, Ahch was essential for the maintenance of spermatogenesis. Lack of Ahch caused progressive degeneration of the testicular germinal epithelium independent of abnormalities in gonadotropin and testosterone production and resulted in male sterility. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9843206" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#17" class="mim-tip-reference" title="Kang, Y., Zheng, B., Shen, B., Chen, Y., Wang, L., Wang, J., Niu, Y., Cui, Y., Zhou, J., Wang, H., Guo, X., Hu, B., Zhou, Q., Sha, J., Ji, W., Huang, X. <strong>CRISPR/Cas9-mediated Dax1 knockout in the monkey recapitulates human AHC-HH.</strong> Hum. Molec. Genet. 24: 7255-7264, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26464492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26464492</a>] [<a href="https://doi.org/10.1093/hmg/ddv425" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26464492">Kang et al. (2015)</a> used CRISPR/Cas9 genome engineering to mutate Dax1 in cynomolgus monkey. They obtained no live offspring with Dax1 mutations following embryo transfer, but several fetuses showed extensive Dax1 modifications, including a male fetus with targeted mutations in Dax1 in most somatic tissues and gonad. Testis of the Dax1-deficient fetus was grossly normal, but it had altered ultrastructural morphology and expansion of blood vessels. Absence of Dax1 did not alter Sertoli cell fate, testis cords were well organized, and tubular structure remained intact, but with reduced number of germ cells. Dax1-deficient testis showed normal expression of Amh, Sox9 (<a href="/entry/608160">608160</a>), and Wt1, but expression of the Wnt signaling protein beta-catenin (CTNNB1; <a href="/entry/116806">116806</a>) was upregulated in interstitial cells, as was Vegf (VEGFA; <a href="/entry/192240">192240</a>) content. Adrenal gland of the Dax1-deficient fetus showed substantial enlargement of the fetal zone. Dax1 deficiency did not cause any apparent defects in other tissues or organs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26464492" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>31 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/300473" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=300473[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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, GLN283TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894890 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894890;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=rs104894890" 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=rs104894890" 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=RCV000011696" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011696" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011696</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 44-year-old man who had AHC with hypogonadotropic hypogonadism (<a href="/entry/300200">300200</a>), <a href="#29" class="mim-tip-reference" title="Muscatelli, F., Strom, T. M., Walker, A. P., Zanaria, E., Recan, D., Meindl, A., Bardoni, B., Guioli, S., Zehetner, G., Rabl, W., Schwarz, H. P., Kaplan, J.-C., Camerino, G., Meitinger, T., Monaco, A. P. <strong>Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.</strong> Nature 372: 672-676, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7990958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7990958</a>] [<a href="https://doi.org/10.1038/372672a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7990958">Muscatelli et al. (1994)</a> identified a nonsense mutation in the NR0B1 gene involving gln283 (Q283X) and leading to suppression of a PvuII site. Age at onset of the disorder was 10 days of life. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7990958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, TRP369TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894886 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894886;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=rs104894886" 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=rs104894886" 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=RCV000011697" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011697" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011697</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with AHC (<a href="/entry/300200">300200</a>) and bilateral cryptorchidism, <a href="#29" class="mim-tip-reference" title="Muscatelli, F., Strom, T. M., Walker, A. P., Zanaria, E., Recan, D., Meindl, A., Bardoni, B., Guioli, S., Zehetner, G., Rabl, W., Schwarz, H. P., Kaplan, J.-C., Camerino, G., Meitinger, T., Monaco, A. P. <strong>Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.</strong> Nature 372: 672-676, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7990958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7990958</a>] [<a href="https://doi.org/10.1038/372672a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7990958">Muscatelli et al. (1994)</a> identified a W369X nonsense mutation in the NR0B1 gene. Age at onset of the disorder was 17 days of life. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7990958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, LEU263TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894887 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894887;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=rs104894887" 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=rs104894887" 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=RCV000011698" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011698" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011698</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient who had AHC with hypogonadotropic hypogonadism (<a href="/entry/300200">300200</a>), <a href="#29" class="mim-tip-reference" title="Muscatelli, F., Strom, T. M., Walker, A. P., Zanaria, E., Recan, D., Meindl, A., Bardoni, B., Guioli, S., Zehetner, G., Rabl, W., Schwarz, H. P., Kaplan, J.-C., Camerino, G., Meitinger, T., Monaco, A. P. <strong>Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.</strong> Nature 372: 672-676, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7990958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7990958</a>] [<a href="https://doi.org/10.1038/372672a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7990958">Muscatelli et al. (1994)</a> identified a L263X nonsense mutation in the NR0B1 gene, which created a BstUI site. Age of AHC onset was 8 days of life, and age of HHG onset was before 14 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7990958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, ARG267PRO
|
|
</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> rs104894888 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894888;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/rs104894888?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=rs104894888" 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=rs104894888" 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=RCV000011699 OR RCV001851797" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011699, RCV001851797" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011699...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers with AHC with hypogonadotropic hypogonadism (<a href="/entry/300200">300200</a>), <a href="#29" class="mim-tip-reference" title="Muscatelli, F., Strom, T. M., Walker, A. P., Zanaria, E., Recan, D., Meindl, A., Bardoni, B., Guioli, S., Zehetner, G., Rabl, W., Schwarz, H. P., Kaplan, J.-C., Camerino, G., Meitinger, T., Monaco, A. P. <strong>Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.</strong> Nature 372: 672-676, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7990958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7990958</a>] [<a href="https://doi.org/10.1038/372672a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7990958">Muscatelli et al. (1994)</a> identified a 1034G-A transition in the NR0B1 gene, which was predicted to generate an arg267-to-pro (R267P) substitution, and resulted in suppression of a CfoI site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7990958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#19" class="mim-tip-reference" title="Lalli, E., Bardoni, B., Zazopoulos, E., Wurtz, J.-M., Strom, T. M., Moras, D., Sassone-Corsi, P. <strong>A transcriptional silencing domain in DAX-1 whose mutation causes adrenal hypoplasia congenita.</strong> Molec. Endocr. 11: 1950-1960, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9415399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9415399</a>] [<a href="https://doi.org/10.1210/mend.11.13.0038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9415399">Lalli et al. (1997)</a> found that 2 mutations in the DAX1 gene, R267P and deletion of V269, impair transcriptional silencing of the STAR promoter, suggesting that loss of the functional repression plays a role in the pathogenesis of AHC. (See also <a href="#20" class="mim-tip-reference" title="Lalli, E., Ohe, K., Hindelang, C., Sassone-Corsi, P. <strong>Orphan receptor DAX-1 is a shuttling RNA binding protein associated with polyribosomes via mRNA.</strong> Molec. Cell. Biol. 20: 4910-4921, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10848616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10848616</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10848616[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.20.13.4910-4921.2000" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10848616">Lalli et al. (2000)</a> and <a href="#0008">300473.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9415399+10848616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, TRP235TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894889 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894889;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=rs104894889" 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=rs104894889" 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=RCV000011700" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011700" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011700</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male patient who had AHC with hypogonadotropic hypogonadism (<a href="/entry/300200">300200</a>), <a href="#29" class="mim-tip-reference" title="Muscatelli, F., Strom, T. M., Walker, A. P., Zanaria, E., Recan, D., Meindl, A., Bardoni, B., Guioli, S., Zehetner, G., Rabl, W., Schwarz, H. P., Kaplan, J.-C., Camerino, G., Meitinger, T., Monaco, A. P. <strong>Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.</strong> Nature 372: 672-676, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7990958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7990958</a>] [<a href="https://doi.org/10.1038/372672a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7990958">Muscatelli et al. (1994)</a> observed a G-to-A transition in the NR0B1 gene, resulting in a nonsense mutation at codon 235 (trp235-to-ter; W235X), creating a MaeI restriction site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7990958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, TRP171TER
|
|
</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> rs104894891 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894891;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/rs104894891?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=rs104894891" 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=rs104894891" 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">rs104894893 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894893;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=rs104894893" 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=rs104894893" 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=RCV000011701" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011701" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011701</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese male patient, originally reported at 17 years of age by <a href="#46" class="mim-tip-reference" title="Takayanagi, R., Okabe, T., Sakai, O., Nawata, H., Kato, K., Ibayashi, H. <strong>A case of congenital adrenal hypoplasia and hypogonadism.</strong> Horumon To Rinsho 40: 81-84, 1992."None>Takayanagi et al. (1992)</a>, who had AHC with hypogonadotropic hypogonadism (<a href="/entry/300200">300200</a>) and whose brother and 2 maternal uncles had died in infancy or early childhood of hypovolemic shock, <a href="#51" class="mim-tip-reference" title="Yanase, T., Takayanagi, R., Oba, K., Nishi, Y., Ohe, K., Nawata, H. <strong>New mutations of DAX-1 genes in two Japanese patients with X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism.</strong> J. Clin. Endocr. Metab. 81: 530-535, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8636263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8636263</a>] [<a href="https://doi.org/10.1210/jcem.81.2.8636263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8636263">Yanase et al. (1996)</a> found a G-to-A transition in the NR0B1 gene, resulting in a nonsense mutation at codon 171 (trp171-to-ter; W171X). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8636263" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, 1-BP DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011702" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011702" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011702</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 20-year-old Japanese man who had an apparently sporadic case of AHC with hypogonadotropic hypogonadism (<a href="/entry/300200">300200</a>), <a href="#51" class="mim-tip-reference" title="Yanase, T., Takayanagi, R., Oba, K., Nishi, Y., Ohe, K., Nawata, H. <strong>New mutations of DAX-1 genes in two Japanese patients with X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism.</strong> J. Clin. Endocr. Metab. 81: 530-535, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8636263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8636263</a>] [<a href="https://doi.org/10.1210/jcem.81.2.8636263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8636263">Yanase et al. (1996)</a> identified a 1-bp deletion (delT) in codon 280, leading to a frameshift and a premature stop at codon 371. The mutation created a new MspI restriction site which was absent in the PCR products of both parents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8636263" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, ASN440ILE
|
|
</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> rs28935481 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28935481;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/rs28935481?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=rs28935481" 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=rs28935481" 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=RCV000011704" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011704" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011704</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 male patients with AHC (<a href="/entry/300200">300200</a>) from the Greenlandic family originally reported by <a href="#36" class="mim-tip-reference" title="Petersen, K. E., Bille, T., Jacobsen, B. B., Iversen, T. <strong>X-linked congenital adrenal hypoplasia: a study of five generations of a Greenlandic family.</strong> Acta Paediat. Scand. 71: 947-951, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6891556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6891556</a>] [<a href="https://doi.org/10.1111/j.1651-2227.1982.tb09554.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6891556">Petersen et al. (1982)</a>, <a href="#41" class="mim-tip-reference" title="Schwartz, M., Blichfeldt, S., Muller, J. <strong>X-linked adrenal hypoplasia in a large Greenlandic family. Detection of a missense mutation (N4401) in the DAX-1 gene; implication for genetic counselling and carrier diagnosis.</strong> Hum. Genet. 99: 83-87, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9003500/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9003500</a>] [<a href="https://doi.org/10.1007/s004390050316" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9003500">Schwartz et al. (1997)</a> identified a 1553A-T transversion in the NR0B1 gene, resulting in an asn440-to-ile (N440I) substitution. The substitution represented change from a polar amino acid to a nonpolar amino acid. Both patients who had reached the age of puberty exhibited hypogonadotropic hypogonadism. The authors noted that among 33 female relatives at risk for the mutation, they identified 10 as carriers and excluded 23 from being carriers, information important for genetic counseling. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6891556+9003500" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Lalli, E., Ohe, K., Hindelang, C., Sassone-Corsi, P. <strong>Orphan receptor DAX-1 is a shuttling RNA binding protein associated with polyribosomes via mRNA.</strong> Molec. Cell. Biol. 20: 4910-4921, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10848616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10848616</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10848616[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.20.13.4910-4921.2000" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10848616">Lalli et al. (2000)</a> determined that the N440I mutation results in impaired RNA-binding activity of the DAX1 protein (see also <a href="#19" class="mim-tip-reference" title="Lalli, E., Bardoni, B., Zazopoulos, E., Wurtz, J.-M., Strom, T. M., Moras, D., Sassone-Corsi, P. <strong>A transcriptional silencing domain in DAX-1 whose mutation causes adrenal hypoplasia congenita.</strong> Molec. Endocr. 11: 1950-1960, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9415399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9415399</a>] [<a href="https://doi.org/10.1210/mend.11.13.0038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9415399">Lalli et al., 1997</a> and <a href="#0004">300473.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9415399+10848616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, GLN395TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894894 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894894;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=rs104894894" 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=rs104894894" 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=RCV000011705 OR RCV000481802" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011705, RCV000481802" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011705...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#32" class="mim-tip-reference" title="Nakae, J., Tajima, T., Kusuda, S., Kohda, N., Okabe, T., Shinohara, N., Kato, M., Murashita, M., Mukai, T., Imanaka, K., Fujieda, K. <strong>Truncation at the C-terminus of the DAX-1 protein impairs its biological actions in patients with X-linked adrenal hypoplasia congenita.</strong> J. Clin. Endocr. Metab. 81: 3680-3685, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8855822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8855822</a>] [<a href="https://doi.org/10.1210/jcem.81.10.8855822" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8855822">Nakae et al. (1996)</a> characterized the DAX1 gene from 6 patients, including 2 sibs, with AHC (<a href="/entry/300200">300200</a>), and found 5 novel mutations including 3 nonsense and 2 frameshift mutations. The nonsense mutations were a C-to-T transition (gln395-to-ter; Q395X), a C-to-G transversion (tyr271-to-ter; Y271X; <a href="#0010">300473.0010</a>), and a C-to-A transversion (tyr91-to-ter; Y91X; <a href="#0011">300473.0011</a>). The Y91X mutation was found in 2 sibs. The frameshift mutations were a 2-bp deletion (1610delAT) and a 1-bp (G) insertion resulting in a premature stop at codon 462 (<a href="#0012">300473.0012</a>), and a 1-bp deletion (1169delC), resulting in a frameshift which caused a premature stop codon at position 371 (<a href="#0013">300473.0013</a>). A 21-year-old male patient in whom the Q395X mutation was identified had hypogonadotropic hypogonadism; the other 5 patients were prepubertal. All mutated NR0B1 proteins had truncated C-terminal domains, suggesting that these 5 mutations cause AHC and that the C terminus of the DAX1 protein, especially the terminal 11 amino acids, is necessary for normal adrenal cortical embryogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8855822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, TYR271TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894895 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894895;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=rs104894895" 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=rs104894895" 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=RCV000011706" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011706" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011706</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See <a href="#0009">300473.0009</a> and <a href="#32" class="mim-tip-reference" title="Nakae, J., Tajima, T., Kusuda, S., Kohda, N., Okabe, T., Shinohara, N., Kato, M., Murashita, M., Mukai, T., Imanaka, K., Fujieda, K. <strong>Truncation at the C-terminus of the DAX-1 protein impairs its biological actions in patients with X-linked adrenal hypoplasia congenita.</strong> J. Clin. Endocr. Metab. 81: 3680-3685, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8855822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8855822</a>] [<a href="https://doi.org/10.1210/jcem.81.10.8855822" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8855822">Nakae et al. (1996)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8855822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, TYR91TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894892 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894892;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=rs104894892" 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=rs104894892" 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=RCV000011703 OR RCV000413730" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011703, RCV000413730" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011703...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See <a href="#0009">300473.0009</a> and <a href="#32" class="mim-tip-reference" title="Nakae, J., Tajima, T., Kusuda, S., Kohda, N., Okabe, T., Shinohara, N., Kato, M., Murashita, M., Mukai, T., Imanaka, K., Fujieda, K. <strong>Truncation at the C-terminus of the DAX-1 protein impairs its biological actions in patients with X-linked adrenal hypoplasia congenita.</strong> J. Clin. Endocr. Metab. 81: 3680-3685, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8855822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8855822</a>] [<a href="https://doi.org/10.1210/jcem.81.10.8855822" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8855822">Nakae et al. (1996)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8855822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, 2-BP DEL, 1610AG, AND 1-BP INS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011707" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011707" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011707</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See <a href="#0009">300473.0009</a> and <a href="#32" class="mim-tip-reference" title="Nakae, J., Tajima, T., Kusuda, S., Kohda, N., Okabe, T., Shinohara, N., Kato, M., Murashita, M., Mukai, T., Imanaka, K., Fujieda, K. <strong>Truncation at the C-terminus of the DAX-1 protein impairs its biological actions in patients with X-linked adrenal hypoplasia congenita.</strong> J. Clin. Endocr. Metab. 81: 3680-3685, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8855822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8855822</a>] [<a href="https://doi.org/10.1210/jcem.81.10.8855822" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8855822">Nakae et al. (1996)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8855822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, 1-BP DEL, 1169C
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011708" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011708" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011708</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See <a href="#0009">300473.0009</a> and <a href="#32" class="mim-tip-reference" title="Nakae, J., Tajima, T., Kusuda, S., Kohda, N., Okabe, T., Shinohara, N., Kato, M., Murashita, M., Mukai, T., Imanaka, K., Fujieda, K. <strong>Truncation at the C-terminus of the DAX-1 protein impairs its biological actions in patients with X-linked adrenal hypoplasia congenita.</strong> J. Clin. Endocr. Metab. 81: 3680-3685, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8855822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8855822</a>] [<a href="https://doi.org/10.1210/jcem.81.10.8855822" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8855822">Nakae et al. (1996)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8855822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 46,XY SEX REVERSAL 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, DUP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011709" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011709" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011709</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>XY individuals with a duplication of part of the short arm of the X chromosome and an intact SRY gene show male-to-female sex reversal (SRXY2; <a href="/entry/300018">300018</a>). The single X chromosome in these individuals does not undergo X-chromosome inactivation; therefore, these individuals presumably carry 2 active copies of genes, including the NR0B1 gene, in the duplicated region. Individuals with deletion of this region develop as males. Genes within the DSS region are, therefore, not essential for testis development, but, when present in a double dose, interfere with testis formation (<a href="#43" class="mim-tip-reference" title="Swain, A., Narvaez, V., Burgoyne, P., Camerino, G., Lovell-Badge, R. <strong>Dax1 antagonizes Sry action in mammalian sex determination.</strong> Nature 391: 761-767, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9486644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9486644</a>] [<a href="https://doi.org/10.1038/35799" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9486644">Swain et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9486644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, 2-BP DEL, 388AG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2147007424 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2147007424;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=rs2147007424" 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=rs2147007424" 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=RCV001837630 OR RCV002280832" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001837630, RCV002280832" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001837630...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#31" class="mim-tip-reference" title="Nakae, J., Abe, S., Tajima, T., Shinohara, N., Murashita, M., Igarashi, Y., Kusuda, S., Suzuki, J., Fujieda, K. <strong>Three novel mutations and a de novo deletion mutation of the DAX-1 gene in patients with X-linked adrenal hypoplasia congenita.</strong> J. Clin. Endocr. Metab. 82: 3835-3841, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9360549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9360549</a>] [<a href="https://doi.org/10.1210/jcem.82.11.4342" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9360549">Nakae et al. (1997)</a> characterized the NR0B1 gene from 7 patients in 6 kindreds with AHC (<a href="/entry/300200">300200</a>) and identified 1 frameshift mutation, 2 missense mutations (see <a href="#0016">300473.0016</a> and <a href="#0017">300473.0017</a>), and 3 deletion mutations (see <a href="#0018">300473.0018</a>) in the NR0B1 gene. The frameshift mutation, found in a 26-year-old male patient who had AHC with hypogonadotropic hypogonadism, was a 2-bp deletion (388delAG) resulting in a premature stop codon at position 70. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9360549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, LYS382ASN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894896 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894896;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=rs104894896" 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=rs104894896" 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=RCV000011711" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011711" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011711</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 15-year-old male patient who had AHC with hypogonadotropic hypogonadism (<a href="/entry/300200">300200</a>), <a href="#31" class="mim-tip-reference" title="Nakae, J., Abe, S., Tajima, T., Shinohara, N., Murashita, M., Igarashi, Y., Kusuda, S., Suzuki, J., Fujieda, K. <strong>Three novel mutations and a de novo deletion mutation of the DAX-1 gene in patients with X-linked adrenal hypoplasia congenita.</strong> J. Clin. Endocr. Metab. 82: 3835-3841, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9360549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9360549</a>] [<a href="https://doi.org/10.1210/jcem.82.11.4342" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9360549">Nakae et al. (1997)</a> identified a 1380G-T transversion in the NR0B1 gene, resulting in a lys382-to-asn (L382N) substitution. Lys382 is highly conserved among other related orphan nuclear receptor superfamily members. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9360549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, TRP291CYS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28935482 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28935482;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=rs28935482" 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=rs28935482" 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=RCV000011712" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011712" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011712</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a pair of prepubertal sibs with AHC (<a href="/entry/300200">300200</a>), <a href="#31" class="mim-tip-reference" title="Nakae, J., Abe, S., Tajima, T., Shinohara, N., Murashita, M., Igarashi, Y., Kusuda, S., Suzuki, J., Fujieda, K. <strong>Three novel mutations and a de novo deletion mutation of the DAX-1 gene in patients with X-linked adrenal hypoplasia congenita.</strong> J. Clin. Endocr. Metab. 82: 3835-3841, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9360549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9360549</a>] [<a href="https://doi.org/10.1210/jcem.82.11.4342" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9360549">Nakae et al. (1997)</a> identified a 1107G-C transversion in the NR0B1 gene, resulting in a trp291-to-cys (W291C) substitution. Trp291 is highly conserved among other related orphan nuclear receptor superfamily members. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9360549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011713" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011713" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011713</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By Southern blotting and PCR of a GGAA tetranucleotide tandem repeat, <a href="#31" class="mim-tip-reference" title="Nakae, J., Abe, S., Tajima, T., Shinohara, N., Murashita, M., Igarashi, Y., Kusuda, S., Suzuki, J., Fujieda, K. <strong>Three novel mutations and a de novo deletion mutation of the DAX-1 gene in patients with X-linked adrenal hypoplasia congenita.</strong> J. Clin. Endocr. Metab. 82: 3835-3841, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9360549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9360549</a>] [<a href="https://doi.org/10.1210/jcem.82.11.4342" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9360549">Nakae et al. (1997)</a> detected deletions in the NR0B1 gene of 3 unrelated prepubertal patients with AHC (<a href="/entry/300200">300200</a>). The extents of the deletions were not determined. In 2 of the patients, the deletion was familial; in the third, it was de novo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9360549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, 4-BP DEL, NT1464
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1569268070 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569268070;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=rs1569268070" 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=rs1569268070" 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=RCV000011714 OR RCV002512973" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011714, RCV002512973" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011714...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 42-year-old patient who had congenital adrenal hypoplasia with hypogonadotropic hypogonadism (<a href="/entry/300200">300200</a>), <a href="#50" class="mim-tip-reference" title="Wang, J., Killinger, D. W., Hegele, R. A. <strong>A microdeletion within DAX-1 in X-linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism.</strong> J. Investig. Med. 47: 232-235, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10361383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10361383</a>]" pmid="10361383">Wang et al. (1999)</a> identified a 4-bp deletion (1464delACTC) in the second exon of the NR0B1 sequence, which caused a frameshift and predicted a premature stop codon at amino acid 416. The diagnosis of AHC and HHG had been made at 2 weeks of age when he presented to the Hospital for Sick Children in Toronto with vomiting, loose stools, and failure to thrive. He was treated with intramuscular deoxycortisone acetate (DOCA) and discharged with 2 subcutaneous DOCA pellets. Prednisone was started with added salt at the age of 23 months. He had been maintained on glucocorticoids since that time. At age 15 he developed a slipped left femoral epiphysis, which was treated surgically. His bone age at that time was 11 years. He had no secondary sexual development when studied at the age of 17 years and was started on testosterone. No other family members were affected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10361383" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, ILE439SER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894897 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894897;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=rs104894897" 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=rs104894897" 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=RCV000011716" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011716" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011716</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a man who presented with apparently isolated adrenal insufficiency at 28 years of age, later confirmed as AHC (<a href="/entry/300200">300200</a>), <a href="#45" class="mim-tip-reference" title="Tabarin, A., Achermann, J. C., Recan, D., Bex, V., Bertagna, X., Christin-Maitre, S., Ito, M., Jameson, J. L., Bouchard, P. <strong>A novel mutation in DAX1 causes delayed-onset adrenal insufficiency and incomplete hypogonadotropic hypogonadism.</strong> J. Clin. Invest. 105: 321-328, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10675358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10675358</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10675358[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI7212" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10675358">Tabarin et al. (2000)</a> found a missense mutation, ile439-to-ser (I439S), in the DAX1 gene. Physical examination revealed partial pubertal development and undiagnosed incomplete hypogonadotropic hypogonadism. Gonadotropin therapy did not improve his marked oligospermia, suggesting a concomitant primary testicular abnormality. The patient's complaint was fatigue for 5 years. During the year before study, the patient noted additional symptoms, such as episodes of nausea, abdominal pain, orthostatic dizziness, and loss of 4.5 kg of body weight. His height and weight were 171 cm and 58 kg, respectively, and his blood pressure was 100/60 mm Hg while supine. On physical examination, moderate and diffuse increased skin pigmentation was noted, with a few hyperpigmented macules on the lips. Facial, thoracic, and pubic hair (Tanner stage 3) were sparse, with a gynecoid distribution of subcutaneous fat. There was no gynecomastia. Penile length was normal, but testicular volume was low (6 ml bilaterally). The patient stated that puberty had occurred at the age of approximately 16. He described impaired libido and infrequent erections. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10675358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#45" class="mim-tip-reference" title="Tabarin, A., Achermann, J. C., Recan, D., Bex, V., Bertagna, X., Christin-Maitre, S., Ito, M., Jameson, J. L., Bouchard, P. <strong>A novel mutation in DAX1 causes delayed-onset adrenal insufficiency and incomplete hypogonadotropic hypogonadism.</strong> J. Clin. Invest. 105: 321-328, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10675358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10675358</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10675358[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI7212" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10675358">Tabarin et al. (2000)</a> studied the mutant I439S protein for its ability to function as a transcriptional repressor of target genes. Consistent with the patient's mild clinical phenotype, the I439S mutation conferred intermediate levels of repressor activity of DAX1 when compared with mutations associated with classic AHC. This unique case extended the clinical spectrum of AHC to include delayed-onset primary adrenal insufficiency in adulthood and milder forms of HHG. In accordance with findings in Ahch(Dax1) knockout mice, the clinical features in this patient suggested that DAX1 function is required for spermatogenesis in humans, independent of its known effects on gonadotropin production. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10675358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, TYR197TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894898 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894898;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=rs104894898" 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=rs104894898" 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=RCV000011715" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011715" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011715</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#7" class="mim-tip-reference" title="Caron, P., Imbeaud, S., Bennet, A., Plantavid, M., Camerino, G., Rochiccioli, P. <strong>Combined hypothalamic-pituitary-gonadal defect in a hypogonadic man with a novel mutation in the DAX-1 gene.</strong> J. Clin. Endocr. Metab. 84: 3563-3569, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10522996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10522996</a>] [<a href="https://doi.org/10.1210/jcem.84.10.6030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10522996">Caron et al. (1999)</a> studied a 20-year-old male patient who had congenital adrenal hypoplasia with hypogonadotropic hypogonadism (<a href="/entry/300200">300200</a>) due to an 825C-A transversion in the NR0B1 gene, resulting in a tyr197-to-ter (Y197X) substitution. The same mutation was detected in the patient's affected first cousin and in heterozygous state in their carrier mothers. The patient had had acute adrenal insufficiency at the age of 2.5 years, bilateral cryptorchidism corrected surgically at the age of 12 years, and failure of spontaneous puberty. Plasma testosterone was undetectable and gonadotropin levels were low and not stimulated after intravenous injection of 100 microg gonadotropin-releasing hormone (GNRH; see <a href="/entry/152760">152760</a>). The endogenous LH secretory pattern was apulsatile, whereas free alpha-subunit levels depicted erratic pulses, suggesting an incomplete deficiency of hypothalamic GnRH secretion. The authors concluded that the hypogonadism was due to a combined hypothalamic-pituitary-gonadal defect and implied that the NR0B1 gene may play a critical role in human testicular function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10522996" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, 1-BP DEL, 501A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1569268976 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569268976;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=rs1569268976" 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=rs1569268976" 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=RCV000011717 OR RCV002280091 OR RCV003764555" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011717, RCV002280091, RCV003764555" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011717...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#42" class="mim-tip-reference" title="Seminara, S. B., Achermann, J. C., Genel, M., Jameson, J. L., Crowley, W. F., Jr. <strong>X-linked adrenal hypoplasia congenita: a mutation in DAX1 expands the phenotypic spectrum in males and females.</strong> J. Clin. Endocr. Metab. 84: 4501-4509, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10599709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10599709</a>] [<a href="https://doi.org/10.1210/jcem.84.12.6172" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10599709">Seminara et al. (1999)</a> studied an extended kindred with adrenal hypoplasia congenita with hypogonadotropic hypogonadism (<a href="/entry/300200">300200</a>) in which 2 males (the proband and his nephew) were affected with a nucleotide deletion (501delA) in the DAX1 gene. The proband's mother, sister, and niece were heterozygous for this frameshift mutation. At age 27 years, after 7 years of low dose hCG therapy, the proband underwent a testicular biopsy revealing rare spermatogonia and Leydig cell hyperplasia. Despite steadily progressive doses of hCG and Pergonal administered over a 3-year period, the proband remained azoospermic. The proband's mother, sister (obligate carrier), and niece all had a history of delayed puberty, with menarche occurring at ages 17-18 years. The authors concluded that (1) affected males with AHC/HHG may have an intrinsic defect in spermatogenesis that is not responsive to gonadotropin therapy; (2) female carriers of DAX1 mutations may express the phenotype of delayed puberty; and (3) although affected individuals display minimal responses to pulsatile gonadotropin-releasing hormone (<a href="/entry/152760">152760</a>), as observed in other AHC kindreds, subtle differences in gonadotropin patterns may nevertheless exist between affected individuals within a kindred. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10599709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, LEU381HIS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894899 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894899;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=rs104894899" 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=rs104894899" 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=RCV000011718" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011718" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011718</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#3" class="mim-tip-reference" title="Achermann, J. C., Silverman, B. L., Habiby, R. L., Jameson, J. L. <strong>Presymptomatic diagnosis of X-linked adrenal hypoplasia congenita by analysis of DAX1.</strong> J. Pediat. 137: 878-881, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11113848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11113848</a>] [<a href="https://doi.org/10.1067/mpd.2000.108567" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11113848">Achermann et al. (2000)</a> identified a leu381-to-his (L381H) mutation in the DAX1 gene in 2 brothers who were variably affected with AHC (<a href="/entry/300200">300200</a>). The older brother presented in the first year of life, whereas the younger brother was asymptomatic and normally pigmented at 8 months of age. Although the younger brother had normal basal adrenal steroid concentrations, dynamic testing revealed that he had impaired adrenal reserves and therefore compensated primary adrenal failure. The mutation changes an amino acid located within the putative ligand-binding domain of the nuclear receptor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11113848" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, 1-BP INS, 430G
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011719" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011719" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011719</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#8" class="mim-tip-reference" title="Domenice, S., Latronico, A. C., Brito, V. N., Arnhold, I. J. P., Kok, F., Mendonca, B. B. <strong>Adrenocorticotropin-dependent precocious puberty of testicular origin in a boy with X-linked adrenal hypoplasia congenita due to a novel mutation in the DAX1 gene.</strong> J. Clin. Endocr. Metab. 86: 4068-4071, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11549627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11549627</a>] [<a href="https://doi.org/10.1210/jcem.86.9.7816" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11549627">Domenice et al. (2001)</a> reported a 2-year-old Brazilian boy with congenital adrenal hypoplasia (AHC; <a href="/entry/300200">300200</a>) and transient precocious puberty who had a 1-bp insertion in exon 1 of the DAX1 gene (430insG), which was predicted to result in a novel frameshift mutation and a premature stop codon at position 71. Initial clinical manifestation was isosexual gonadotropin-independent precocious puberty. The authors concluded that chronic excessive ACTH levels resulting from adrenal insufficiency may stimulate Leydig cells and lead to gonadotropin-independent precocious puberty in some boys with DAX1 gene mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11549627" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, TYR380ASP
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894900 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894900;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=rs104894900" 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=rs104894900" 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=RCV000011720" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011720" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011720</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#25" class="mim-tip-reference" title="Mantovani, G., Ozisik, G., Achermann, J. C., Romoli, R., Borretta, G., Persani, L., Spada, A., Jameson, J. L., Beck-Peccoz, P. <strong>Hypogonadotropic hypogonadism as a presenting feature of late-onset X-linked adrenal hypoplasia congenital.</strong> J. Clin. Endocr. Metab. 87: 44-48, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11788621/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11788621</a>] [<a href="https://doi.org/10.1210/jcem.87.1.8163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11788621">Mantovani et al. (2002)</a> reported AHC (<a href="/entry/300200">300200</a>) in a patient who presented with hypogonadotropic hypogonadism at 28 years of age. Although the patient had no clinical evidence of adrenal dysfunction, compensated primary adrenal failure was diagnosed by biochemical testing. Semen analysis showed azoospermia, and the patient did not achieve fertility after 8 months of treatment with gonadotropins. A novel tyr380-to-asp (Y380D) missense mutation in the DAX1 gene, which caused partial loss of function in transient gene expression assays, was found. The authors concluded that partial loss-of-function mutations in DAX1 can present with HHG and covert adrenal failure in adulthood. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11788621" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, 2.2-KB DEL/27-BP INS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000011721" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011721" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011721</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#40" class="mim-tip-reference" title="Salvi, R., Gomez, F., Fiaux, M., Schorderet, D., Jameson, J. L., Achermann, J. C., Gaillard, R. C., Pralong, F. P. <strong>Progressive onset of adrenal insufficiency and hypogonadism of pituitary origin caused by a complex genetic rearrangement within DAX-1.</strong> J. Clin. Endocr. Metab. 87: 4094-4100, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12213854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12213854</a>] [<a href="https://doi.org/10.1210/jc.2001-011930" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12213854">Salvi et al. (2002)</a> reported a patient who was diagnosed with adrenal failure (AHC; <a href="/entry/300200">300200</a>) at 6 weeks of age, but who experienced transient recovery of adrenal function of several months' duration later in infancy. He subsequently failed to undergo puberty because of hypogonadotropic hypogonadism of pituitary origin, and he was also diagnosed with schizophrenia in early adulthood. Molecular genetic analyses revealed a complex rearrangement in DAX1, including a 2.2-kb deletion spanning the entire second exon and a small 27-bp insertion. The deletion extended from position 4561 through position 6801, completely eliminating exon 2 of the gene. The putative protein encoded by this mutated gene is 429 amino acids long. The initial 389 residues probably correspond to the wildtype DAX1 sequence, whereas the last 40 amino acids are presumably completely unrelated, being transcribed from the intronic sequence adjacent to exon 1. In vitro functional analyses confirmed the absence of repressor activity exerted by the mutant protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12213854" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, TYR399TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894906 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894906;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=rs104894906" 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=rs104894906" 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=RCV000011722" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011722" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011722</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the proband of a 5-generation Scottish kindred, 3 members of which had adrenal hypoplasia (<a href="/entry/300200">300200</a>), <a href="#5" class="mim-tip-reference" title="Brown, P., Scobie, G. A., Townsend, J., Bayne, R. A. L., Seckl, J. R., Saunders, P. T. K., Anderson, R. A. <strong>Identification of a novel missense mutation that is as damaging to DAX-1 repressor function as a nonsense mutation.</strong> J. Clin. Endocr. Metab. 88: 1341-1349, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12629128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12629128</a>] [<a href="https://doi.org/10.1210/jc.2002-021560" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12629128">Brown et al. (2003)</a> identified a C-to-A transversion in the second exon of the DAX1 gene that resulted in the change of tyr399 to a premature stop codon (Y399X), which truncates the DAX1 protein by 71 amino acids. Kindred analysis established that the mutation had been inherited from the proband's mother. The proband, his deceased brother, and a maternal cousin were hemizygous for the mutation. The mutation was associated with loss of Leydig cell responsiveness to human chorionic gonadotropin (see <a href="/entry/118860">118860</a>); the 35-year-old proband exhibited hypogonadotropic hypogonadism. Immunohistochemical analysis of testicular tissue obtained from the proband's affected sib, who had died from adrenal failure as a neonate, showed normal testicular morphology and expression of DAX1, steroidogenic factor-1 (<a href="/entry/184757">184757</a>), and anti-mullerian hormone (<a href="/entry/600957">600957</a>). Transient transfection assays demonstrated that the mutation resulted in a severe loss of DAX1 repressor activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12629128" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, LEU297PRO
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894907 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894907;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=rs104894907" 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=rs104894907" 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=RCV000011723 OR RCV003764556" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011723, RCV003764556" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011723...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the 34-year-old male proband of an English kindred with adrenal hypoplasia and hypogonadotropic hypogonadism (<a href="/entry/300200">300200</a>), <a href="#5" class="mim-tip-reference" title="Brown, P., Scobie, G. A., Townsend, J., Bayne, R. A. L., Seckl, J. R., Saunders, P. T. K., Anderson, R. A. <strong>Identification of a novel missense mutation that is as damaging to DAX-1 repressor function as a nonsense mutation.</strong> J. Clin. Endocr. Metab. 88: 1341-1349, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12629128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12629128</a>] [<a href="https://doi.org/10.1210/jc.2002-021560" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12629128">Brown et al. (2003)</a> identified a T-to-C transition in exon 1 of the DAX1 gene, resulting in a leu297-to-pro amino acid change (L297P). Responsiveness to human chorionic gonadotropin (see <a href="/entry/118860">118860</a>) was maintained. Kindred analysis established that the mutation had been inherited from the proband's mother. The L297P mutation occurred within a highly conserved binding motif (LLXLXL). Transient transfection assays demonstrated that the mutation resulted in a severe loss of DAX1 repressor activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12629128" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, GLN37TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894908 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894908;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=rs104894908" 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=rs104894908" 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=RCV000011724" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011724" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011724</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 20-year-old male with an unusual form of congenital adrenal hypoplasia (AHC; <a href="/entry/300200">300200</a>) manifest as late-onset adrenal insufficiency and gonadal failure, <a href="#34" class="mim-tip-reference" title="Ozisik, G., Mantovani, G., Achermann, J. C., Persani, L., Spada, A., Weiss, J., Beck-Peccoz, P., Jameson, J. L. <strong>An alternate translation initiation site circumvents an amino-terminal DAX1 nonsense mutation leading to a mild form of X-linked adrenal hypoplasia congenita.</strong> J. Clin. Endocr. Metab. 88: 417-423, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12519885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12519885</a>] [<a href="https://doi.org/10.1210/jc.2002-021034" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12519885">Ozisik et al. (2003)</a> demonstrated a C-to-T transition in the DAX1 gene that resulted in a gln37-to-ter (Q37X) substitution, predicted to cause severe truncation of the protein. Using a combination of in vitro translation assays and studies of DAX1 expression and function in transfected cells, they demonstrated that, in contrast to more distal mutations leading to a nonfunctional protein, this mutation is associated with a milder phenotype due to the expression of a partially functional, amino-truncated DAX1 protein generated from an alternate in-frame translation start site (methionine, codon 83). The production of this amino-truncated isoform appears to rescue the classical AHC phenotype, thereby delaying the onset of clinically significant adrenal dysfunction until early adulthood. <a href="#34" class="mim-tip-reference" title="Ozisik, G., Mantovani, G., Achermann, J. C., Persani, L., Spada, A., Weiss, J., Beck-Peccoz, P., Jameson, J. L. <strong>An alternate translation initiation site circumvents an amino-terminal DAX1 nonsense mutation leading to a mild form of X-linked adrenal hypoplasia congenita.</strong> J. Clin. Endocr. Metab. 88: 417-423, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12519885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12519885</a>] [<a href="https://doi.org/10.1210/jc.2002-021034" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12519885">Ozisik et al. (2003)</a> concluded that this case demonstrated a relatively rare phenomenon by which the clinical severity of an inherited human disease is reduced after alternate translation from a site downstream of a premature stop codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12519885" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, TRP105CYS
|
|
</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> rs132630327 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs132630327;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/rs132630327?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=rs132630327" 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=rs132630327" 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=RCV000011725 OR RCV002496328" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000011725, RCV002496328" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000011725...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant, formerly titled ISOLATED MINERALOCORTICOID DEFICIENCY, has been reclassified based on the findings of <a href="#49" class="mim-tip-reference" title="Verrijn Stuart, A. A., Ozisik, G., de Vroede, M. A., Giltay, J. C., Sinke, R. J., Peterson, T. J., Harris, R. M., Weiss, J., Jameson, J. L. <strong>An amino-terminal DAX1 (NR0B1) missense mutation associated with isolated mineralocorticoid deficiency.</strong> J. Clin. Endocr. Metab. 92: 755-761, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17164309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17164309</a>] [<a href="https://doi.org/10.1210/jc.2005-2429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17164309">Verrijn Stuart et al. (2007)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17164309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an 11-year-old prepubertal Dutch boy with a mild form of congenital adrenal hypoplasia (AHC; see <a href="/entry/300200">300200</a>) involving prominent hypoaldosteronism without clear evidence of glucocorticoid insufficiency, <a href="#49" class="mim-tip-reference" title="Verrijn Stuart, A. A., Ozisik, G., de Vroede, M. A., Giltay, J. C., Sinke, R. J., Peterson, T. J., Harris, R. M., Weiss, J., Jameson, J. L. <strong>An amino-terminal DAX1 (NR0B1) missense mutation associated with isolated mineralocorticoid deficiency.</strong> J. Clin. Endocr. Metab. 92: 755-761, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17164309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17164309</a>] [<a href="https://doi.org/10.1210/jc.2005-2429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17164309">Verrijn Stuart et al. (2007)</a> identified a G-to-C transversion in the NR0B1 gene, resulting in a trp105-to-cys (W105C) substitution in the N terminus of DAX1. In vitro studies of DAX1 expression and function in transfected cells demonstrated mild loss of both repression and activation functions; structure-function analysis suggested that mutations in the N terminus are compensated by the presence of repeat LXXLL motifs that mediate DAX1 interactions with other proteins. An initial ACTH stimulation test in the proband revealed subnormal cortisol results; however, a second test showed normal cortisol values, and he did not experience adrenal crisis while on mineralocorticoid treatment only. The mutation, which was not found in 100 Dutch controls, was present in the proband's mother and was also detected in 3 asymptomatic male relatives. <a href="#49" class="mim-tip-reference" title="Verrijn Stuart, A. A., Ozisik, G., de Vroede, M. A., Giltay, J. C., Sinke, R. J., Peterson, T. J., Harris, R. M., Weiss, J., Jameson, J. L. <strong>An amino-terminal DAX1 (NR0B1) missense mutation associated with isolated mineralocorticoid deficiency.</strong> J. Clin. Endocr. Metab. 92: 755-761, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17164309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17164309</a>] [<a href="https://doi.org/10.1210/jc.2005-2429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17164309">Verrijn Stuart et al. (2007)</a> suggested that phenotypic heterogeneity might result from the effects of other genes that modify or compensate for NR0B1 function, or that environmental events or exposure to medications might unmask underlying adrenal dysfunction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17164309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
NR0B1, TRP39TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1569269179 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1569269179;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=rs1569269179" 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=rs1569269179" 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=RCV000239459" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000239459" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000239459</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 32-year-old male proband with adrenal insufficiency (AHC; <a href="/entry/300200">300200</a>) who had been referred for infertility, <a href="#38" class="mim-tip-reference" title="Raffin-Sanson, M.-L., Oudet, B., Salenave, S., Brailly-Tabard, S., Pehuet, M., Christin-Maitre, S., Morel, Y., Young, J. <strong>A man with a DAX1/NR0B1 mutation, normal puberty, and an intact hypothalamic-pituitary-gonadal axis but deteriorating oligospermia during long-term follow-up.</strong> Europ. J. Endocr. 168: K45-K50, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23384712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23384712</a>] [<a href="https://doi.org/10.1530/EJE-12-1055" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23384712">Raffin-Sanson et al. (2013)</a> detected hemizygosity for an A-to-G transition in the NR0B1 gene that resulted in substitution of a termination codon for trp39 (W39X). The mutation was also found in the proband's younger brother and nephew. The proband had been diagnosed with adrenal insufficiency at age 19 years and oligospermia at age 24 years. Biologic and hormonal explorations confirmed primary adrenal insufficiency, and computed tomography showed bilateral adrenal atrophy. Puberty had been spontaneous at age 13 years, with normal virilization, growth spurt, and testicular growth. Plasma total testosterone level remained normal throughout 25 years of follow-up, whereas oligospermia worsened over time. The patient fathered 1 child at age 33 through in vitro fertilization and another 2 years later after spontaneous conception. The proband's brother was normally virilized but had azoospermia and low testosterone; he exhibited an abnormal cortisol response to the standard-dose cortrosyn test, consistent with mild adrenal insufficiency. The proband's nephew had an adrenal crisis during the second week of life. He had normal testes and genitalia, but elevated plasma ACTH and renin levels confirmed primary adrenal insufficiency. <a href="#38" class="mim-tip-reference" title="Raffin-Sanson, M.-L., Oudet, B., Salenave, S., Brailly-Tabard, S., Pehuet, M., Christin-Maitre, S., Morel, Y., Young, J. <strong>A man with a DAX1/NR0B1 mutation, normal puberty, and an intact hypothalamic-pituitary-gonadal axis but deteriorating oligospermia during long-term follow-up.</strong> Europ. J. Endocr. 168: K45-K50, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23384712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23384712</a>] [<a href="https://doi.org/10.1530/EJE-12-1055" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23384712">Raffin-Sanson et al. (2013)</a> stated that this was the first reported case of long-term preservation of gonadotrope function in a patient with markedly defective spermatogenesis due to an NR0B1 mutation, and concluded that the phenotypes of the proband, his brother, and his nephew illustrate the different possible adrenal consequences of identical NR0B1 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23384712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Achermann1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Achermann, J. C., Gu, W.-X., Kotlar, T. J., Meeks, J. J., Sabacan, L. P., Seminara, S. B., Habiby, R. L., Hindmarsh, P. C., Bick, D. P., Sherins, R. J., Crowley, W. F., Jr., Layman, L. C., Jameson, J. L.
|
|
<strong>Mutational analysis of DAX1 in patients with hypogonadotropic hypogonadism or pubertal delay.</strong>
|
|
J. Clin. Endocr. Metab. 84: 4497-4500, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10599708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10599708</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10599708" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.84.12.6269" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Achermann1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Achermann, J. C., Ito, M., Ito, M., Hindmarsh, P. C., Jameson, J. L.
|
|
<strong>A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans. (Letter)</strong>
|
|
Nature Genet. 22: 125-126, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369247</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10369247" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/9629" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Achermann2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Achermann, J. C., Silverman, B. L., Habiby, R. L., Jameson, J. L.
|
|
<strong>Presymptomatic diagnosis of X-linked adrenal hypoplasia congenita by analysis of DAX1.</strong>
|
|
J. Pediat. 137: 878-881, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11113848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11113848</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11113848" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1067/mpd.2000.108567" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Bardoni1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bardoni, B., Zanaria, E., Guioli, S., Floridia, G., Worley, K. C., Tonini, G., Ferrante, E., Chiumello, G., McCabe, E. R. B., Fraccaro, M., Zuffardi, O., Camerino, G.
|
|
<strong>A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal.</strong>
|
|
Nature Genet. 7: 497-501, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951319/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951319</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951319" 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/ng0894-497" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Brown2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brown, P., Scobie, G. A., Townsend, J., Bayne, R. A. L., Seckl, J. R., Saunders, P. T. K., Anderson, R. A.
|
|
<strong>Identification of a novel missense mutation that is as damaging to DAX-1 repressor function as a nonsense mutation.</strong>
|
|
J. Clin. Endocr. Metab. 88: 1341-1349, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12629128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12629128</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12629128" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2002-021560" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Calvo2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Calvo, R. M., Asuncion, M., Telleria, D., Sancho, J., San Millan, J. L., Escobar-Morreale, H. F.
|
|
<strong>Screening for mutations in the steroidogenic acute regulatory protein and steroidogenic factor-1 genes, and in CYP11A and dosage-sensitive sex reversal-adrenal hypoplasia gene on the X chromosome, gene-1 (DAX-1), in hyperandrogenic hirsute women.</strong>
|
|
J. Clin. Endocr. Metab. 86: 1746-1749, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11297612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11297612</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11297612" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.86.4.7424" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Caron1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Caron, P., Imbeaud, S., Bennet, A., Plantavid, M., Camerino, G., Rochiccioli, P.
|
|
<strong>Combined hypothalamic-pituitary-gonadal defect in a hypogonadic man with a novel mutation in the DAX-1 gene.</strong>
|
|
J. Clin. Endocr. Metab. 84: 3563-3569, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10522996/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10522996</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10522996" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.84.10.6030" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Domenice2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Domenice, S., Latronico, A. C., Brito, V. N., Arnhold, I. J. P., Kok, F., Mendonca, B. B.
|
|
<strong>Adrenocorticotropin-dependent precocious puberty of testicular origin in a boy with X-linked adrenal hypoplasia congenita due to a novel mutation in the DAX1 gene.</strong>
|
|
J. Clin. Endocr. Metab. 86: 4068-4071, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11549627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11549627</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11549627" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.86.9.7816" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Guo1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guo, W., Burris, T. P., McCabe, E. R. B.
|
|
<strong>Expression of DAX-1, the gene responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism, in the hypothalamic-pituitary-adrenal/gonadal axis.</strong>
|
|
Biochem. Molec. Med. 56: 8-13, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8593542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8593542</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8593542" 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/bmme.1995.1049" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Guo1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guo, W., Burris, T. P., Zhang, Y.-H., Huang, B.-L., Mason, J., Copeland, K. C., Kupfer, S. R., Pagon, R. A., McCabe, E. R. B.
|
|
<strong>Genomic sequence of the DAX1 gene: an orphan nuclear receptor responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.</strong>
|
|
J. Clin. Endocr. Metab. 81: 2481-2486, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8675564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8675564</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8675564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.81.7.8675564" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Guo1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guo, W., Lovell, R. S., Zhang, Y.-H., Huang, B.-L., Burris, T. P., Craigen, W. J., McCabe, E. R. B.
|
|
<strong>Ahch, the mouse homologue of DAX1: cloning, characterization and synteny with GyK, the glycerol kinase locus.</strong>
|
|
Gene 178: 31-34, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8921887/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8921887</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8921887" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0378-1119(96)00320-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Habiby1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Habiby, R. L., Boepple, P., Nachtigall, L., Sluss, P. M., Crowley, W. F., Jr., Jameson, J. L.
|
|
<strong>Adrenal hypoplasia congenita with hypogonadotropic hypogonadism: evidence that DAX-1 mutations lead to combined hypothalamic and pituitary defects in gonadotropin production.</strong>
|
|
J. Clin. Invest. 98: 1055-1062, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8770879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8770879</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8770879" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI118866" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Ho2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ho, J., Zhang, Y.-H., Huang, B.-L., McCabe, E. R. B.
|
|
<strong>NR0B1A: an alternatively spliced form of NR0B1.</strong>
|
|
Molec. Genet. Metab. 83: 330-336, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15589120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15589120</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15589120" 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.ymgme.2004.10.002" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Hossain2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hossain, A., Li, C., Saunders, G. F.
|
|
<strong>Generation of two distinct functional isoforms of dosage-sensitive sex reversal-adrenal hypoplasia congenita-critical region on the X chromosome gene 1 (DAX-1) by alternative splicing.</strong>
|
|
Molec. Endocr. 18: 1428-1437, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15044589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15044589</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15044589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/me.2003-0176" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Iyer2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Iyer, A. K., Zhang, Y.-H., McCabe, E. R. B.
|
|
<strong>Dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1) (NR0B1) and small heterodimer partner (SHP) (NR0B2) form homodimers individually, as well as DAX1-SHP heterodimers.</strong>
|
|
Molec. Endocr. 20: 2326-2342, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16709599/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16709599</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16709599" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/me.2005-0383" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Iyer2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Iyer, A. K., Zhang, Y.-H., McCabe, E. R. B.
|
|
<strong>LXXLL motifs and AF-2 domain mediate SHP (NR0B2) homodimerization and DAX1 (NR0B1)-DAX1A heterodimerization.</strong>
|
|
Molec. Genet. Metab. 92: 151-159, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17686645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17686645</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17686645[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=17686645" 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.ymgme.2007.06.009" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Kang2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kang, Y., Zheng, B., Shen, B., Chen, Y., Wang, L., Wang, J., Niu, Y., Cui, Y., Zhou, J., Wang, H., Guo, X., Hu, B., Zhou, Q., Sha, J., Ji, W., Huang, X.
|
|
<strong>CRISPR/Cas9-mediated Dax1 knockout in the monkey recapitulates human AHC-HH.</strong>
|
|
Hum. Molec. Genet. 24: 7255-7264, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26464492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26464492</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26464492" 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/ddv425" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Kojima2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kojima, Y., Sasaki, S., Hayashi, Y., Umemoto, Y., Morohashi, K.-I., Kohri, K.
|
|
<strong>Role of transcription factors Ad4BP/SF-1 and DAX-1 in steroidogenesis and spermatogenesis in human testicular development and idiopathic azoospermia.</strong>
|
|
Int. J. Urol. 13: 785-793, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16834661/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16834661</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16834661" 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.1442-2042.2006.01403.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Lalli1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lalli, E., Bardoni, B., Zazopoulos, E., Wurtz, J.-M., Strom, T. M., Moras, D., Sassone-Corsi, P.
|
|
<strong>A transcriptional silencing domain in DAX-1 whose mutation causes adrenal hypoplasia congenita.</strong>
|
|
Molec. Endocr. 11: 1950-1960, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9415399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9415399</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9415399" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/mend.11.13.0038" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Lalli2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lalli, E., Ohe, K., Hindelang, C., Sassone-Corsi, P.
|
|
<strong>Orphan receptor DAX-1 is a shuttling RNA binding protein associated with polyribosomes via mRNA.</strong>
|
|
Molec. Cell. Biol. 20: 4910-4921, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10848616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10848616</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10848616[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=10848616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/MCB.20.13.4910-4921.2000" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Lehmann2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lehmann, S. G., Lalli, E., Sassone-Corsi, P.
|
|
<strong>X-linked adrenal hypoplasia congenita is caused by abnormal nuclear localization of the DAX-1 protein.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 8225-8230, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12034880/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12034880</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12034880[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=12034880" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.122044099" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Lehmann2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lehmann, S. G., Wurtz, J.-M., Renaud, J.-P., Sassone-Corsi, P., Lalli, E.
|
|
<strong>Structure-function analysis reveals the molecular determinants of the impaired biological function of DAX-1 mutants in AHC patients.</strong>
|
|
Hum. Molec. Genet. 12: 1063-1072, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12700175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12700175</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12700175" 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/ddg108" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Lin2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lin, L., Gu, W.-X., Ozisik, G., To, W. S., Owen, C. J., Jameson, J. L., Achermann, J. C.
|
|
<strong>Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (NR5A1) in children and adults with primary adrenal failure: ten years' experience.</strong>
|
|
J. Clin. Endocr. Metab. 91: 3048-3054, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16684822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16684822</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16684822[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=16684822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2006-0603" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Luo1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Luo, X., Ikeda, Y., Parker, K. L.
|
|
<strong>A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation.</strong>
|
|
Cell 77: 481-490, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8187173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8187173</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8187173" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(94)90211-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Mantovani2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mantovani, G., Ozisik, G., Achermann, J. C., Romoli, R., Borretta, G., Persani, L., Spada, A., Jameson, J. L., Beck-Peccoz, P.
|
|
<strong>Hypogonadotropic hypogonadism as a presenting feature of late-onset X-linked adrenal hypoplasia congenital.</strong>
|
|
J. Clin. Endocr. Metab. 87: 44-48, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11788621/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11788621</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11788621" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.87.1.8163" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="McCabe1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McCabe, E. R. B.
|
|
<strong>Sex and the single DAX1: too little is bad, but can we have too much? (Editorial)</strong>
|
|
J. Clin. Invest. 98: 881-882, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8770856/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8770856</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8770856" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI118868" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Meeks2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meeks, J. J., Weiss, J., Jameson, J. L.
|
|
<strong>Dax1 is required for testis determination.</strong>
|
|
Nature Genet. 34: 32-33, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12679814/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12679814</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12679814" 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/ng1141" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Merke1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Merke, D. P., Tajima, T., Baron, J., Cutler, G. B., Jr.
|
|
<strong>Hypogonadotropic hypogonadism in a female caused by an X-linked recessive mutation in the DAX1 gene.</strong>
|
|
New Eng. J. Med. 340: 1248-1252, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10210708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10210708</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10210708" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM199904223401605" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Muscatelli1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Muscatelli, F., Strom, T. M., Walker, A. P., Zanaria, E., Recan, D., Meindl, A., Bardoni, B., Guioli, S., Zehetner, G., Rabl, W., Schwarz, H. P., Kaplan, J.-C., Camerino, G., Meitinger, T., Monaco, A. P.
|
|
<strong>Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.</strong>
|
|
Nature 372: 672-676, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7990958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7990958</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7990958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/372672a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Nachtigal1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nachtigal, M. W., Hirokawa, Y., Enyeart-VanHouten, D. L., Flanagan, J. N., Hammer, G. D., Ingraham, H. A.
|
|
<strong>Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression.</strong>
|
|
Cell 93: 445-454, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590178</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590178" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0092-8674(00)81172-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Nakae1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nakae, J., Abe, S., Tajima, T., Shinohara, N., Murashita, M., Igarashi, Y., Kusuda, S., Suzuki, J., Fujieda, K.
|
|
<strong>Three novel mutations and a de novo deletion mutation of the DAX-1 gene in patients with X-linked adrenal hypoplasia congenita.</strong>
|
|
J. Clin. Endocr. Metab. 82: 3835-3841, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9360549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9360549</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9360549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.82.11.4342" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Nakae1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nakae, J., Tajima, T., Kusuda, S., Kohda, N., Okabe, T., Shinohara, N., Kato, M., Murashita, M., Mukai, T., Imanaka, K., Fujieda, K.
|
|
<strong>Truncation at the C-terminus of the DAX-1 protein impairs its biological actions in patients with X-linked adrenal hypoplasia congenita.</strong>
|
|
J. Clin. Endocr. Metab. 81: 3680-3685, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8855822/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8855822</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8855822" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.81.10.8855822" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Niakan2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Niakan, K. K., McCabe, E. R. B.
|
|
<strong>DAX1 origin, function, and novel role.</strong>
|
|
Molec. Genet. Metab. 86: 70-83, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16146703/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16146703</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16146703" 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.ymgme.2005.07.019" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Ozisik2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ozisik, G., Mantovani, G., Achermann, J. C., Persani, L., Spada, A., Weiss, J., Beck-Peccoz, P., Jameson, J. L.
|
|
<strong>An alternate translation initiation site circumvents an amino-terminal DAX1 nonsense mutation leading to a mild form of X-linked adrenal hypoplasia congenita.</strong>
|
|
J. Clin. Endocr. Metab. 88: 417-423, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12519885/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12519885</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12519885" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2002-021034" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Peter1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Peter, M., Viemann, M., Partsch, C.-J., Sippell, W. G.
|
|
<strong>Congenital adrenal hypoplasia: clinical spectrum, experience with hormonal diagnosis, and report on new point mutations of the DAX-1 gene.</strong>
|
|
J. Clin. Endocr. Metab. 83: 2666-2674, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9709929/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9709929</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9709929" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.83.8.5027" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Petersen1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Petersen, K. E., Bille, T., Jacobsen, B. B., Iversen, T.
|
|
<strong>X-linked congenital adrenal hypoplasia: a study of five generations of a Greenlandic family.</strong>
|
|
Acta Paediat. Scand. 71: 947-951, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6891556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6891556</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6891556" 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.1651-2227.1982.tb09554.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Phelan2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Phelan, J. K., McCabe, E. R. B.
|
|
<strong>Mutations in NR0B1 (DAX1) and NR5A1 (SF1) responsible for adrenal hypoplasia congenita.</strong>
|
|
Hum. Mutat. 18: 472-487, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11748841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11748841</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11748841" 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.1225" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Raffin-Sanson2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Raffin-Sanson, M.-L., Oudet, B., Salenave, S., Brailly-Tabard, S., Pehuet, M., Christin-Maitre, S., Morel, Y., Young, J.
|
|
<strong>A man with a DAX1/NR0B1 mutation, normal puberty, and an intact hypothalamic-pituitary-gonadal axis but deteriorating oligospermia during long-term follow-up.</strong>
|
|
Europ. J. Endocr. 168: K45-K50, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23384712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23384712</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23384712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1530/EJE-12-1055" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Reincke1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reincke, M., Beuschlein, F., Lalli, E., Arlt, W., Vay, S., Sassone-Corsi, P., Allolio, B.
|
|
<strong>DAX-1 expression in human adrenocortical neoplasms: implications for steroidogenesis.</strong>
|
|
J. Clin. Endocr. Metab. 83: 2597-2600, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9661652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9661652</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9661652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.83.7.5095" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Salvi2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Salvi, R., Gomez, F., Fiaux, M., Schorderet, D., Jameson, J. L., Achermann, J. C., Gaillard, R. C., Pralong, F. P.
|
|
<strong>Progressive onset of adrenal insufficiency and hypogonadism of pituitary origin caused by a complex genetic rearrangement within DAX-1.</strong>
|
|
J. Clin. Endocr. Metab. 87: 4094-4100, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12213854/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12213854</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12213854" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2001-011930" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Schwartz1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schwartz, M., Blichfeldt, S., Muller, J.
|
|
<strong>X-linked adrenal hypoplasia in a large Greenlandic family. Detection of a missense mutation (N4401) in the DAX-1 gene; implication for genetic counselling and carrier diagnosis.</strong>
|
|
Hum. Genet. 99: 83-87, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9003500/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9003500</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9003500" 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/s004390050316" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Seminara1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Seminara, S. B., Achermann, J. C., Genel, M., Jameson, J. L., Crowley, W. F., Jr.
|
|
<strong>X-linked adrenal hypoplasia congenita: a mutation in DAX1 expands the phenotypic spectrum in males and females.</strong>
|
|
J. Clin. Endocr. Metab. 84: 4501-4509, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10599709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10599709</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10599709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.84.12.6172" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Swain1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Swain, A., Narvaez, V., Burgoyne, P., Camerino, G., Lovell-Badge, R.
|
|
<strong>Dax1 antagonizes Sry action in mammalian sex determination.</strong>
|
|
Nature 391: 761-767, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9486644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9486644</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9486644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/35799" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Swain1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Swain, A., Zanaria, E., Hacker, A., Lovell-Badge, R., Camerino, G.
|
|
<strong>Mouse Dax1 expression is consistent with a role in sex determination as well as in adrenal and hypothalamus function.</strong>
|
|
Nature Genet. 12: 404-409, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8630494/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8630494</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8630494" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0496-404" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Tabarin2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tabarin, A., Achermann, J. C., Recan, D., Bex, V., Bertagna, X., Christin-Maitre, S., Ito, M., Jameson, J. L., Bouchard, P.
|
|
<strong>A novel mutation in DAX1 causes delayed-onset adrenal insufficiency and incomplete hypogonadotropic hypogonadism.</strong>
|
|
J. Clin. Invest. 105: 321-328, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10675358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10675358</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10675358[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=10675358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1172/JCI7212" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Takayanagi1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Takayanagi, R., Okabe, T., Sakai, O., Nawata, H., Kato, K., Ibayashi, H.
|
|
<strong>A case of congenital adrenal hypoplasia and hypogonadism.</strong>
|
|
Horumon To Rinsho 40: 81-84, 1992.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Tamai1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tamai, K. T., Monaco, L., Alastalo, T.-P., Lalli, E., Parvinen, M., Sassone-Corsi, P.
|
|
<strong>Hormonal and developmental regulation of DAX-1 expression in Sertoli cells.</strong>
|
|
Molec. Endocr. 10: 1561-1569, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8961266/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8961266</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8961266" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/mend.10.12.8961266" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Telvi1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Telvi, L., Ion, A., Carel, J.-C., Desguerre, I., Piraud, M., Boutin, A. M., Feingold, J., Ponsot, G., Fellous, M., McElreavey, K.
|
|
<strong>A duplication of distal Xp associated with hypogonadotrophic hypogonadism, hypoplastic external genitalia, mental retardation, and multiple congenital abnormalities.</strong>
|
|
J. Med. Genet. 33: 767-771, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8880579/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8880579</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8880579" 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.33.9.767" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Verrijn Stuart2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Verrijn Stuart, A. A., Ozisik, G., de Vroede, M. A., Giltay, J. C., Sinke, R. J., Peterson, T. J., Harris, R. M., Weiss, J., Jameson, J. L.
|
|
<strong>An amino-terminal DAX1 (NR0B1) missense mutation associated with isolated mineralocorticoid deficiency.</strong>
|
|
J. Clin. Endocr. Metab. 92: 755-761, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17164309/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17164309</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17164309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2005-2429" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="50" class="mim-anchor"></a>
|
|
<a id="Wang1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, J., Killinger, D. W., Hegele, R. A.
|
|
<strong>A microdeletion within DAX-1 in X-linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism.</strong>
|
|
J. Investig. Med. 47: 232-235, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10361383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10361383</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10361383" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Yanase1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yanase, T., Takayanagi, R., Oba, K., Nishi, Y., Ohe, K., Nawata, H.
|
|
<strong>New mutations of DAX-1 genes in two Japanese patients with X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism.</strong>
|
|
J. Clin. Endocr. Metab. 81: 530-535, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8636263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8636263</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8636263" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.81.2.8636263" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Yu1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yu, R. N., Ito, M., Saunders, T. L., Camper, S. A., Jameson, J. L.
|
|
<strong>Role of Ahch in gonadal development and gametogenesis.</strong>
|
|
Nature Genet. 20: 353-357, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9843206/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9843206</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9843206" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/3822" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Zanaria1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zanaria, E., Muscatelli, F., Bardoni, B., Strom, T. M., Guioli, S., Guo, W., Lalli, E., Moser, C., Walker, A. P., McCabe, E. R. B., Meitinger, T., Monaco, A. P., Sassone-Corsi, P., Camerino, G.
|
|
<strong>An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita.</strong>
|
|
Nature 372: 635-641, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7990953/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7990953</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7990953" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/372635a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Zazopoulos1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zazopoulos, E., Lalli, E., Stocco, D. M., Sassone-Corsi, P.
|
|
<strong>DNA binding and transcriptional repression by DAX-1 blocks steroidogenesis.</strong>
|
|
Nature 390: 311-315, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9384387/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9384387</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9384387" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/36899" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Zhang1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhang, Y.-H., Guo, W., Wagner, R. L., Huang, B.-L., McCabe, L., Vilain, E., Burris, T. P., Anyane-Yeboa, K., Burghes, A. H. M., Chitayat, D., Chudley, A. E., Genel, M., and 12 others.
|
|
<strong>DAX1 mutations map to putative structural domains in a deduced three-dimensional model.</strong>
|
|
Am. J. Hum. Genet. 62: 855-864, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9529340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9529340</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9529340" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/301782" 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">
|
|
Patricia A. Hartz - updated : 09/22/2016
|
|
</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 : 08/09/2016<br>Marla J. F. O'Neill - updated : 6/29/2010<br>Patricia A. Hartz - updated : 10/29/2009<br>Marla J. F. O'Neill - updated : 9/16/2009<br>John A. Phillips, III - updated : 1/28/2008<br>Marla J. F. O'Neill - updated : 7/26/2006<br>George E. Tiller - updated : 12/20/2004<br>John A. Phillips, III - updated : 7/20/2004<br>John A. Phillips, III - updated : 3/29/2004
|
|
</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">
|
|
Cassandra L. Kniffin : 1/29/2004
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
mgross : 09/22/2016
|
|
</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">
|
|
alopez : 08/10/2016<br>alopez : 08/09/2016<br>carol : 07/28/2015<br>joanna : 9/18/2012<br>terry : 4/12/2012<br>terry : 3/15/2011<br>terry : 3/15/2011<br>alopez : 3/1/2011<br>carol : 6/29/2010<br>carol : 2/1/2010<br>carol : 1/29/2010<br>mgross : 11/4/2009<br>terry : 10/29/2009<br>carol : 10/5/2009<br>terry : 9/16/2009<br>terry : 9/16/2009<br>carol : 4/7/2009<br>terry : 3/4/2009<br>terry : 9/26/2008<br>wwang : 4/29/2008<br>wwang : 3/26/2008<br>carol : 1/28/2008<br>terry : 8/9/2007<br>carol : 7/27/2006<br>terry : 7/26/2006<br>tkritzer : 12/20/2004<br>carol : 10/12/2004<br>alopez : 7/20/2004<br>alopez : 3/29/2004<br>carol : 2/23/2004<br>ckniffin : 2/5/2004
|
|
</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> 300473
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
NUCLEAR RECEPTOR SUBFAMILY 0, GROUP B, MEMBER 1; NR0B1
|
|
|
|
</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">
|
|
DSS-AHC CRITICAL REGION ON THE X CHROMOSOME 1, GENE 1; DAX1
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: NR0B1</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 93235007;
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: Xp21.2
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : X:30,304,206-30,309,390 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
Xp21.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
46XY sex reversal 2, dosage-sensitive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
300018
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
X-linked
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Adrenal hypoplasia, congenital
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
300200
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
X-linked recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>NR0B1 (DAX1) is an orphan member of the nuclear receptor (NR) superfamily. It functions in the proper formation of the adult adrenal gland. NR0B1 has a unique role as an NR in that it acts as a coregulatory protein that inhibits the transcriptional activity of other NRs (review by Niakan and McCabe, 2005). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By identifying ESTs from the dosage-sensitive sex reversal (DSS; 300018)-congenital adrenal hypoplasia (AHC; 300200) critical region, Zanaria et al. (1994) screened human adult testis and human fetal adrenal cDNA libraries and isolated the NR0B1 gene, which they designated DAX1. The DAX1 gene encodes a deduced 470-amino acid protein that belongs to the nuclear hormone receptor superfamily and displays a novel DNA-binding domain at the N terminus. The C terminus shows characteristics of a nuclear hormone receptor ligand-binding domain. Highly significant similarity was found between the C-terminal half of DAX1 and the ligand-binding domain (domain E) of the retinoid X receptor subfamily (e.g., RXRG; 180247). Northern blot analysis detected a 1.9-kb DAX1 mRNA in adult testis and adrenal tissue. Zoo blots showed homologous fragments in all species tested, including chicken, but not in Drosophila melanogaster. Dosage analysis suggested that the cross-hybridizing fragments in mammals are X-linked. </p><p>By Northern blot analysis, Guo et al. (1995) found that DAX1 was expressed in the hypothalamus and pituitary, in addition to the gonads and adrenal cortex. </p><p>Guo et al. (1996) cloned Ahch, the mouse homolog of DAX1. They noted that the cysteine residues of the putative zinc finger DNA-binding region of DAX1 are conserved in Ahch, suggesting that this region is functional. Swain et al. (1996) isolated the mouse Dax1 gene and found that the coding sequences of human and mouse DAX1 are more similar at the DNA than at the protein levels, suggesting rapid evolution. </p><p>By 3-prime RACE of a testis cDNA library, Hossain et al. (2004) cloned a splice variant of DAX1 that they called DAX1-alpha. The deduced 401-amino acid DAX1-alpha protein is identical to DAX1 for the first 389 amino acids, including 3.5 repeats of a 65- to 67-amino acid sequence rich in alanine and glycine. However, DAX1-alpha has a unique 12-amino acid C terminus instead of the transcriptional repression domain of DAX1. RT-PCR showed highest expression of DAX1-alpha in adult testis, followed by fetal kidney and adult adrenal gland, brain, pancreas, ovary, breast, and thymus, with low expression in all other adult tissues examined. DAX1 showed highest expression in adult testis, with much lower levels in fetal kidney and adult adrenal gland, brain, ovary, and pancreas, and no expression in all other tissues examined. Real-time RT-PCR showed that DAX1-alpha predominated in all tissues tested except testis, where DAX1 predominated. Western blot analysis using an antibody directed to the common N terminus of DAX1 and DAX1-alpha detected high levels of both proteins in testis and much weaker expression of DAX1-alpha only in breast. </p><p>Ho et al. (2004) identified a DAX1 splice variant similar to DAX1-alpha that they called DAX1A. The deduced 400-amino acid DAX1A protein is identical to DAX1 over the first 389 amino acids. DAX1A differs at its C-terminal end from the DAX1-alpha protein reported by Hossain et al. (2004). RT-PCR detected highest DAX1A expression in testis, ovary, and adrenal gland, with weaker expression in pancreas. DAX1 showed highest expression in lung, pancreas, testis, ovary, and adrenal gland, with weaker expression in brain, spleen, thymus, prostate, and small intestine. Database analysis suggested the presence of DAX1A in chimpanzee, but not in rodent or chicken. </p><p>Iyer et al. (2006) stated that each of the 3 full-length N-terminal repeats in DAX1 contains LxxLL nuclear receptor boxes. The C terminus of DAX1 contains a transcriptional silencing domain and an activation factor (AF)-2 domain, and these are absent in DAX1A. </p><p>Using immunohistochemistry in rats to analyze NR0B1 expression during steroidogenesis and spermatogenesis, Kojima et al. (2006) observed strong expression in both Leydig and Sertoli cells. The intensity of expression was the same at all 14 cyclical stages of spermatogenesis in 7-day- and 21-day-old rats, but showed a stage-specific pattern in the 56-day-old sexually mature rat, with peak immunostaining during spermatogenesis stages VII to XII, coinciding with stages of major events in spermatogenesis. In humans, quantitative RT-PCR and Western blot analysis of testicular tissue obtained from males at ages ranging from 1 year to 26 years showed increased expression with increasing age during testicular development. In pubertal and adult testes, NR0B1 was abundantly expressed in the nuclei of Sertoli cells, but only a few Leydig cells were faintly NR0B1-positive. Kojima et al. (2006) concluded that expression of NR0B1 is developmentally regulated, with maximal expression during puberty and high expression after puberty. </p><p>Using Western blot analysis, Kang et al. (2015) detected Dax1 expression in testis, adrenal gland, placenta, and ovary of cynomolgus monkey. Dax1 expression was absent in heart, liver, spleen, lung, kidney, skeletal muscle, small intestine, brain, and uterus. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Zanaria et al. (1994) and Guo et al. (1996) determined that the DAX1 gene contains 2 exons. </p><p>Independently, Hossain et al. (2004) and Ho et al. (2004) identified an alternatively spliced exon, which they called exon 2-alpha or 2A, respectively, between NR0B1 exons 1 and 2. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Zanaria et al. (1994) identified the DAX1 gene within the DSS/AHC critical region on the X chromosome. Guo et al. (1996) found tight linkage between the mouse Ahch, glycerol kinase (300474), and dystrophin (300377) genes, thus showing that this region is syntenic with the homologous region of the human X chromosome. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Zanaria et al. (1994) found that the DAX1 protein is an unusual member of the nuclear hormone-receptor superfamily and acts as a dominant-negative regulator of transcription mediated by the retinoic acid receptor. The DAX1 protein is localized mainly in the nucleus and can bind to an RA responsive element (RARE). </p><p>Swain et al. (1996) found that the mouse Dax1 gene is expressed in the first stages of gonadal and adrenal differentiation and in the developing hypothalamus. Moreover, Dax1 expression is downregulated coincident with overt differentiation in the testis, but persists in the developing ovary. They suggested that these results provided a basis for adrenal insufficiency and hypogonadotropic hypogonadism in males affected by congenital adrenal hypoplasia and were consistent with a role for DAX1 in gonadal sex determination. </p><p>Tamai et al. (1996) demonstrated that DAX1 is expressed in the Sertoli cells of rat testis. This expression is regulated during spermatogenesis and peaks during the androgen-sensitive phase of the spermatogenic cycle. They also found that DAX1 expression in Sertoli cells is regulated developmentally. Maximum levels are present in the rat between postnatal days 20 and 30, during the first spermatogenic wave. Furthermore, activation of the cAMP-signaling pathway by follicle-stimulating hormone (FSH; see 136530) causes downregulation of DAX1 expression in cultured Sertoli cells. These data indicated that DAX1 expression in Sertoli cells may influence the development of spermatogenic cells in response to steroid and pituitary hormones. </p><p>Binding sites for the DAX1 protein are found in the promoters of the DAX1 and steroidogenic acute regulatory protein (STAR; 600617) genes. Zazopoulos et al. (1997) showed that DAX1 binds DNA and acts as a powerful transcriptional repressor of STAR gene expression, leading to a drastic decrease in steroid production. They provided in vitro and in vivo evidence that DAX1 binds to DNA hairpin structures. The results established that DAX1 is the first member of the nuclear receptor superfamily with novel DNA-binding features. They showed that it has regulatory properties critical to the understanding of its physiologic functions. </p><p>The finding of Muscatelli et al. (1994) that point mutations in the DAX1 gene cause AHC and HHG (see MOLECULAR GENETICS) strongly suggested that DAX1 is essential for the development of a functioning hypothalamus-pituitary-gonadal axis. The authors noted that, in mice, disruption of the Ftz-F1 autosomal gene, which encodes the nuclear hormone receptor SF1 (NR5A1; 184757), prevents the development of adrenal glands and gonads (Luo et al., 1994). In the human male, disruption of DAX1 does not prevent the initial stages of gonadal development, but the adrenal does not differentiate beyond the fetal stage. Achermann et al. (1999) found that mutation in the human NR5A1 gene results in XY sex reversal with adrenal failure. </p><p>DAX1 binds to hairpin secondary structures and blocks steroidogenesis in adrenal cells by transcriptional repression of the STAR promoter. Lalli et al. (1997) investigated the molecular mechanism of this repression. They found that the DAX1 C terminus contains transcriptional silencing activity, which can be transferred to a heterologous DNA-binding domain. Two cooperating domains are required for the silencing function, one located within helix H3 and the other within H12. The silencing function is cell- and promoter-specific. By confocal and immunogold electron microscopy, Lalli et al. (2000) showed that DAX1 is localized in both the cytoplasm and nucleus of human adrenal cortex and mouse Leydig tumor cells. Much of the DAX1 is associated with polyribosomes in complexes with polyadenylated RNA. The 3 N-terminal repeats act cooperatively to direct DAX1 binding to RNA, and the C-terminal ligand-binding domain (LBD) also functions as an autonomous RNA-binding domain. </p><p>Reincke et al. (1998) investigated the expression of DAX1 in a variety of adrenocortical tumors and compared the results with STAR mRNA expression. They found low or absent DAX1 expression in aldosterone-producing adenomas and in aldosterone-producing adrenocortical carcinomas. Cortisol-producing adenomas showed intermediate DAX1 expression (n = 8; 92 +/- 16%), as did 3 non-aldosterone-producing carcinomas (72%, 132%, and 132%). High DAX1 expression was present in nonfunctional adenomas (n = 3; 160 +/- 17%). In contrast to DAX1, STAR mRNA expression did not show significant variations between groups. Reincke et al. (1998) concluded that high DAX1 expression in adrenocortical tumors is associated with a nonfunctional phenotype, whereas low DAX1 expression favors mineralocorticoid secretion, and that these effects on steroidogenesis are mediated by mechanisms other than repression of STAR gene expression. They suggested that DAX1 may be one of the factors influencing the steroid biosynthesis of adrenocortical neoplasms. </p><p>XY individuals carrying duplications of Xp21 undergo sex reversal and develop as females. Swain et al. (1998) noted that XY mice carrying extra copies of Dax1 as a transgene show delayed testis development when the gene is expressed at high levels, but do not normally show sex reversal. Swain et al. (1998) found that complete sex reversal occurred, however, when the transgene was tested against weak alleles of the sex-determining Y-chromosome gene Sry (480000). These results showed that Dax1 is largely, if not solely, responsible for dosage-sensitive sex reversal and provided a model for early events in mammalian sex determination, when precise levels and timing of gene expression are critical. The results of Swain et al. (1998) indicated that Dax1 functions as an anti-testis gene by acting antagonistically to Sry. The orphan nuclear receptor Dax1 was originally proposed to act as an 'anti-testis' factor. In studies in the mouse, however, Meeks et al. (2003) found that Nr0b1 is in fact required for testis differentiation. Sex reversal in the absence of Dax1 occurred after normal expression of Sry, suggesting that Sry and Dax1 are both required for normal testis determination. </p><p>Nachtigal et al. (1998) showed that WT1(-KTS) (607102) isoforms associated and synergized with SF1 (184757) to promote mullerian inhibiting substance (MIS, or AMH; 600957) expression. In contrast, WT1 missense mutations, associated with male pseudohermaphroditism in Denys-Drash syndrome (194080), failed to synergize with SF1. DAX1 antagonized synergy between SF1 and WT1, most likely through a direct interaction with SF1. Nachtigal et al. (1998) proposed that WT1 and DAX1 functionally oppose each other in testis development by modulating SF1-mediated transactivation. </p><p>By coexpression in HeLa cells, Hossain et al. (2004) confirmed that DAX1 repressed SF1-mediated expression of reporter gene driven by the STAR promoter. DAX1-alpha relieved this repression in a dose-dependent manner. Similar results were obtained with a reporter construct containing the CYP17 (CYP17A1; 609300) promoter. Like DAX1, in vitro-translated DAX1-alpha bound a hairpin DNA structure in the STAR promoter. SF1 coprecipitated with both DAX1 and DAX1-alpha, but only DAX1 bound the promoter region of Alien (COPS2; 604508). Hossain et al. (2004) concluded that DAX1-alpha antagonizes the transcriptional repression activity of DAX1. </p><p>Using a yeast 2-hybrid system and transfected HEK293 cells, Iyer et al. (2006) showed that DAX1 homodimerized. In HEK293 cells, homodimers were detected in both the nucleus and cytoplasm, and the homodimers dissociated upon heterodimerization with SF1 or ligand-activated ER-alpha (ESR1; 133430). Homodimerization of DAX1 appeared to be mediated by antiparallel interaction between its N-terminal LxxLL motifs and C-terminal AF2 domain. SHP (NR0B2; 604630) formed a similar antiparallel homodimer via its N-terminal LxxLL motifs and C-terminal AF2 domain, and DAX1 could form a heterodimer with SHP and also with DAX1A. </p><p>Iyer et al. (2007) showed that the DAX1-DAX1A interaction was mediated by the LxxLL domain of DAX1A and the AF2 domain of DAX1. DAX1A localized predominantly to the cytoplasm, whereas DAX1-DAX1A heterodimers localized to the nucleus, suggesting different functions for DAX1A in each compartment. </p><p>Kojima et al. (2006) analyzed expression levels of NR0B1 mRNA in testicular tissue from 22 patients with nonobstructive azoospermia and detected NR0B1 in all specimens. Quantitative RT-PCR showed no significant relationship between the expression level of NR0B1 and serum testosterone concentration. However, the average expression levels of NR0B1 mRNA were significantly lower in patients with maturation arrest and Sertoli cell-only syndrome compared to patients with hypospermatogenesis or men with normal spermatogenesis and obstructive azoospermia, suggesting that the function of NR0B1 in Sertoli cells is required for normal spermatogenesis and fertility. </p><p><strong><em>Reviews</em></strong></p><p>
|
|
Niakan and McCabe (2005) reviewed the origin and function of DAX1 in human and mouse. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Congenital Adrenal Hypoplasia</em></strong></p><p>
|
|
Muscatelli et al. (1994) demonstrated that mutations in the DAX1 gene give rise to X-linked congenital adrenal hypoplasia with hypogonadotropic hypogonadism (AHC; 300200). In 6 patients with AHC and 12 patients who had AHC with glycerol kinase deficiency (GKD; 307030) or AHC-GKD with Duchenne muscular dystrophy (DMD) (see chromosome Xp21 deletion syndrome, 300679), DAX1 was deleted. In 11 AHC families, and 1 sporadic case, point mutations were found in the coding region of the DAX1 gene (see, e.g., 300473.0001-300473.0005). All AHC patients over 14 years of age and with only point mutations in DAX1 were also found to have hypogonadotropic hypogonadism, confirming that the DAX1 gene is responsible for both findings. However, in 4 sporadic cases and a single familial case of AHC, no point mutations were found, suggesting genetic heterogeneity. </p><p>Guo et al. (1996) used SSCP analysis to identify 3 new DAX1 gene mutations as well as polymorphisms that may permit linkage analysis in families without identified mutations. </p><p>Adrenal hypoplasia typically presents as adrenal insufficiency during infancy, whereas hypogonadotropic hypogonadism becomes evident in affected males who survive into childhood and approach puberty. Habiby et al. (1996) identified mutations in the DAX1 gene in 2 affected members of 2 kindreds. Studies of baseline levels of luteinizing hormone (152780), FSHB (136530), and chorionic gonadotropin alpha (CGA; 118850) demonstrated differences between the 2 families and suggested to Habiby et al. (1996) that DAX1 mutations impair gonadotropin production by acting at both the hypothalamic and pituitary levels. McCabe (1996) agreed with these conclusions, noting that loss of DAX1 results in adrenal hypoplasia and hypogonadotropic hypogonadism, and increased DAX1 leads to dosage-sensitive sex reversal and a female phenotype or ambiguous genitalia in XY-genotypic males. </p><p>Zhang et al. (1998) identified 14 new mutations in 17 families with AHC, bringing the total number of families with AHC studied to 48 and the number of reported mutations to 42; 1 family showed gonadal mosaicism. These mutations included 23 frameshift, 12 nonsense, and 6 missense mutations, and 1 single-codon deletion. They mapped 7 single amino acid changes to a homology model constructed by use of the 3-dimensional crystal structure of the thyroid hormone receptor (190160) and retinoid X receptor-alpha (180245). All single amino acid changes mapped to the C-terminal half of the DAX1 protein in the conserved hydrophobic core of the putative ligand-binding domain, and no affected residue was expected to interact directly with a ligand. Zhang et al. (1998) concluded that most genetic alterations in DAX1 are frameshift or nonsense mutations and speculated that the codon deletion and missense mutations give insight into the structure and function of DAX1. </p><p>Peter et al. (1998) studied 18 AHC boys from 16 families: 4 with AHC, GKD, and DMD; 2 with AHC and GKD; and 12 with AHC (5 young adults with hypogonadotropic hypogonadism). Most presented as neonates with salt wasting and hyperpigmentation. Aldosterone deficiency usually preceded cortisol deficiency, which explained why the patients more often presented with salt-wasting rather than with hypoglycemic symptoms. In samples from the 15 patients studied by molecular analysis of the DAX1 gene, large deletions were found in 6 patients, and point mutations in another 7. All of the point mutations identified encoded a nonfunctional, truncated DAX1 protein. Two brothers with primary adrenal insufficiency and histories strongly suggesting AHC had no mutation in the DAX1 gene, suggesting genetic heterogeneity for the disorder. </p><p>Merke et al. (1999) studied a family in which 2 males had a nonsense mutation in the DAX1 gene as the cause of congenital adrenal hypoplasia with gonadotropic hypogonadism. Their unaffected mother was heterozygous and their unaffected maternal grandfather was hemizygous for the nonsense mutation; the authors stated that the latter findings indicated a lack of penetrance of the mutation. The results of mutation analysis of DNA from urinary sediment were similar to those in leukocyte DNA. A maternal aunt, who had isolated hypogonadotropic hypogonadism, was homozygous for the mutation. This homozygosity was thought to have resulted from gene conversion, the nonreciprocal transfer of DNA from one parental allele to the other. This is a novel suggestion for manifestations in heterozygous females. </p><p>Phelan and McCabe (2001) presented a compendium of published NR0B1 mutations and polymorphisms, and discussed them in the context of known biology and clinical applicability. </p><p>Lehmann et al. (2002) noted that all known DAX1 mutations found in AHC patients alter the C terminus of the protein, which shares similarity to the ligand-binding domain of nuclear hormone receptors and bears transcriptional repressor activity. This property is invariably impaired in DAX1 AHC mutants. Lehmann et al. (2002) showed that the localization of DAX1 AHC mutant proteins is drastically shifted toward the cytoplasm, even if their nuclear localization signal, which resides in the N-terminal region of the protein, is intact. Cytoplasmic localization of DAX1 AHC mutants correlates with an impairment in their transcriptional repression activity. These results revealed a critical role of an intact C terminus in determining DAX1 subcellular localization and constituted an important example of a defect in human organogenesis caused by impaired nuclear localization of a transcription factor. </p><p>Lehmann et al. (2003) showed that several DAX1 AHC mutants had a misfolded conformation, which correlated with their cytoplasmic retention. Extensive structure-function analysis revealed that the chemical nature of amino acid residues at positions interrupted by AHC mutations and critical determinants in helix 12 affected DAX1 nuclear localization and transcriptional silencing. Mutations in a conserved putative corepressor binding surface had a negative effect upon DAX1 transcriptional repression only when they also affected protein expression levels. Lehmann et al. (2003) suggested that a folding defect underlies the impaired function of DAX1 missense mutants found in AHC/HHG patients, and that interactions with transcriptional cofactors different from known corepressors mediate DAX1 silencing properties. </p><p>In 3 male relatives with adrenal phenotypes ranging from adrenal crisis in infancy to asymptomatic adrenal insufficiency, Raffin-Sanson et al. (2013) identified a trp39-to-ter mutation in NR0B1 (W39X; 300473.0031). </p><p><strong><em>46,XY Sex Reversal</em></strong></p><p>
|
|
Bardoni et al. (1994) studied 8 patients with duplications at chromosome Xp21, including 4 who had 46,XY sex reversal (SRXY2; 300018) and 4 who were 46,XY phenotypic males. Breakpoint analysis identified an approximately 20-Mb region on Xp21.2-p22.1 that was duplicated only in the 46,XY females. Further analysis involving 1 additional 46,XY sex-reversed patient with a submicroscopic duplication on Xp defined a 160-kb critical region adjacent to the congenital adrenal hypoplasia locus (AHC; 300200) that was exclusively duplicated in the patients with male-to-female sex reversal; the authors designated the locus DSS for 'dosage-sensitive sex reversal' (see 300473.0014). </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
For discussion of a possible association between mutation in the NR0B1 gene and a form of AHC involving isolated mineralocorticoid deficiency, see 300473.0030.</p><p><strong><em>Exclusion of DAX1 Mutations</em></strong></p><p>
|
|
Telvi et al. (1996) reported GTD associated with mental retardation, facial dysmorphism, and hypoplastic external genitalia in an 18-year-old male with familial duplication of the segment Xp22.32-p22.11. Molecular analysis showed that the DAX1 gene was not involved in this duplication. Two sisters with the same inv dup(Xp) chromosome had short stature but were otherwise phenotypically normal. The abnormal X chromosome was late replicating in 96 to 98% of cells from the sisters. The authors discussed several possible explanations for the proband's phenotype. </p><p>Achermann et al. (1999) hypothesized that DAX1 might be a candidate gene in patients with idiopathic sporadic or familial HHG or constitutional delay of puberty. They performed direct sequencing of the DAX1 gene in 106 patients, including 85 (80 men and 5 women) with sporadic HHG or constitutional delay of puberty and patients from 21 kindreds with familial forms of these disorders. No DAX1 mutations were found in these groups of patients, although silent single nucleotide polymorphisms were identified. The authors concluded that mutations in DAX1 are unlikely to be a common cause of HHG or pubertal delay in the absence of a concomitant history of adrenal insufficiency. </p><p>Calvo et al. (2001) used heteroduplex analysis to screen the genes encoding STAR, SF1, DAX1, and CYP11A (118485) for mutations in genomic DNA from 19 women presenting with hirsutism and increased serum androgen levels. Analysis of DAX1 showed no variant in any of the women studied. The authors concluded that mutations in STAR, SF1, CYP11A, and DAX1 are seldom found in hirsute patients and do not explain the steroidogenic abnormalities found in these women. </p><p>Lin et al. (2006) studied the prevalence of DAX1 and SF1 mutations in 117 children and adults with primary adrenal failure of unknown etiology (i.e., not caused by congenital adrenal hyperplasia, adrenoleukodystrophy, or autoimmune disease). DAX1 mutations were found in 58% (37 of 64) of 46,XY phenotypic boys referred with adrenal hypoplasia and in all boys (8 of 8) with hypogonadotropic hypogonadism and a family history suggestive of adrenal failure in males. SF1 mutations causing adrenal failure were found in only 2 patients with 46,XY gonadal dysgenesis. No DAX1 or SF1 mutations were identified in the adult-onset group. Lin et al. (2006) concluded that DAX1 mutations are a relatively frequent cause of adrenal failure in this group of boys, whereas SF1 mutations causing adrenal failure in humans are rare and are more likely to be associated with significant underandrogenization and gonadal dysfunction in 46,XY individuals. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In the mouse, Yu et al. (1998) disrupted the Ahch gene to generate a mouse model of congenital adrenal hypoplasia with hypogonadotropic hypogonadism that allowed the function of Ahch to be examined in both males and females. Though Ahch had been postulated to function as an ovarian determination gene, the loss of Ahch function in females did not affect ovarian development or fertility. Instead, Ahch was essential for the maintenance of spermatogenesis. Lack of Ahch caused progressive degeneration of the testicular germinal epithelium independent of abnormalities in gonadotropin and testosterone production and resulted in male sterility. </p><p>Kang et al. (2015) used CRISPR/Cas9 genome engineering to mutate Dax1 in cynomolgus monkey. They obtained no live offspring with Dax1 mutations following embryo transfer, but several fetuses showed extensive Dax1 modifications, including a male fetus with targeted mutations in Dax1 in most somatic tissues and gonad. Testis of the Dax1-deficient fetus was grossly normal, but it had altered ultrastructural morphology and expansion of blood vessels. Absence of Dax1 did not alter Sertoli cell fate, testis cords were well organized, and tubular structure remained intact, but with reduced number of germ cells. Dax1-deficient testis showed normal expression of Amh, Sox9 (608160), and Wt1, but expression of the Wnt signaling protein beta-catenin (CTNNB1; 116806) was upregulated in interstitial cells, as was Vegf (VEGFA; 192240) content. Adrenal gland of the Dax1-deficient fetus showed substantial enlargement of the fetal zone. Dax1 deficiency did not cause any apparent defects in other tissues or organs. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>31 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, GLN283TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894890,
|
|
|
|
|
|
|
|
ClinVar: RCV000011696
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 44-year-old man who had AHC with hypogonadotropic hypogonadism (300200), Muscatelli et al. (1994) identified a nonsense mutation in the NR0B1 gene involving gln283 (Q283X) and leading to suppression of a PvuII site. Age at onset of the disorder was 10 days of life. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, TRP369TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894886,
|
|
|
|
|
|
|
|
ClinVar: RCV000011697
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with AHC (300200) and bilateral cryptorchidism, Muscatelli et al. (1994) identified a W369X nonsense mutation in the NR0B1 gene. Age at onset of the disorder was 17 days of life. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, LEU263TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894887,
|
|
|
|
|
|
|
|
ClinVar: RCV000011698
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient who had AHC with hypogonadotropic hypogonadism (300200), Muscatelli et al. (1994) identified a L263X nonsense mutation in the NR0B1 gene, which created a BstUI site. Age of AHC onset was 8 days of life, and age of HHG onset was before 14 years. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, ARG267PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894888,
|
|
|
|
|
|
gnomAD: rs104894888,
|
|
|
|
|
|
ClinVar: RCV000011699, RCV001851797
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 brothers with AHC with hypogonadotropic hypogonadism (300200), Muscatelli et al. (1994) identified a 1034G-A transition in the NR0B1 gene, which was predicted to generate an arg267-to-pro (R267P) substitution, and resulted in suppression of a CfoI site. </p><p>Lalli et al. (1997) found that 2 mutations in the DAX1 gene, R267P and deletion of V269, impair transcriptional silencing of the STAR promoter, suggesting that loss of the functional repression plays a role in the pathogenesis of AHC. (See also Lalli et al. (2000) and 300473.0008). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, TRP235TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894889,
|
|
|
|
|
|
|
|
ClinVar: RCV000011700
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male patient who had AHC with hypogonadotropic hypogonadism (300200), Muscatelli et al. (1994) observed a G-to-A transition in the NR0B1 gene, resulting in a nonsense mutation at codon 235 (trp235-to-ter; W235X), creating a MaeI restriction site. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, TRP171TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894891, rs104894893,
|
|
|
|
|
|
gnomAD: rs104894891,
|
|
|
|
|
|
ClinVar: RCV000011701
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese male patient, originally reported at 17 years of age by Takayanagi et al. (1992), who had AHC with hypogonadotropic hypogonadism (300200) and whose brother and 2 maternal uncles had died in infancy or early childhood of hypovolemic shock, Yanase et al. (1996) found a G-to-A transition in the NR0B1 gene, resulting in a nonsense mutation at codon 171 (trp171-to-ter; W171X). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, 1-BP DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011702
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 20-year-old Japanese man who had an apparently sporadic case of AHC with hypogonadotropic hypogonadism (300200), Yanase et al. (1996) identified a 1-bp deletion (delT) in codon 280, leading to a frameshift and a premature stop at codon 371. The mutation created a new MspI restriction site which was absent in the PCR products of both parents. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, ASN440ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28935481,
|
|
|
|
|
|
gnomAD: rs28935481,
|
|
|
|
|
|
ClinVar: RCV000011704
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 male patients with AHC (300200) from the Greenlandic family originally reported by Petersen et al. (1982), Schwartz et al. (1997) identified a 1553A-T transversion in the NR0B1 gene, resulting in an asn440-to-ile (N440I) substitution. The substitution represented change from a polar amino acid to a nonpolar amino acid. Both patients who had reached the age of puberty exhibited hypogonadotropic hypogonadism. The authors noted that among 33 female relatives at risk for the mutation, they identified 10 as carriers and excluded 23 from being carriers, information important for genetic counseling. </p><p>Lalli et al. (2000) determined that the N440I mutation results in impaired RNA-binding activity of the DAX1 protein (see also Lalli et al., 1997 and 300473.0004). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, GLN395TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894894,
|
|
|
|
|
|
|
|
ClinVar: RCV000011705, RCV000481802
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Nakae et al. (1996) characterized the DAX1 gene from 6 patients, including 2 sibs, with AHC (300200), and found 5 novel mutations including 3 nonsense and 2 frameshift mutations. The nonsense mutations were a C-to-T transition (gln395-to-ter; Q395X), a C-to-G transversion (tyr271-to-ter; Y271X; 300473.0010), and a C-to-A transversion (tyr91-to-ter; Y91X; 300473.0011). The Y91X mutation was found in 2 sibs. The frameshift mutations were a 2-bp deletion (1610delAT) and a 1-bp (G) insertion resulting in a premature stop at codon 462 (300473.0012), and a 1-bp deletion (1169delC), resulting in a frameshift which caused a premature stop codon at position 371 (300473.0013). A 21-year-old male patient in whom the Q395X mutation was identified had hypogonadotropic hypogonadism; the other 5 patients were prepubertal. All mutated NR0B1 proteins had truncated C-terminal domains, suggesting that these 5 mutations cause AHC and that the C terminus of the DAX1 protein, especially the terminal 11 amino acids, is necessary for normal adrenal cortical embryogenesis. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, TYR271TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894895,
|
|
|
|
|
|
|
|
ClinVar: RCV000011706
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 300473.0009 and Nakae et al. (1996). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, TYR91TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894892,
|
|
|
|
|
|
|
|
ClinVar: RCV000011703, RCV000413730
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 300473.0009 and Nakae et al. (1996). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, 2-BP DEL, 1610AG, AND 1-BP INS
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011707
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 300473.0009 and Nakae et al. (1996). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, 1-BP DEL, 1169C
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011708
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>See 300473.0009 and Nakae et al. (1996). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 46,XY SEX REVERSAL 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, DUP
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011709
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>XY individuals with a duplication of part of the short arm of the X chromosome and an intact SRY gene show male-to-female sex reversal (SRXY2; 300018). The single X chromosome in these individuals does not undergo X-chromosome inactivation; therefore, these individuals presumably carry 2 active copies of genes, including the NR0B1 gene, in the duplicated region. Individuals with deletion of this region develop as males. Genes within the DSS region are, therefore, not essential for testis development, but, when present in a double dose, interfere with testis formation (Swain et al., 1998). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, 2-BP DEL, 388AG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2147007424,
|
|
|
|
|
|
|
|
ClinVar: RCV001837630, RCV002280832
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Nakae et al. (1997) characterized the NR0B1 gene from 7 patients in 6 kindreds with AHC (300200) and identified 1 frameshift mutation, 2 missense mutations (see 300473.0016 and 300473.0017), and 3 deletion mutations (see 300473.0018) in the NR0B1 gene. The frameshift mutation, found in a 26-year-old male patient who had AHC with hypogonadotropic hypogonadism, was a 2-bp deletion (388delAG) resulting in a premature stop codon at position 70. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, LYS382ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894896,
|
|
|
|
|
|
|
|
ClinVar: RCV000011711
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 15-year-old male patient who had AHC with hypogonadotropic hypogonadism (300200), Nakae et al. (1997) identified a 1380G-T transversion in the NR0B1 gene, resulting in a lys382-to-asn (L382N) substitution. Lys382 is highly conserved among other related orphan nuclear receptor superfamily members. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, TRP291CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs28935482,
|
|
|
|
|
|
|
|
ClinVar: RCV000011712
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a pair of prepubertal sibs with AHC (300200), Nakae et al. (1997) identified a 1107G-C transversion in the NR0B1 gene, resulting in a trp291-to-cys (W291C) substitution. Trp291 is highly conserved among other related orphan nuclear receptor superfamily members. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011713
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>By Southern blotting and PCR of a GGAA tetranucleotide tandem repeat, Nakae et al. (1997) detected deletions in the NR0B1 gene of 3 unrelated prepubertal patients with AHC (300200). The extents of the deletions were not determined. In 2 of the patients, the deletion was familial; in the third, it was de novo. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, 4-BP DEL, NT1464
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1569268070,
|
|
|
|
|
|
|
|
ClinVar: RCV000011714, RCV002512973
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 42-year-old patient who had congenital adrenal hypoplasia with hypogonadotropic hypogonadism (300200), Wang et al. (1999) identified a 4-bp deletion (1464delACTC) in the second exon of the NR0B1 sequence, which caused a frameshift and predicted a premature stop codon at amino acid 416. The diagnosis of AHC and HHG had been made at 2 weeks of age when he presented to the Hospital for Sick Children in Toronto with vomiting, loose stools, and failure to thrive. He was treated with intramuscular deoxycortisone acetate (DOCA) and discharged with 2 subcutaneous DOCA pellets. Prednisone was started with added salt at the age of 23 months. He had been maintained on glucocorticoids since that time. At age 15 he developed a slipped left femoral epiphysis, which was treated surgically. His bone age at that time was 11 years. He had no secondary sexual development when studied at the age of 17 years and was started on testosterone. No other family members were affected. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, ILE439SER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894897,
|
|
|
|
|
|
|
|
ClinVar: RCV000011716
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a man who presented with apparently isolated adrenal insufficiency at 28 years of age, later confirmed as AHC (300200), Tabarin et al. (2000) found a missense mutation, ile439-to-ser (I439S), in the DAX1 gene. Physical examination revealed partial pubertal development and undiagnosed incomplete hypogonadotropic hypogonadism. Gonadotropin therapy did not improve his marked oligospermia, suggesting a concomitant primary testicular abnormality. The patient's complaint was fatigue for 5 years. During the year before study, the patient noted additional symptoms, such as episodes of nausea, abdominal pain, orthostatic dizziness, and loss of 4.5 kg of body weight. His height and weight were 171 cm and 58 kg, respectively, and his blood pressure was 100/60 mm Hg while supine. On physical examination, moderate and diffuse increased skin pigmentation was noted, with a few hyperpigmented macules on the lips. Facial, thoracic, and pubic hair (Tanner stage 3) were sparse, with a gynecoid distribution of subcutaneous fat. There was no gynecomastia. Penile length was normal, but testicular volume was low (6 ml bilaterally). The patient stated that puberty had occurred at the age of approximately 16. He described impaired libido and infrequent erections. </p><p>Tabarin et al. (2000) studied the mutant I439S protein for its ability to function as a transcriptional repressor of target genes. Consistent with the patient's mild clinical phenotype, the I439S mutation conferred intermediate levels of repressor activity of DAX1 when compared with mutations associated with classic AHC. This unique case extended the clinical spectrum of AHC to include delayed-onset primary adrenal insufficiency in adulthood and milder forms of HHG. In accordance with findings in Ahch(Dax1) knockout mice, the clinical features in this patient suggested that DAX1 function is required for spermatogenesis in humans, independent of its known effects on gonadotropin production. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, TYR197TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894898,
|
|
|
|
|
|
|
|
ClinVar: RCV000011715
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Caron et al. (1999) studied a 20-year-old male patient who had congenital adrenal hypoplasia with hypogonadotropic hypogonadism (300200) due to an 825C-A transversion in the NR0B1 gene, resulting in a tyr197-to-ter (Y197X) substitution. The same mutation was detected in the patient's affected first cousin and in heterozygous state in their carrier mothers. The patient had had acute adrenal insufficiency at the age of 2.5 years, bilateral cryptorchidism corrected surgically at the age of 12 years, and failure of spontaneous puberty. Plasma testosterone was undetectable and gonadotropin levels were low and not stimulated after intravenous injection of 100 microg gonadotropin-releasing hormone (GNRH; see 152760). The endogenous LH secretory pattern was apulsatile, whereas free alpha-subunit levels depicted erratic pulses, suggesting an incomplete deficiency of hypothalamic GnRH secretion. The authors concluded that the hypogonadism was due to a combined hypothalamic-pituitary-gonadal defect and implied that the NR0B1 gene may play a critical role in human testicular function. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, 1-BP DEL, 501A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1569268976,
|
|
|
|
|
|
|
|
ClinVar: RCV000011717, RCV002280091, RCV003764555
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Seminara et al. (1999) studied an extended kindred with adrenal hypoplasia congenita with hypogonadotropic hypogonadism (300200) in which 2 males (the proband and his nephew) were affected with a nucleotide deletion (501delA) in the DAX1 gene. The proband's mother, sister, and niece were heterozygous for this frameshift mutation. At age 27 years, after 7 years of low dose hCG therapy, the proband underwent a testicular biopsy revealing rare spermatogonia and Leydig cell hyperplasia. Despite steadily progressive doses of hCG and Pergonal administered over a 3-year period, the proband remained azoospermic. The proband's mother, sister (obligate carrier), and niece all had a history of delayed puberty, with menarche occurring at ages 17-18 years. The authors concluded that (1) affected males with AHC/HHG may have an intrinsic defect in spermatogenesis that is not responsive to gonadotropin therapy; (2) female carriers of DAX1 mutations may express the phenotype of delayed puberty; and (3) although affected individuals display minimal responses to pulsatile gonadotropin-releasing hormone (152760), as observed in other AHC kindreds, subtle differences in gonadotropin patterns may nevertheless exist between affected individuals within a kindred. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0023 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, LEU381HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894899,
|
|
|
|
|
|
|
|
ClinVar: RCV000011718
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Achermann et al. (2000) identified a leu381-to-his (L381H) mutation in the DAX1 gene in 2 brothers who were variably affected with AHC (300200). The older brother presented in the first year of life, whereas the younger brother was asymptomatic and normally pigmented at 8 months of age. Although the younger brother had normal basal adrenal steroid concentrations, dynamic testing revealed that he had impaired adrenal reserves and therefore compensated primary adrenal failure. The mutation changes an amino acid located within the putative ligand-binding domain of the nuclear receptor. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0024 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, 1-BP INS, 430G
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011719
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Domenice et al. (2001) reported a 2-year-old Brazilian boy with congenital adrenal hypoplasia (AHC; 300200) and transient precocious puberty who had a 1-bp insertion in exon 1 of the DAX1 gene (430insG), which was predicted to result in a novel frameshift mutation and a premature stop codon at position 71. Initial clinical manifestation was isosexual gonadotropin-independent precocious puberty. The authors concluded that chronic excessive ACTH levels resulting from adrenal insufficiency may stimulate Leydig cells and lead to gonadotropin-independent precocious puberty in some boys with DAX1 gene mutations. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0025 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, TYR380ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894900,
|
|
|
|
|
|
|
|
ClinVar: RCV000011720
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Mantovani et al. (2002) reported AHC (300200) in a patient who presented with hypogonadotropic hypogonadism at 28 years of age. Although the patient had no clinical evidence of adrenal dysfunction, compensated primary adrenal failure was diagnosed by biochemical testing. Semen analysis showed azoospermia, and the patient did not achieve fertility after 8 months of treatment with gonadotropins. A novel tyr380-to-asp (Y380D) missense mutation in the DAX1 gene, which caused partial loss of function in transient gene expression assays, was found. The authors concluded that partial loss-of-function mutations in DAX1 can present with HHG and covert adrenal failure in adulthood. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0026 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, 2.2-KB DEL/27-BP INS
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000011721
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Salvi et al. (2002) reported a patient who was diagnosed with adrenal failure (AHC; 300200) at 6 weeks of age, but who experienced transient recovery of adrenal function of several months' duration later in infancy. He subsequently failed to undergo puberty because of hypogonadotropic hypogonadism of pituitary origin, and he was also diagnosed with schizophrenia in early adulthood. Molecular genetic analyses revealed a complex rearrangement in DAX1, including a 2.2-kb deletion spanning the entire second exon and a small 27-bp insertion. The deletion extended from position 4561 through position 6801, completely eliminating exon 2 of the gene. The putative protein encoded by this mutated gene is 429 amino acids long. The initial 389 residues probably correspond to the wildtype DAX1 sequence, whereas the last 40 amino acids are presumably completely unrelated, being transcribed from the intronic sequence adjacent to exon 1. In vitro functional analyses confirmed the absence of repressor activity exerted by the mutant protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0027 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, TYR399TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894906,
|
|
|
|
|
|
|
|
ClinVar: RCV000011722
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the proband of a 5-generation Scottish kindred, 3 members of which had adrenal hypoplasia (300200), Brown et al. (2003) identified a C-to-A transversion in the second exon of the DAX1 gene that resulted in the change of tyr399 to a premature stop codon (Y399X), which truncates the DAX1 protein by 71 amino acids. Kindred analysis established that the mutation had been inherited from the proband's mother. The proband, his deceased brother, and a maternal cousin were hemizygous for the mutation. The mutation was associated with loss of Leydig cell responsiveness to human chorionic gonadotropin (see 118860); the 35-year-old proband exhibited hypogonadotropic hypogonadism. Immunohistochemical analysis of testicular tissue obtained from the proband's affected sib, who had died from adrenal failure as a neonate, showed normal testicular morphology and expression of DAX1, steroidogenic factor-1 (184757), and anti-mullerian hormone (600957). Transient transfection assays demonstrated that the mutation resulted in a severe loss of DAX1 repressor activity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0028 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, LEU297PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894907,
|
|
|
|
|
|
|
|
ClinVar: RCV000011723, RCV003764556
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In the 34-year-old male proband of an English kindred with adrenal hypoplasia and hypogonadotropic hypogonadism (300200), Brown et al. (2003) identified a T-to-C transition in exon 1 of the DAX1 gene, resulting in a leu297-to-pro amino acid change (L297P). Responsiveness to human chorionic gonadotropin (see 118860) was maintained. Kindred analysis established that the mutation had been inherited from the proband's mother. The L297P mutation occurred within a highly conserved binding motif (LLXLXL). Transient transfection assays demonstrated that the mutation resulted in a severe loss of DAX1 repressor activity. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0029 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, GLN37TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894908,
|
|
|
|
|
|
|
|
ClinVar: RCV000011724
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 20-year-old male with an unusual form of congenital adrenal hypoplasia (AHC; 300200) manifest as late-onset adrenal insufficiency and gonadal failure, Ozisik et al. (2003) demonstrated a C-to-T transition in the DAX1 gene that resulted in a gln37-to-ter (Q37X) substitution, predicted to cause severe truncation of the protein. Using a combination of in vitro translation assays and studies of DAX1 expression and function in transfected cells, they demonstrated that, in contrast to more distal mutations leading to a nonfunctional protein, this mutation is associated with a milder phenotype due to the expression of a partially functional, amino-truncated DAX1 protein generated from an alternate in-frame translation start site (methionine, codon 83). The production of this amino-truncated isoform appears to rescue the classical AHC phenotype, thereby delaying the onset of clinically significant adrenal dysfunction until early adulthood. Ozisik et al. (2003) concluded that this case demonstrated a relatively rare phenomenon by which the clinical severity of an inherited human disease is reduced after alternate translation from a site downstream of a premature stop codon. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0030 RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, TRP105CYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs132630327,
|
|
|
|
|
|
gnomAD: rs132630327,
|
|
|
|
|
|
ClinVar: RCV000011725, RCV002496328
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>This variant, formerly titled ISOLATED MINERALOCORTICOID DEFICIENCY, has been reclassified based on the findings of Verrijn Stuart et al. (2007). </p><p>In an 11-year-old prepubertal Dutch boy with a mild form of congenital adrenal hypoplasia (AHC; see 300200) involving prominent hypoaldosteronism without clear evidence of glucocorticoid insufficiency, Verrijn Stuart et al. (2007) identified a G-to-C transversion in the NR0B1 gene, resulting in a trp105-to-cys (W105C) substitution in the N terminus of DAX1. In vitro studies of DAX1 expression and function in transfected cells demonstrated mild loss of both repression and activation functions; structure-function analysis suggested that mutations in the N terminus are compensated by the presence of repeat LXXLL motifs that mediate DAX1 interactions with other proteins. An initial ACTH stimulation test in the proband revealed subnormal cortisol results; however, a second test showed normal cortisol values, and he did not experience adrenal crisis while on mineralocorticoid treatment only. The mutation, which was not found in 100 Dutch controls, was present in the proband's mother and was also detected in 3 asymptomatic male relatives. Verrijn Stuart et al. (2007) suggested that phenotypic heterogeneity might result from the effects of other genes that modify or compensate for NR0B1 function, or that environmental events or exposure to medications might unmask underlying adrenal dysfunction. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0031 ADRENAL HYPOPLASIA, CONGENITAL</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
NR0B1, TRP39TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1569269179,
|
|
|
|
|
|
|
|
ClinVar: RCV000239459
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 32-year-old male proband with adrenal insufficiency (AHC; 300200) who had been referred for infertility, Raffin-Sanson et al. (2013) detected hemizygosity for an A-to-G transition in the NR0B1 gene that resulted in substitution of a termination codon for trp39 (W39X). The mutation was also found in the proband's younger brother and nephew. The proband had been diagnosed with adrenal insufficiency at age 19 years and oligospermia at age 24 years. Biologic and hormonal explorations confirmed primary adrenal insufficiency, and computed tomography showed bilateral adrenal atrophy. Puberty had been spontaneous at age 13 years, with normal virilization, growth spurt, and testicular growth. Plasma total testosterone level remained normal throughout 25 years of follow-up, whereas oligospermia worsened over time. The patient fathered 1 child at age 33 through in vitro fertilization and another 2 years later after spontaneous conception. The proband's brother was normally virilized but had azoospermia and low testosterone; he exhibited an abnormal cortisol response to the standard-dose cortrosyn test, consistent with mild adrenal insufficiency. The proband's nephew had an adrenal crisis during the second week of life. He had normal testes and genitalia, but elevated plasma ACTH and renin levels confirmed primary adrenal insufficiency. Raffin-Sanson et al. (2013) stated that this was the first reported case of long-term preservation of gonadotrope function in a patient with markedly defective spermatogenesis due to an NR0B1 mutation, and concluded that the phenotypes of the proband, his brother, and his nephew illustrate the different possible adrenal consequences of identical NR0B1 mutations. </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">
|
|
Achermann, J. C., Gu, W.-X., Kotlar, T. J., Meeks, J. J., Sabacan, L. P., Seminara, S. B., Habiby, R. L., Hindmarsh, P. C., Bick, D. P., Sherins, R. J., Crowley, W. F., Jr., Layman, L. C., Jameson, J. L.
|
|
<strong>Mutational analysis of DAX1 in patients with hypogonadotropic hypogonadism or pubertal delay.</strong>
|
|
J. Clin. Endocr. Metab. 84: 4497-4500, 1999.
|
|
|
|
|
|
[PubMed: 10599708]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.84.12.6269]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Achermann, J. C., Ito, M., Ito, M., Hindmarsh, P. C., Jameson, J. L.
|
|
<strong>A mutation in the gene encoding steroidogenic factor-1 causes XY sex reversal and adrenal failure in humans. (Letter)</strong>
|
|
Nature Genet. 22: 125-126, 1999.
|
|
|
|
|
|
[PubMed: 10369247]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/9629]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Achermann, J. C., Silverman, B. L., Habiby, R. L., Jameson, J. L.
|
|
<strong>Presymptomatic diagnosis of X-linked adrenal hypoplasia congenita by analysis of DAX1.</strong>
|
|
J. Pediat. 137: 878-881, 2000.
|
|
|
|
|
|
[PubMed: 11113848]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1067/mpd.2000.108567]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bardoni, B., Zanaria, E., Guioli, S., Floridia, G., Worley, K. C., Tonini, G., Ferrante, E., Chiumello, G., McCabe, E. R. B., Fraccaro, M., Zuffardi, O., Camerino, G.
|
|
<strong>A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal.</strong>
|
|
Nature Genet. 7: 497-501, 1994.
|
|
|
|
|
|
[PubMed: 7951319]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0894-497]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brown, P., Scobie, G. A., Townsend, J., Bayne, R. A. L., Seckl, J. R., Saunders, P. T. K., Anderson, R. A.
|
|
<strong>Identification of a novel missense mutation that is as damaging to DAX-1 repressor function as a nonsense mutation.</strong>
|
|
J. Clin. Endocr. Metab. 88: 1341-1349, 2003.
|
|
|
|
|
|
[PubMed: 12629128]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2002-021560]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Calvo, R. M., Asuncion, M., Telleria, D., Sancho, J., San Millan, J. L., Escobar-Morreale, H. F.
|
|
<strong>Screening for mutations in the steroidogenic acute regulatory protein and steroidogenic factor-1 genes, and in CYP11A and dosage-sensitive sex reversal-adrenal hypoplasia gene on the X chromosome, gene-1 (DAX-1), in hyperandrogenic hirsute women.</strong>
|
|
J. Clin. Endocr. Metab. 86: 1746-1749, 2001.
|
|
|
|
|
|
[PubMed: 11297612]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.86.4.7424]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Caron, P., Imbeaud, S., Bennet, A., Plantavid, M., Camerino, G., Rochiccioli, P.
|
|
<strong>Combined hypothalamic-pituitary-gonadal defect in a hypogonadic man with a novel mutation in the DAX-1 gene.</strong>
|
|
J. Clin. Endocr. Metab. 84: 3563-3569, 1999.
|
|
|
|
|
|
[PubMed: 10522996]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.84.10.6030]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Domenice, S., Latronico, A. C., Brito, V. N., Arnhold, I. J. P., Kok, F., Mendonca, B. B.
|
|
<strong>Adrenocorticotropin-dependent precocious puberty of testicular origin in a boy with X-linked adrenal hypoplasia congenita due to a novel mutation in the DAX1 gene.</strong>
|
|
J. Clin. Endocr. Metab. 86: 4068-4071, 2001.
|
|
|
|
|
|
[PubMed: 11549627]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.86.9.7816]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Guo, W., Burris, T. P., McCabe, E. R. B.
|
|
<strong>Expression of DAX-1, the gene responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism, in the hypothalamic-pituitary-adrenal/gonadal axis.</strong>
|
|
Biochem. Molec. Med. 56: 8-13, 1995.
|
|
|
|
|
|
[PubMed: 8593542]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bmme.1995.1049]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Guo, W., Burris, T. P., Zhang, Y.-H., Huang, B.-L., Mason, J., Copeland, K. C., Kupfer, S. R., Pagon, R. A., McCabe, E. R. B.
|
|
<strong>Genomic sequence of the DAX1 gene: an orphan nuclear receptor responsible for X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.</strong>
|
|
J. Clin. Endocr. Metab. 81: 2481-2486, 1996.
|
|
|
|
|
|
[PubMed: 8675564]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.81.7.8675564]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Guo, W., Lovell, R. S., Zhang, Y.-H., Huang, B.-L., Burris, T. P., Craigen, W. J., McCabe, E. R. B.
|
|
<strong>Ahch, the mouse homologue of DAX1: cloning, characterization and synteny with GyK, the glycerol kinase locus.</strong>
|
|
Gene 178: 31-34, 1996.
|
|
|
|
|
|
[PubMed: 8921887]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0378-1119(96)00320-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Habiby, R. L., Boepple, P., Nachtigall, L., Sluss, P. M., Crowley, W. F., Jr., Jameson, J. L.
|
|
<strong>Adrenal hypoplasia congenita with hypogonadotropic hypogonadism: evidence that DAX-1 mutations lead to combined hypothalamic and pituitary defects in gonadotropin production.</strong>
|
|
J. Clin. Invest. 98: 1055-1062, 1996.
|
|
|
|
|
|
[PubMed: 8770879]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI118866]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ho, J., Zhang, Y.-H., Huang, B.-L., McCabe, E. R. B.
|
|
<strong>NR0B1A: an alternatively spliced form of NR0B1.</strong>
|
|
Molec. Genet. Metab. 83: 330-336, 2004.
|
|
|
|
|
|
[PubMed: 15589120]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2004.10.002]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hossain, A., Li, C., Saunders, G. F.
|
|
<strong>Generation of two distinct functional isoforms of dosage-sensitive sex reversal-adrenal hypoplasia congenita-critical region on the X chromosome gene 1 (DAX-1) by alternative splicing.</strong>
|
|
Molec. Endocr. 18: 1428-1437, 2004.
|
|
|
|
|
|
[PubMed: 15044589]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/me.2003-0176]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Iyer, A. K., Zhang, Y.-H., McCabe, E. R. B.
|
|
<strong>Dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1) (NR0B1) and small heterodimer partner (SHP) (NR0B2) form homodimers individually, as well as DAX1-SHP heterodimers.</strong>
|
|
Molec. Endocr. 20: 2326-2342, 2006.
|
|
|
|
|
|
[PubMed: 16709599]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/me.2005-0383]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Iyer, A. K., Zhang, Y.-H., McCabe, E. R. B.
|
|
<strong>LXXLL motifs and AF-2 domain mediate SHP (NR0B2) homodimerization and DAX1 (NR0B1)-DAX1A heterodimerization.</strong>
|
|
Molec. Genet. Metab. 92: 151-159, 2007.
|
|
|
|
|
|
[PubMed: 17686645]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2007.06.009]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kang, Y., Zheng, B., Shen, B., Chen, Y., Wang, L., Wang, J., Niu, Y., Cui, Y., Zhou, J., Wang, H., Guo, X., Hu, B., Zhou, Q., Sha, J., Ji, W., Huang, X.
|
|
<strong>CRISPR/Cas9-mediated Dax1 knockout in the monkey recapitulates human AHC-HH.</strong>
|
|
Hum. Molec. Genet. 24: 7255-7264, 2015.
|
|
|
|
|
|
[PubMed: 26464492]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddv425]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kojima, Y., Sasaki, S., Hayashi, Y., Umemoto, Y., Morohashi, K.-I., Kohri, K.
|
|
<strong>Role of transcription factors Ad4BP/SF-1 and DAX-1 in steroidogenesis and spermatogenesis in human testicular development and idiopathic azoospermia.</strong>
|
|
Int. J. Urol. 13: 785-793, 2006.
|
|
|
|
|
|
[PubMed: 16834661]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1442-2042.2006.01403.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lalli, E., Bardoni, B., Zazopoulos, E., Wurtz, J.-M., Strom, T. M., Moras, D., Sassone-Corsi, P.
|
|
<strong>A transcriptional silencing domain in DAX-1 whose mutation causes adrenal hypoplasia congenita.</strong>
|
|
Molec. Endocr. 11: 1950-1960, 1997.
|
|
|
|
|
|
[PubMed: 9415399]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/mend.11.13.0038]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lalli, E., Ohe, K., Hindelang, C., Sassone-Corsi, P.
|
|
<strong>Orphan receptor DAX-1 is a shuttling RNA binding protein associated with polyribosomes via mRNA.</strong>
|
|
Molec. Cell. Biol. 20: 4910-4921, 2000.
|
|
|
|
|
|
[PubMed: 10848616]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.20.13.4910-4921.2000]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lehmann, S. G., Lalli, E., Sassone-Corsi, P.
|
|
<strong>X-linked adrenal hypoplasia congenita is caused by abnormal nuclear localization of the DAX-1 protein.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 8225-8230, 2002.
|
|
|
|
|
|
[PubMed: 12034880]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.122044099]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lehmann, S. G., Wurtz, J.-M., Renaud, J.-P., Sassone-Corsi, P., Lalli, E.
|
|
<strong>Structure-function analysis reveals the molecular determinants of the impaired biological function of DAX-1 mutants in AHC patients.</strong>
|
|
Hum. Molec. Genet. 12: 1063-1072, 2003.
|
|
|
|
|
|
[PubMed: 12700175]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg108]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lin, L., Gu, W.-X., Ozisik, G., To, W. S., Owen, C. J., Jameson, J. L., Achermann, J. C.
|
|
<strong>Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (NR5A1) in children and adults with primary adrenal failure: ten years' experience.</strong>
|
|
J. Clin. Endocr. Metab. 91: 3048-3054, 2006.
|
|
|
|
|
|
[PubMed: 16684822]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2006-0603]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Luo, X., Ikeda, Y., Parker, K. L.
|
|
<strong>A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation.</strong>
|
|
Cell 77: 481-490, 1994.
|
|
|
|
|
|
[PubMed: 8187173]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(94)90211-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mantovani, G., Ozisik, G., Achermann, J. C., Romoli, R., Borretta, G., Persani, L., Spada, A., Jameson, J. L., Beck-Peccoz, P.
|
|
<strong>Hypogonadotropic hypogonadism as a presenting feature of late-onset X-linked adrenal hypoplasia congenital.</strong>
|
|
J. Clin. Endocr. Metab. 87: 44-48, 2002.
|
|
|
|
|
|
[PubMed: 11788621]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.87.1.8163]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McCabe, E. R. B.
|
|
<strong>Sex and the single DAX1: too little is bad, but can we have too much? (Editorial)</strong>
|
|
J. Clin. Invest. 98: 881-882, 1996.
|
|
|
|
|
|
[PubMed: 8770856]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI118868]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meeks, J. J., Weiss, J., Jameson, J. L.
|
|
<strong>Dax1 is required for testis determination.</strong>
|
|
Nature Genet. 34: 32-33, 2003.
|
|
|
|
|
|
[PubMed: 12679814]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1141]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Merke, D. P., Tajima, T., Baron, J., Cutler, G. B., Jr.
|
|
<strong>Hypogonadotropic hypogonadism in a female caused by an X-linked recessive mutation in the DAX1 gene.</strong>
|
|
New Eng. J. Med. 340: 1248-1252, 1999.
|
|
|
|
|
|
[PubMed: 10210708]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199904223401605]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Muscatelli, F., Strom, T. M., Walker, A. P., Zanaria, E., Recan, D., Meindl, A., Bardoni, B., Guioli, S., Zehetner, G., Rabl, W., Schwarz, H. P., Kaplan, J.-C., Camerino, G., Meitinger, T., Monaco, A. P.
|
|
<strong>Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism.</strong>
|
|
Nature 372: 672-676, 1994.
|
|
|
|
|
|
[PubMed: 7990958]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/372672a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nachtigal, M. W., Hirokawa, Y., Enyeart-VanHouten, D. L., Flanagan, J. N., Hammer, G. D., Ingraham, H. A.
|
|
<strong>Wilms' tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression.</strong>
|
|
Cell 93: 445-454, 1998.
|
|
|
|
|
|
[PubMed: 9590178]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)81172-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nakae, J., Abe, S., Tajima, T., Shinohara, N., Murashita, M., Igarashi, Y., Kusuda, S., Suzuki, J., Fujieda, K.
|
|
<strong>Three novel mutations and a de novo deletion mutation of the DAX-1 gene in patients with X-linked adrenal hypoplasia congenita.</strong>
|
|
J. Clin. Endocr. Metab. 82: 3835-3841, 1997.
|
|
|
|
|
|
[PubMed: 9360549]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.82.11.4342]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nakae, J., Tajima, T., Kusuda, S., Kohda, N., Okabe, T., Shinohara, N., Kato, M., Murashita, M., Mukai, T., Imanaka, K., Fujieda, K.
|
|
<strong>Truncation at the C-terminus of the DAX-1 protein impairs its biological actions in patients with X-linked adrenal hypoplasia congenita.</strong>
|
|
J. Clin. Endocr. Metab. 81: 3680-3685, 1996.
|
|
|
|
|
|
[PubMed: 8855822]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.81.10.8855822]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Niakan, K. K., McCabe, E. R. B.
|
|
<strong>DAX1 origin, function, and novel role.</strong>
|
|
Molec. Genet. Metab. 86: 70-83, 2005.
|
|
|
|
|
|
[PubMed: 16146703]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2005.07.019]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ozisik, G., Mantovani, G., Achermann, J. C., Persani, L., Spada, A., Weiss, J., Beck-Peccoz, P., Jameson, J. L.
|
|
<strong>An alternate translation initiation site circumvents an amino-terminal DAX1 nonsense mutation leading to a mild form of X-linked adrenal hypoplasia congenita.</strong>
|
|
J. Clin. Endocr. Metab. 88: 417-423, 2003.
|
|
|
|
|
|
[PubMed: 12519885]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2002-021034]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Peter, M., Viemann, M., Partsch, C.-J., Sippell, W. G.
|
|
<strong>Congenital adrenal hypoplasia: clinical spectrum, experience with hormonal diagnosis, and report on new point mutations of the DAX-1 gene.</strong>
|
|
J. Clin. Endocr. Metab. 83: 2666-2674, 1998.
|
|
|
|
|
|
[PubMed: 9709929]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.83.8.5027]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Petersen, K. E., Bille, T., Jacobsen, B. B., Iversen, T.
|
|
<strong>X-linked congenital adrenal hypoplasia: a study of five generations of a Greenlandic family.</strong>
|
|
Acta Paediat. Scand. 71: 947-951, 1982.
|
|
|
|
|
|
[PubMed: 6891556]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1651-2227.1982.tb09554.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Phelan, J. K., McCabe, E. R. B.
|
|
<strong>Mutations in NR0B1 (DAX1) and NR5A1 (SF1) responsible for adrenal hypoplasia congenita.</strong>
|
|
Hum. Mutat. 18: 472-487, 2001.
|
|
|
|
|
|
[PubMed: 11748841]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1225]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Raffin-Sanson, M.-L., Oudet, B., Salenave, S., Brailly-Tabard, S., Pehuet, M., Christin-Maitre, S., Morel, Y., Young, J.
|
|
<strong>A man with a DAX1/NR0B1 mutation, normal puberty, and an intact hypothalamic-pituitary-gonadal axis but deteriorating oligospermia during long-term follow-up.</strong>
|
|
Europ. J. Endocr. 168: K45-K50, 2013.
|
|
|
|
|
|
[PubMed: 23384712]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1530/EJE-12-1055]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reincke, M., Beuschlein, F., Lalli, E., Arlt, W., Vay, S., Sassone-Corsi, P., Allolio, B.
|
|
<strong>DAX-1 expression in human adrenocortical neoplasms: implications for steroidogenesis.</strong>
|
|
J. Clin. Endocr. Metab. 83: 2597-2600, 1998.
|
|
|
|
|
|
[PubMed: 9661652]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.83.7.5095]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Salvi, R., Gomez, F., Fiaux, M., Schorderet, D., Jameson, J. L., Achermann, J. C., Gaillard, R. C., Pralong, F. P.
|
|
<strong>Progressive onset of adrenal insufficiency and hypogonadism of pituitary origin caused by a complex genetic rearrangement within DAX-1.</strong>
|
|
J. Clin. Endocr. Metab. 87: 4094-4100, 2002.
|
|
|
|
|
|
[PubMed: 12213854]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2001-011930]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schwartz, M., Blichfeldt, S., Muller, J.
|
|
<strong>X-linked adrenal hypoplasia in a large Greenlandic family. Detection of a missense mutation (N4401) in the DAX-1 gene; implication for genetic counselling and carrier diagnosis.</strong>
|
|
Hum. Genet. 99: 83-87, 1997.
|
|
|
|
|
|
[PubMed: 9003500]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050316]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Seminara, S. B., Achermann, J. C., Genel, M., Jameson, J. L., Crowley, W. F., Jr.
|
|
<strong>X-linked adrenal hypoplasia congenita: a mutation in DAX1 expands the phenotypic spectrum in males and females.</strong>
|
|
J. Clin. Endocr. Metab. 84: 4501-4509, 1999.
|
|
|
|
|
|
[PubMed: 10599709]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.84.12.6172]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Swain, A., Narvaez, V., Burgoyne, P., Camerino, G., Lovell-Badge, R.
|
|
<strong>Dax1 antagonizes Sry action in mammalian sex determination.</strong>
|
|
Nature 391: 761-767, 1998.
|
|
|
|
|
|
[PubMed: 9486644]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/35799]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Swain, A., Zanaria, E., Hacker, A., Lovell-Badge, R., Camerino, G.
|
|
<strong>Mouse Dax1 expression is consistent with a role in sex determination as well as in adrenal and hypothalamus function.</strong>
|
|
Nature Genet. 12: 404-409, 1996.
|
|
|
|
|
|
[PubMed: 8630494]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0496-404]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tabarin, A., Achermann, J. C., Recan, D., Bex, V., Bertagna, X., Christin-Maitre, S., Ito, M., Jameson, J. L., Bouchard, P.
|
|
<strong>A novel mutation in DAX1 causes delayed-onset adrenal insufficiency and incomplete hypogonadotropic hypogonadism.</strong>
|
|
J. Clin. Invest. 105: 321-328, 2000.
|
|
|
|
|
|
[PubMed: 10675358]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1172/JCI7212]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Takayanagi, R., Okabe, T., Sakai, O., Nawata, H., Kato, K., Ibayashi, H.
|
|
<strong>A case of congenital adrenal hypoplasia and hypogonadism.</strong>
|
|
Horumon To Rinsho 40: 81-84, 1992.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tamai, K. T., Monaco, L., Alastalo, T.-P., Lalli, E., Parvinen, M., Sassone-Corsi, P.
|
|
<strong>Hormonal and developmental regulation of DAX-1 expression in Sertoli cells.</strong>
|
|
Molec. Endocr. 10: 1561-1569, 1996.
|
|
|
|
|
|
[PubMed: 8961266]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/mend.10.12.8961266]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Telvi, L., Ion, A., Carel, J.-C., Desguerre, I., Piraud, M., Boutin, A. M., Feingold, J., Ponsot, G., Fellous, M., McElreavey, K.
|
|
<strong>A duplication of distal Xp associated with hypogonadotrophic hypogonadism, hypoplastic external genitalia, mental retardation, and multiple congenital abnormalities.</strong>
|
|
J. Med. Genet. 33: 767-771, 1996.
|
|
|
|
|
|
[PubMed: 8880579]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.33.9.767]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Verrijn Stuart, A. A., Ozisik, G., de Vroede, M. A., Giltay, J. C., Sinke, R. J., Peterson, T. J., Harris, R. M., Weiss, J., Jameson, J. L.
|
|
<strong>An amino-terminal DAX1 (NR0B1) missense mutation associated with isolated mineralocorticoid deficiency.</strong>
|
|
J. Clin. Endocr. Metab. 92: 755-761, 2007.
|
|
|
|
|
|
[PubMed: 17164309]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2005-2429]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, J., Killinger, D. W., Hegele, R. A.
|
|
<strong>A microdeletion within DAX-1 in X-linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism.</strong>
|
|
J. Investig. Med. 47: 232-235, 1999.
|
|
|
|
|
|
[PubMed: 10361383]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yanase, T., Takayanagi, R., Oba, K., Nishi, Y., Ohe, K., Nawata, H.
|
|
<strong>New mutations of DAX-1 genes in two Japanese patients with X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism.</strong>
|
|
J. Clin. Endocr. Metab. 81: 530-535, 1996.
|
|
|
|
|
|
[PubMed: 8636263]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.81.2.8636263]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yu, R. N., Ito, M., Saunders, T. L., Camper, S. A., Jameson, J. L.
|
|
<strong>Role of Ahch in gonadal development and gametogenesis.</strong>
|
|
Nature Genet. 20: 353-357, 1998.
|
|
|
|
|
|
[PubMed: 9843206]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/3822]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zanaria, E., Muscatelli, F., Bardoni, B., Strom, T. M., Guioli, S., Guo, W., Lalli, E., Moser, C., Walker, A. P., McCabe, E. R. B., Meitinger, T., Monaco, A. P., Sassone-Corsi, P., Camerino, G.
|
|
<strong>An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita.</strong>
|
|
Nature 372: 635-641, 1994.
|
|
|
|
|
|
[PubMed: 7990953]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/372635a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zazopoulos, E., Lalli, E., Stocco, D. M., Sassone-Corsi, P.
|
|
<strong>DNA binding and transcriptional repression by DAX-1 blocks steroidogenesis.</strong>
|
|
Nature 390: 311-315, 1997.
|
|
|
|
|
|
[PubMed: 9384387]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/36899]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, Y.-H., Guo, W., Wagner, R. L., Huang, B.-L., McCabe, L., Vilain, E., Burris, T. P., Anyane-Yeboa, K., Burghes, A. H. M., Chitayat, D., Chudley, A. E., Genel, M., and 12 others.
|
|
<strong>DAX1 mutations map to putative structural domains in a deduced three-dimensional model.</strong>
|
|
Am. J. Hum. Genet. 62: 855-864, 1998.
|
|
|
|
|
|
[PubMed: 9529340]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/301782]
|
|
|
|
|
|
</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">
|
|
Patricia A. Hartz - updated : 09/22/2016<br>Marla J. F. O'Neill - updated : 08/09/2016<br>Marla J. F. O'Neill - updated : 6/29/2010<br>Patricia A. Hartz - updated : 10/29/2009<br>Marla J. F. O'Neill - updated : 9/16/2009<br>John A. Phillips, III - updated : 1/28/2008<br>Marla J. F. O'Neill - updated : 7/26/2006<br>George E. Tiller - updated : 12/20/2004<br>John A. Phillips, III - updated : 7/20/2004<br>John A. Phillips, III - updated : 3/29/2004
|
|
</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">
|
|
Cassandra L. Kniffin : 1/29/2004
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
mgross : 09/22/2016<br>alopez : 08/10/2016<br>alopez : 08/09/2016<br>carol : 07/28/2015<br>joanna : 9/18/2012<br>terry : 4/12/2012<br>terry : 3/15/2011<br>terry : 3/15/2011<br>alopez : 3/1/2011<br>carol : 6/29/2010<br>carol : 2/1/2010<br>carol : 1/29/2010<br>mgross : 11/4/2009<br>terry : 10/29/2009<br>carol : 10/5/2009<br>terry : 9/16/2009<br>terry : 9/16/2009<br>carol : 4/7/2009<br>terry : 3/4/2009<br>terry : 9/26/2008<br>wwang : 4/29/2008<br>wwang : 3/26/2008<br>carol : 1/28/2008<br>terry : 8/9/2007<br>carol : 7/27/2006<br>terry : 7/26/2006<br>tkritzer : 12/20/2004<br>carol : 10/12/2004<br>alopez : 7/20/2004<br>alopez : 3/29/2004<br>carol : 2/23/2004<br>ckniffin : 2/5/2004
|
|
</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>
|
|
|
|
|