1962 lines
136 KiB
Text
1962 lines
136 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
|
|
|
|
- #300815 - CHROMOSOME Xq28 DUPLICATION SYNDROME
|
|
|
|
|
|
- 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=300815"><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">#300815</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="#clinicalFeatures">Clinical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cytogenetics">Cytogenetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</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="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" 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 in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://clinicaltrials.gov/search?cond=CHROMOSOME Xq28 DUPLICATION SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>EuroGentest</div>
|
|
<div id="mimEuroGentestFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=1190&Typ=Pat" title="Proximal Xq28 duplication syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Proximal Xq28 duplication … </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=20892&Typ=Pat" title="Distal Xq28 microduplication syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Distal Xq28 microduplicati… </a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK349624/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=300815[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><a href="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Orphanet</div>
|
|
<div id="mimOrphanetFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1762" title="Proximal Xq28 duplication syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Proximal Xq28 duplication …</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=293939" title="Distal Xq28 microduplication syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Distal Xq28 microduplicati…</a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/b58af04f-49e7-4913-9f45-cc01d588fb97/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</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>ORPHA:</strong> 1762, 293939<br />
|
|
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
|
|
<span class="text-danger"><strong>#</strong></span>
|
|
300815
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
CHROMOSOME Xq28 DUPLICATION SYNDROME
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/X/771?start=-3&limit=10&highlight=771">Xq28</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chrX:148000001-156040895&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:148,000,001-156,040,895</a> </span>
|
|
</em>
|
|
</strong>
|
|
|
|
|
|
|
|
|
|
</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
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/X/771?start=-3&limit=10&highlight=771">
|
|
Xq28
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Chromosome Xq28 duplication syndrome
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/300815"> 300815 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="4 - A contiguous gene duplication or deletion syndrome in which multiple genes are involved">4</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
|
|
<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 id="mimTextFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because this disorder is caused by copy number increase of a small region on distal chromosome Xq28. One report has identified a 0.3-Mb region of Xq28 (chrX:153.2-153.5 Mb, NCBI36) containing at least 11 genes and including the GDI1 gene (<a href="/entry/300104">300104</a>), which is mutated in MRX41 (<a href="/entry/300849">300849</a>). Two additional reports have identified a more distal 0.5-Mb region (chrX:153.7-154.2 Mb (NCBI36/hg19)) containing at least 8 genes and including the RAB39B gene (<a href="/entry/300774">300774</a>), which is mutated in MRX72 (<a href="/entry/300271">300271</a>).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="clinicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#5" class="mim-tip-reference" title="Vandewalle, J., Van Esch, H., Govaerts, K., Verbeeck, J., Zweir, C., Madrigal, I., Mila, M., Pijkels, E., Fernandez, I., Kohlase, J., Spaich, C., Rauch, A., Fryns, J.-P., Marynen, P., Froyen, G. <strong>Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination.</strong> Am. J. Hum. Genet. 85: 809-822, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20004760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20004760</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20004760[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.ajhg.2009.10.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20004760">Vandewalle et al. (2009)</a> reported 4 families with X-linked mental retardation. The first family was of Belgian origin and had 4 affected males in 2 generations. All had normal growth, moderate mental retardation, and variable mild dysmorphic features, including mild 2-3 toe syndactyly, ataxic gait, and strabismus. The second family was of German origin and consisted of 2 affected brothers. The older brother was of average gestational size but was very floppy and was found to have a classic Dandy-Walker malformation, with cerebellar hypoplasia and agenesis of the corpus callosum. He developed seizures at 15 months of age and was microcephalic. Dysmorphic features included large ears, upslanting palpebral fissures, epicanthal folds, and thin lips. His brother also had a Dandy-Walker malformation, with agenesis of the cerebellar vermis and hypoplasia of the corpus callosum. At 19 months he had not developed seizures but had microcephaly. The third family reported by <a href="#5" class="mim-tip-reference" title="Vandewalle, J., Van Esch, H., Govaerts, K., Verbeeck, J., Zweir, C., Madrigal, I., Mila, M., Pijkels, E., Fernandez, I., Kohlase, J., Spaich, C., Rauch, A., Fryns, J.-P., Marynen, P., Froyen, G. <strong>Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination.</strong> Am. J. Hum. Genet. 85: 809-822, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20004760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20004760</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20004760[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.ajhg.2009.10.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20004760">Vandewalle et al. (2009)</a> was of Spanish origin and was reported as case 6 by <a href="#4" class="mim-tip-reference" title="Madrigal, I., Rodriguez-Revenga, L., Armengol, L., Gonzalez, E., Rodriguez, B., Badenas, C., Sanchez, A., Martinez, F., Guitart, M., Fernandez-Carvajal, I., Arranz, J. A., Tejada, M. I., Perez-Jurado, L. A., Estivill, X., Mila, M. <strong>X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation.</strong> BMC Genomics 8: 443, 2007. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18047645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18047645</a>] [<a href="https://doi.org/10.1186/1471-2164-8-443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18047645">Madrigal et al. (2007)</a>. The index case was born to nonconsanguineous parents at 8 months of pregnancy complicated by an acute pancreatitis. He developed neonatal seizures and cyanotic crises, and was hospitalized for 10 days. Imaging of his brain showed ventricular dilatation and large asymmetric cisterna magna. Gross motor milestones were within normal range. His speech development was delayed. At age 7, he had mild dysmorphic features with microcephaly, a high palate, medial eyebrow flare, and prominent ears. His IQ was 58. Neurologic examination was normal. No clinical details were available for 2 maternal brothers who were institutionalized. The fourth family was a sporadic case born to healthy, unrelated German parents. He had mild global psychomotor delay and did not begin walking until 20 months of age. Mild dysmorphic features were present, including brachycephaly, broad forehead, hypotelorism, and epicanthus inversus, more pronounced at the left side. He had a rather flat midface with flat nasal root and a short philtrum. He had a high palate and a small chin. Head circumference was at the 25th percentile. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18047645+20004760" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 addition to mental retardation and dysmorphic features, <a href="#5" class="mim-tip-reference" title="Vandewalle, J., Van Esch, H., Govaerts, K., Verbeeck, J., Zweir, C., Madrigal, I., Mila, M., Pijkels, E., Fernandez, I., Kohlase, J., Spaich, C., Rauch, A., Fryns, J.-P., Marynen, P., Froyen, G. <strong>Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination.</strong> Am. J. Hum. Genet. 85: 809-822, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20004760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20004760</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20004760[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.ajhg.2009.10.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20004760">Vandewalle et al. (2009)</a> found ventricular aberrations in 2 families. A large fourth ventricle was seen in family 1, and a ventricular dilatation in family 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20004760" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="cytogenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimCytogeneticsFold" id="mimCytogeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCytogeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cytogenetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCytogeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#1" class="mim-tip-reference" title="El-Hattab, A. W., Fang, P., Jin, W., Hughes, J. R., Gibson, J. B., Patel, G. S., Grange, D. K., Manwaring, L. P., Patel, A., Stankiewicz, P., Cheung, S. W. <strong>Int22h-1/int22h-2-mediated Xq28 rearrangements: intellectual disability associated with duplications and in utero male lethality with deletions.</strong> J. Med. Genet. 48: 840-850, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21984752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21984752</a>] [<a href="https://doi.org/10.1136/jmedgenet-2011-100125" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21984752">El-Hattab et al. (2011)</a> reported 4 boys, including 2 brothers, with intellectual disability and behavioral disorders associated with a recurrent approximately 0.5-Mb duplication of chromosome Xq28 identified through array CGH. The duplications spanned chrX:153.7-154.2 Mb (NCBI36/hg19), and were confirmed by FISH analysis. All 3 mothers, who were more mildly affected with learning difficulties, also carried the duplication. X-chromosome inactivation studies showed skewed patterns in all 3 of the mothers, 2 with preferential inactivation of the normal chromosome and 1 with preferential inactivation of the duplicated chromosome. DNA sequence analysis showed that the breakpoints occurred within the directly oriented low-copy repeat (LCR) regions int22h-1 and int22h-2, which are in or close to the F8 gene (<a href="/entry/300841">300841</a>). The duplicated region contained 9 genes, including RAB39B (<a href="/entry/300774">300774</a>), but not GDI1 (<a href="/entry/300104">300104</a>). All 4 boys with the duplication had cognitive impairment, aggressive and/or hyperactive behavior, recurrent ear infections or pneumonia, and mildly dysmorphic facial features, including high forehead, upper eyelid fullness, broad nasal bridge, and thick lower lip. A mother and daughter from a fourth family were found to carry a heterozygous reciprocal deletion of Xq28 with 100% skewed X-chromosome inactivation of the chromosome with the deletion. Neither had intellectual disability, but the daughter came to attention for hyperactivity, inattentiveness, and sensory integration difficulties. The mother had a history of 2 spontaneous abortions, which <a href="#1" class="mim-tip-reference" title="El-Hattab, A. W., Fang, P., Jin, W., Hughes, J. R., Gibson, J. B., Patel, G. S., Grange, D. K., Manwaring, L. P., Patel, A., Stankiewicz, P., Cheung, S. W. <strong>Int22h-1/int22h-2-mediated Xq28 rearrangements: intellectual disability associated with duplications and in utero male lethality with deletions.</strong> J. Med. Genet. 48: 840-850, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21984752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21984752</a>] [<a href="https://doi.org/10.1136/jmedgenet-2011-100125" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21984752">El-Hattab et al. (2011)</a> postulated may indicate that the deletion is lethal to males in utero. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21984752" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Vanmarsenille, L., Giannandrea, M., Fieremans, N., Verbeeck, J., Belet, S., Raynaud, M., Vogels, A., Mannik, K., Ounap, K., Jacqueline, V., Briault, S., Van Esch, H., D'Adamo, P., Froyen, G. <strong>Increased dosage of RAB39B affects neuronal development and could explain the cognitive impairment in male patients with distal Xq28 copy number gains.</strong> Hum. Mutat. 35: 377-383, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24357492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24357492</a>] [<a href="https://doi.org/10.1002/humu.22497" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24357492">Vanmarsenille et al. (2014)</a> reported 4 male patients, including 2 brothers, with intellectual disability associated with a recurrent approximately 0.5-Mb duplication at distal chromosome Xq28 (chrX: 154.1-154.6 (hg19)). The duplications were apparently the same as those reported by <a href="#1" class="mim-tip-reference" title="El-Hattab, A. W., Fang, P., Jin, W., Hughes, J. R., Gibson, J. B., Patel, G. S., Grange, D. K., Manwaring, L. P., Patel, A., Stankiewicz, P., Cheung, S. W. <strong>Int22h-1/int22h-2-mediated Xq28 rearrangements: intellectual disability associated with duplications and in utero male lethality with deletions.</strong> J. Med. Genet. 48: 840-850, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21984752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21984752</a>] [<a href="https://doi.org/10.1136/jmedgenet-2011-100125" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21984752">El-Hattab et al. (2011)</a>, and the breakpoints involved the int22h-1 and int22h-2 LCRs. The duplicated region was distal to and did not include the GDI1 gene. Cell lines from 2 of the patients showed increased mRNA expression of BRCC3 (<a href="/entry/300617">300617</a>), VBP1 (<a href="/entry/300133">300133</a>), and RAB39B. The patients had behavioral or psychiatric problems, including schizophrenia in 1, and variable dysmorphic features, such as high forehead, large ears, deep-set eyes, and thin upper lip. <a href="#6" class="mim-tip-reference" title="Vanmarsenille, L., Giannandrea, M., Fieremans, N., Verbeeck, J., Belet, S., Raynaud, M., Vogels, A., Mannik, K., Ounap, K., Jacqueline, V., Briault, S., Van Esch, H., D'Adamo, P., Froyen, G. <strong>Increased dosage of RAB39B affects neuronal development and could explain the cognitive impairment in male patients with distal Xq28 copy number gains.</strong> Hum. Mutat. 35: 377-383, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24357492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24357492</a>] [<a href="https://doi.org/10.1002/humu.22497" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24357492">Vanmarsenille et al. (2014)</a> noted that point mutations in the RAB39B gene can cause X-linked mental retardation-72 (MRX72; <a href="/entry/300271">300271</a>). Overexpression of Rab39b in mouse primary hippocampal neurons resulted in a significant decrease in neuronal branching as well as a decrease in the number of synapses compared to controls. These findings led <a href="#6" class="mim-tip-reference" title="Vanmarsenille, L., Giannandrea, M., Fieremans, N., Verbeeck, J., Belet, S., Raynaud, M., Vogels, A., Mannik, K., Ounap, K., Jacqueline, V., Briault, S., Van Esch, H., D'Adamo, P., Froyen, G. <strong>Increased dosage of RAB39B affects neuronal development and could explain the cognitive impairment in male patients with distal Xq28 copy number gains.</strong> Hum. Mutat. 35: 377-383, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24357492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24357492</a>] [<a href="https://doi.org/10.1002/humu.22497" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24357492">Vanmarsenille et al. (2014)</a> to conclude that increased dosage of the RAB39B gene causes disturbed neuronal development leading to cognitive impairment. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21984752+24357492" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>In 4 families with X-linked mental retardation, <a href="#5" class="mim-tip-reference" title="Vandewalle, J., Van Esch, H., Govaerts, K., Verbeeck, J., Zweir, C., Madrigal, I., Mila, M., Pijkels, E., Fernandez, I., Kohlase, J., Spaich, C., Rauch, A., Fryns, J.-P., Marynen, P., Froyen, G. <strong>Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination.</strong> Am. J. Hum. Genet. 85: 809-822, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20004760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20004760</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20004760[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.ajhg.2009.10.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20004760">Vandewalle et al. (2009)</a> identified copy number gain of an identical 0.3-Mb region at chromosome Xq28 that included 18 annotated genes. Of these, RPL10 (<a href="/entry/312173">312173</a>), ATP6AP1 (<a href="/entry/300197">300197</a>), and GDI1 (<a href="/entry/300104">300104</a>) are expressed in brain. <a href="#5" class="mim-tip-reference" title="Vandewalle, J., Van Esch, H., Govaerts, K., Verbeeck, J., Zweir, C., Madrigal, I., Mila, M., Pijkels, E., Fernandez, I., Kohlase, J., Spaich, C., Rauch, A., Fryns, J.-P., Marynen, P., Froyen, G. <strong>Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination.</strong> Am. J. Hum. Genet. 85: 809-822, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20004760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20004760</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20004760[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.ajhg.2009.10.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20004760">Vandewalle et al. (2009)</a> considered GDI1 the most likely candidate gene in the region, as its copy number correlated perfectly with severity of clinical features and mutations in GDI1 have been found to cause mental retardation. Families 1 and 3 carried 3 copies of GDI1, family 2 carried 5, and family 4, 2. <a href="#5" class="mim-tip-reference" title="Vandewalle, J., Van Esch, H., Govaerts, K., Verbeeck, J., Zweir, C., Madrigal, I., Mila, M., Pijkels, E., Fernandez, I., Kohlase, J., Spaich, C., Rauch, A., Fryns, J.-P., Marynen, P., Froyen, G. <strong>Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination.</strong> Am. J. Hum. Genet. 85: 809-822, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20004760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20004760</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20004760[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.ajhg.2009.10.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20004760">Vandewalle et al. (2009)</a> noted that the duplicated region of chromosome Xq28 harbored by affected individuals did not contain the MECP2 gene (<a href="/entry/300005">300005</a>) and is thus distinct from the duplicated region associated with MECP2 duplication syndrome (<a href="/entry/300260">300260</a>). Clinical features also differ. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20004760" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Fusco, F., D'Urso, M., Miano, M. G., Ursini, M. V. <strong>The LCR at the IKBKG locus is prone to recombine. (Letter)</strong> Am. J. Hum. Genet. 86: 650-652, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20380930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20380930</a>] [<a href="https://doi.org/10.1016/j.ajhg.2009.12.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20380930">Fusco et al. (2010)</a> commented on the paper by <a href="#5" class="mim-tip-reference" title="Vandewalle, J., Van Esch, H., Govaerts, K., Verbeeck, J., Zweir, C., Madrigal, I., Mila, M., Pijkels, E., Fernandez, I., Kohlase, J., Spaich, C., Rauch, A., Fryns, J.-P., Marynen, P., Froyen, G. <strong>Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination.</strong> Am. J. Hum. Genet. 85: 809-822, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20004760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20004760</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20004760[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.ajhg.2009.10.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20004760">Vandewalle et al. (2009)</a>. They differed with the conclusion of <a href="#5" class="mim-tip-reference" title="Vandewalle, J., Van Esch, H., Govaerts, K., Verbeeck, J., Zweir, C., Madrigal, I., Mila, M., Pijkels, E., Fernandez, I., Kohlase, J., Spaich, C., Rauch, A., Fryns, J.-P., Marynen, P., Froyen, G. <strong>Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination.</strong> Am. J. Hum. Genet. 85: 809-822, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20004760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20004760</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20004760[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.ajhg.2009.10.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20004760">Vandewalle et al. (2009)</a> that increased GDI1 expression is likely to be responsible for the mental retardation seen in this duplication syndrome, and considered the IKBKG gene (<a href="/entry/300248">300248</a>), also in the interval, to be likely to play a role in the mental retardation associated with this duplication. <a href="#3" class="mim-tip-reference" title="Fusco, F., D'Urso, M., Miano, M. G., Ursini, M. V. <strong>The LCR at the IKBKG locus is prone to recombine. (Letter)</strong> Am. J. Hum. Genet. 86: 650-652, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20380930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20380930</a>] [<a href="https://doi.org/10.1016/j.ajhg.2009.12.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20380930">Fusco et al. (2010)</a> concluded that the presence of high repetitive DNA sequence families, low copy repeats (LCRs), and a nonprocessed pseudogene sequence in the Xq28 region can enhance homologous recombination, and that several studies had pointed out the ability of L1 and L2 copies to recombine giving rise to both pathologic and nonpathologic structural variants. The recombinant alleles reported by <a href="#5" class="mim-tip-reference" title="Vandewalle, J., Van Esch, H., Govaerts, K., Verbeeck, J., Zweir, C., Madrigal, I., Mila, M., Pijkels, E., Fernandez, I., Kohlase, J., Spaich, C., Rauch, A., Fryns, J.-P., Marynen, P., Froyen, G. <strong>Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination.</strong> Am. J. Hum. Genet. 85: 809-822, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20004760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20004760</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20004760[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.ajhg.2009.10.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20004760">Vandewalle et al. (2009)</a> fit very well with these previous findings. In addition, <a href="#3" class="mim-tip-reference" title="Fusco, F., D'Urso, M., Miano, M. G., Ursini, M. V. <strong>The LCR at the IKBKG locus is prone to recombine. (Letter)</strong> Am. J. Hum. Genet. 86: 650-652, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20380930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20380930</a>] [<a href="https://doi.org/10.1016/j.ajhg.2009.12.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20380930">Fusco et al. (2010)</a> wondered whether any other gene in the duplicated region may play a role in the mental retardation phenotype described by the authors and, in particular, favored the analysis of IKBKG because it is located exactly in the recombination region, and because studies had suggested that any upregulation or decreased expression may cause cellular dysfunction, and thus disease, in a tissue (brain)-specific manner. <a href="#2" class="mim-tip-reference" title="Froyen, G. <strong>Response to Fusco et al. (Letter)</strong> Am. J. Hum. Genet. 86: 652-653, 2010."None>Froyen (2010)</a> replied to <a href="#3" class="mim-tip-reference" title="Fusco, F., D'Urso, M., Miano, M. G., Ursini, M. V. <strong>The LCR at the IKBKG locus is prone to recombine. (Letter)</strong> Am. J. Hum. Genet. 86: 650-652, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20380930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20380930</a>] [<a href="https://doi.org/10.1016/j.ajhg.2009.12.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20380930">Fusco et al. (2010)</a> on behalf of <a href="#5" class="mim-tip-reference" title="Vandewalle, J., Van Esch, H., Govaerts, K., Verbeeck, J., Zweir, C., Madrigal, I., Mila, M., Pijkels, E., Fernandez, I., Kohlase, J., Spaich, C., Rauch, A., Fryns, J.-P., Marynen, P., Froyen, G. <strong>Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination.</strong> Am. J. Hum. Genet. 85: 809-822, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20004760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20004760</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20004760[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.ajhg.2009.10.019" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20004760">Vandewalle et al. (2009)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20380930+20004760" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="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="El-Hattab2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
El-Hattab, A. W., Fang, P., Jin, W., Hughes, J. R., Gibson, J. B., Patel, G. S., Grange, D. K., Manwaring, L. P., Patel, A., Stankiewicz, P., Cheung, S. W.
|
|
<strong>Int22h-1/int22h-2-mediated Xq28 rearrangements: intellectual disability associated with duplications and in utero male lethality with deletions.</strong>
|
|
J. Med. Genet. 48: 840-850, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21984752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21984752</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21984752" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmedgenet-2011-100125" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Froyen2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Froyen, G.
|
|
<strong>Response to Fusco et al. (Letter)</strong>
|
|
Am. J. Hum. Genet. 86: 652-653, 2010.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Fusco2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fusco, F., D'Urso, M., Miano, M. G., Ursini, M. V.
|
|
<strong>The LCR at the IKBKG locus is prone to recombine. (Letter)</strong>
|
|
Am. J. Hum. Genet. 86: 650-652, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20380930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20380930</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20380930" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ajhg.2009.12.019" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Madrigal2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Madrigal, I., Rodriguez-Revenga, L., Armengol, L., Gonzalez, E., Rodriguez, B., Badenas, C., Sanchez, A., Martinez, F., Guitart, M., Fernandez-Carvajal, I., Arranz, J. A., Tejada, M. I., Perez-Jurado, L. A., Estivill, X., Mila, M.
|
|
<strong>X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation.</strong>
|
|
BMC Genomics 8: 443, 2007. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18047645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18047645</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18047645" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1186/1471-2164-8-443" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Vandewalle2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vandewalle, J., Van Esch, H., Govaerts, K., Verbeeck, J., Zweir, C., Madrigal, I., Mila, M., Pijkels, E., Fernandez, I., Kohlase, J., Spaich, C., Rauch, A., Fryns, J.-P., Marynen, P., Froyen, G.
|
|
<strong>Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination.</strong>
|
|
Am. J. Hum. Genet. 85: 809-822, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20004760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20004760</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20004760[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=20004760" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ajhg.2009.10.019" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Vanmarsenille2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vanmarsenille, L., Giannandrea, M., Fieremans, N., Verbeeck, J., Belet, S., Raynaud, M., Vogels, A., Mannik, K., Ounap, K., Jacqueline, V., Briault, S., Van Esch, H., D'Adamo, P., Froyen, G.
|
|
<strong>Increased dosage of RAB39B affects neuronal development and could explain the cognitive impairment in male patients with distal Xq28 copy number gains.</strong>
|
|
Hum. Mutat. 35: 377-383, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24357492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24357492</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24357492" 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.22497" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 3/12/2014
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh - updated : 6/14/2010
|
|
</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">
|
|
Ada Hamosh : 3/18/2010
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 01/19/2016
|
|
</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 : 1/30/2015<br>alopez : 3/20/2014<br>mcolton : 3/18/2014<br>ckniffin : 3/12/2014<br>alopez : 9/7/2012<br>alopez : 10/27/2011<br>terry : 8/10/2011<br>carol : 8/1/2011<br>terry : 9/16/2010<br>alopez : 6/18/2010<br>alopez : 6/17/2010<br>terry : 6/14/2010<br>terry : 4/1/2010<br>alopez : 3/18/2010
|
|
</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> 300815
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
CHROMOSOME Xq28 DUPLICATION SYNDROME
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 1762, 293939;
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: Xq28
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : X:148,000,001-156,040,895 </span>
|
|
</em>
|
|
</strong>
|
|
|
|
</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="1">
|
|
<span class="mim-font">
|
|
Xq28
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Chromosome Xq28 duplication syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
300815
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
4
|
|
</span>
|
|
</td>
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because this disorder is caused by copy number increase of a small region on distal chromosome Xq28. One report has identified a 0.3-Mb region of Xq28 (chrX:153.2-153.5 Mb, NCBI36) containing at least 11 genes and including the GDI1 gene (300104), which is mutated in MRX41 (300849). Two additional reports have identified a more distal 0.5-Mb region (chrX:153.7-154.2 Mb (NCBI36/hg19)) containing at least 8 genes and including the RAB39B gene (300774), which is mutated in MRX72 (300271).</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Vandewalle et al. (2009) reported 4 families with X-linked mental retardation. The first family was of Belgian origin and had 4 affected males in 2 generations. All had normal growth, moderate mental retardation, and variable mild dysmorphic features, including mild 2-3 toe syndactyly, ataxic gait, and strabismus. The second family was of German origin and consisted of 2 affected brothers. The older brother was of average gestational size but was very floppy and was found to have a classic Dandy-Walker malformation, with cerebellar hypoplasia and agenesis of the corpus callosum. He developed seizures at 15 months of age and was microcephalic. Dysmorphic features included large ears, upslanting palpebral fissures, epicanthal folds, and thin lips. His brother also had a Dandy-Walker malformation, with agenesis of the cerebellar vermis and hypoplasia of the corpus callosum. At 19 months he had not developed seizures but had microcephaly. The third family reported by Vandewalle et al. (2009) was of Spanish origin and was reported as case 6 by Madrigal et al. (2007). The index case was born to nonconsanguineous parents at 8 months of pregnancy complicated by an acute pancreatitis. He developed neonatal seizures and cyanotic crises, and was hospitalized for 10 days. Imaging of his brain showed ventricular dilatation and large asymmetric cisterna magna. Gross motor milestones were within normal range. His speech development was delayed. At age 7, he had mild dysmorphic features with microcephaly, a high palate, medial eyebrow flare, and prominent ears. His IQ was 58. Neurologic examination was normal. No clinical details were available for 2 maternal brothers who were institutionalized. The fourth family was a sporadic case born to healthy, unrelated German parents. He had mild global psychomotor delay and did not begin walking until 20 months of age. Mild dysmorphic features were present, including brachycephaly, broad forehead, hypotelorism, and epicanthus inversus, more pronounced at the left side. He had a rather flat midface with flat nasal root and a short philtrum. He had a high palate and a small chin. Head circumference was at the 25th percentile. </p><p>In addition to mental retardation and dysmorphic features, Vandewalle et al. (2009) found ventricular aberrations in 2 families. A large fourth ventricle was seen in family 1, and a ventricular dilatation in family 3. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cytogenetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>El-Hattab et al. (2011) reported 4 boys, including 2 brothers, with intellectual disability and behavioral disorders associated with a recurrent approximately 0.5-Mb duplication of chromosome Xq28 identified through array CGH. The duplications spanned chrX:153.7-154.2 Mb (NCBI36/hg19), and were confirmed by FISH analysis. All 3 mothers, who were more mildly affected with learning difficulties, also carried the duplication. X-chromosome inactivation studies showed skewed patterns in all 3 of the mothers, 2 with preferential inactivation of the normal chromosome and 1 with preferential inactivation of the duplicated chromosome. DNA sequence analysis showed that the breakpoints occurred within the directly oriented low-copy repeat (LCR) regions int22h-1 and int22h-2, which are in or close to the F8 gene (300841). The duplicated region contained 9 genes, including RAB39B (300774), but not GDI1 (300104). All 4 boys with the duplication had cognitive impairment, aggressive and/or hyperactive behavior, recurrent ear infections or pneumonia, and mildly dysmorphic facial features, including high forehead, upper eyelid fullness, broad nasal bridge, and thick lower lip. A mother and daughter from a fourth family were found to carry a heterozygous reciprocal deletion of Xq28 with 100% skewed X-chromosome inactivation of the chromosome with the deletion. Neither had intellectual disability, but the daughter came to attention for hyperactivity, inattentiveness, and sensory integration difficulties. The mother had a history of 2 spontaneous abortions, which El-Hattab et al. (2011) postulated may indicate that the deletion is lethal to males in utero. </p><p>Vanmarsenille et al. (2014) reported 4 male patients, including 2 brothers, with intellectual disability associated with a recurrent approximately 0.5-Mb duplication at distal chromosome Xq28 (chrX: 154.1-154.6 (hg19)). The duplications were apparently the same as those reported by El-Hattab et al. (2011), and the breakpoints involved the int22h-1 and int22h-2 LCRs. The duplicated region was distal to and did not include the GDI1 gene. Cell lines from 2 of the patients showed increased mRNA expression of BRCC3 (300617), VBP1 (300133), and RAB39B. The patients had behavioral or psychiatric problems, including schizophrenia in 1, and variable dysmorphic features, such as high forehead, large ears, deep-set eyes, and thin upper lip. Vanmarsenille et al. (2014) noted that point mutations in the RAB39B gene can cause X-linked mental retardation-72 (MRX72; 300271). Overexpression of Rab39b in mouse primary hippocampal neurons resulted in a significant decrease in neuronal branching as well as a decrease in the number of synapses compared to controls. These findings led Vanmarsenille et al. (2014) to conclude that increased dosage of the RAB39B gene causes disturbed neuronal development leading to cognitive impairment. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In 4 families with X-linked mental retardation, Vandewalle et al. (2009) identified copy number gain of an identical 0.3-Mb region at chromosome Xq28 that included 18 annotated genes. Of these, RPL10 (312173), ATP6AP1 (300197), and GDI1 (300104) are expressed in brain. Vandewalle et al. (2009) considered GDI1 the most likely candidate gene in the region, as its copy number correlated perfectly with severity of clinical features and mutations in GDI1 have been found to cause mental retardation. Families 1 and 3 carried 3 copies of GDI1, family 2 carried 5, and family 4, 2. Vandewalle et al. (2009) noted that the duplicated region of chromosome Xq28 harbored by affected individuals did not contain the MECP2 gene (300005) and is thus distinct from the duplicated region associated with MECP2 duplication syndrome (300260). Clinical features also differ. </p><p>Fusco et al. (2010) commented on the paper by Vandewalle et al. (2009). They differed with the conclusion of Vandewalle et al. (2009) that increased GDI1 expression is likely to be responsible for the mental retardation seen in this duplication syndrome, and considered the IKBKG gene (300248), also in the interval, to be likely to play a role in the mental retardation associated with this duplication. Fusco et al. (2010) concluded that the presence of high repetitive DNA sequence families, low copy repeats (LCRs), and a nonprocessed pseudogene sequence in the Xq28 region can enhance homologous recombination, and that several studies had pointed out the ability of L1 and L2 copies to recombine giving rise to both pathologic and nonpathologic structural variants. The recombinant alleles reported by Vandewalle et al. (2009) fit very well with these previous findings. In addition, Fusco et al. (2010) wondered whether any other gene in the duplicated region may play a role in the mental retardation phenotype described by the authors and, in particular, favored the analysis of IKBKG because it is located exactly in the recombination region, and because studies had suggested that any upregulation or decreased expression may cause cellular dysfunction, and thus disease, in a tissue (brain)-specific manner. Froyen (2010) replied to Fusco et al. (2010) on behalf of Vandewalle et al. (2009). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
El-Hattab, A. W., Fang, P., Jin, W., Hughes, J. R., Gibson, J. B., Patel, G. S., Grange, D. K., Manwaring, L. P., Patel, A., Stankiewicz, P., Cheung, S. W.
|
|
<strong>Int22h-1/int22h-2-mediated Xq28 rearrangements: intellectual disability associated with duplications and in utero male lethality with deletions.</strong>
|
|
J. Med. Genet. 48: 840-850, 2011.
|
|
|
|
|
|
[PubMed: 21984752]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmedgenet-2011-100125]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Froyen, G.
|
|
<strong>Response to Fusco et al. (Letter)</strong>
|
|
Am. J. Hum. Genet. 86: 652-653, 2010.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fusco, F., D'Urso, M., Miano, M. G., Ursini, M. V.
|
|
<strong>The LCR at the IKBKG locus is prone to recombine. (Letter)</strong>
|
|
Am. J. Hum. Genet. 86: 650-652, 2010.
|
|
|
|
|
|
[PubMed: 20380930]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2009.12.019]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Madrigal, I., Rodriguez-Revenga, L., Armengol, L., Gonzalez, E., Rodriguez, B., Badenas, C., Sanchez, A., Martinez, F., Guitart, M., Fernandez-Carvajal, I., Arranz, J. A., Tejada, M. I., Perez-Jurado, L. A., Estivill, X., Mila, M.
|
|
<strong>X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation.</strong>
|
|
BMC Genomics 8: 443, 2007. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 18047645]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1186/1471-2164-8-443]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vandewalle, J., Van Esch, H., Govaerts, K., Verbeeck, J., Zweir, C., Madrigal, I., Mila, M., Pijkels, E., Fernandez, I., Kohlase, J., Spaich, C., Rauch, A., Fryns, J.-P., Marynen, P., Froyen, G.
|
|
<strong>Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination.</strong>
|
|
Am. J. Hum. Genet. 85: 809-822, 2009.
|
|
|
|
|
|
[PubMed: 20004760]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2009.10.019]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vanmarsenille, L., Giannandrea, M., Fieremans, N., Verbeeck, J., Belet, S., Raynaud, M., Vogels, A., Mannik, K., Ounap, K., Jacqueline, V., Briault, S., Van Esch, H., D'Adamo, P., Froyen, G.
|
|
<strong>Increased dosage of RAB39B affects neuronal development and could explain the cognitive impairment in male patients with distal Xq28 copy number gains.</strong>
|
|
Hum. Mutat. 35: 377-383, 2014.
|
|
|
|
|
|
[PubMed: 24357492]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.22497]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 3/12/2014<br>Ada Hamosh - updated : 6/14/2010
|
|
</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">
|
|
Ada Hamosh : 3/18/2010
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 01/19/2016<br>alopez : 1/30/2015<br>alopez : 3/20/2014<br>mcolton : 3/18/2014<br>ckniffin : 3/12/2014<br>alopez : 9/7/2012<br>alopez : 10/27/2011<br>terry : 8/10/2011<br>carol : 8/1/2011<br>terry : 9/16/2010<br>alopez : 6/18/2010<br>alopez : 6/17/2010<br>terry : 6/14/2010<br>terry : 4/1/2010<br>alopez : 3/18/2010
|
|
</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>
|
|
|
|
|