5006 lines
433 KiB
Text
5006 lines
433 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
|
|
|
|
- *602575 - LIM HOMEOBOX TRANSCRIPTION FACTOR 1, BETA; LMX1B
|
|
|
|
|
|
- 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=602575"><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">*602575</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="#geneFunction">Gene Function</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="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/602575">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=ENSG00000136944;t=ENST00000373474" 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=4010" 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=602575" 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=ENSG00000136944;t=ENST00000373474" 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_001174146,NM_001174147,NM_002316" 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_001174147" 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=602575" 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=03986&isoform_id=03986_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/LMX1B" 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/3046880,3132909,3335524,47479658,47480835,85567565,109731283,119608047,119608048,219520075,292494911,292494913,292494915,485956425,957949698,957949701" 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/O60663" 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=4010" 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=ENSG00000136944;t=ENST00000373474" 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=LMX1B" 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=LMX1B" 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+4010" 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/LMX1B" 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:4010" 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/4010" 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=chr9&hgg_gene=ENST00000373474.9&hgg_start=126613928&hgg_end=126701032&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:6654" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:6654" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/gene/lmx1b" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=602575[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=602575[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/ENSG00000136944" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ebi.ac.uk/gwas/search?query=LMX1B" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.gwascentral.org/search?q=LMX1B" 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=LMX1B" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=LMX1B&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/PA30417" 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:6654" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://flybase.org/reports/FBgn0036274.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:1100513" 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/LMX1B#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:1100513" 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/4010/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=4010" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00002988;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-050114-2" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://reactome.org/content/query?q=LMX1B&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> 22199006, 236527004<br />
|
|
|
|
|
|
<strong>ICD10CM:</strong> Q87.2<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>
|
|
602575
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
LIM HOMEOBOX TRANSCRIPTION FACTOR 1, BETA; LMX1B
|
|
|
|
</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">
|
|
LMX1.2
|
|
</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=LMX1B" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">LMX1B</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/9/504?start=-3&limit=10&highlight=504">9q33.3</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr9:126613928-126701032&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'})">9:126,613,928-126,701,032</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=256020,161200" 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/9/504?start=-3&limit=10&highlight=504">
|
|
9q33.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Focal segmental glomerulosclerosis 10
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/256020"> 256020 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Nail-patella syndrome
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/161200"> 161200 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/602575" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/602575" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>The LMX1B gene encodes a transcription factor that belongs to the LIM-homeodomain family of proteins. These proteins are vital for the normal development of dorsal limb structures in vertebrates, components of the renal glomerular filtration barrier, and the anterior segment of the eye (summary by <a href="#16" class="mim-tip-reference" title="Isojima, T., Harita, Y., Furuyama, M., Sugawara, N., Ishizuka, K., Horita, S., Kajiho, Y., Miura, K., Igarashi, T., Hattori, M., Kitanaka, S. <strong>LMX1B mutation with residual transcriptional activity as a cause of isolated glomerulopathy.</strong> Nephrol. Dial. Transplant. 29: 81-88, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24042019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24042019</a>] [<a href="https://doi.org/10.1093/ndt/gft359" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24042019">Isojima et al., 2014</a> and <a href="#12" class="mim-tip-reference" title="Hall, G., Lane, B., Chryst-Ladd, M., Wu, G., Lin, J.-J., Qin, X., Hauser, E. R., Gbadegesin, R. <strong>Dysregulation of WTI (-KTS) is associated with the kidney-specific effects of the LMX1B R246Q mutation.</strong> Sci. Rep. 7: 39933, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28059119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28059119</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28059119[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/srep39933" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28059119">Hall et al., 2017</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=28059119+24042019" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>LIM-homeodomain proteins are characterized by the presence of 2 tandem cysteine/histidine-rich, zinc-binding LIM domains. LMX1 (<a href="/entry/600298">600298</a>), a LIM-homeodomain-containing protein expressed selectively in insulin-producing beta cell lines, has been shown to activate insulin gene transcription. <a href="#15" class="mim-tip-reference" title="Iannotti, C. A., Inoue, H., Bernal, E., Aoki, M., Liu, l., Donis-Keller, H., German, M. S., Permutt, M. A. <strong>Identification of a human LMX1 (LMX1.1)-related gene, LMX1.2: tissue-specific expression and linkage mapping on chromosome 9.</strong> Genomics 46: 520-524, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9441763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9441763</a>] [<a href="https://doi.org/10.1006/geno.1997.5075" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9441763">Iannotti et al. (1997)</a> searched a human EST database with hamster LMX1 sequences to isolate the human LMX1 gene for physical mapping and identification of polymorphic markers. They obtained 2 highly homologous sequences, originally identified by exon trapping of human chromosome 9 (<a href="#5" class="mim-tip-reference" title="Church, D. M., Stotler, C. J., Rutter, J. L., Murrell, J. R., Trofatter, J. A., Buckler, A. J. <strong>Isolation of genes from complex sources of mammalian genomic DNA using exon amplification.</strong> Nature Genet. 6: 98-105, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8136842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8136842</a>] [<a href="https://doi.org/10.1038/ng0194-98" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8136842">Church et al., 1994</a>), and showed that the ESTs represented a closely related but distinct gene, designated LMX1.2 or LMX1B. <a href="#15" class="mim-tip-reference" title="Iannotti, C. A., Inoue, H., Bernal, E., Aoki, M., Liu, l., Donis-Keller, H., German, M. S., Permutt, M. A. <strong>Identification of a human LMX1 (LMX1.1)-related gene, LMX1.2: tissue-specific expression and linkage mapping on chromosome 9.</strong> Genomics 46: 520-524, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9441763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9441763</a>] [<a href="https://doi.org/10.1006/geno.1997.5075" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9441763">Iannotti et al. (1997)</a> found that the sequence of a 482-bp RT-PCR product of human LMX1B and that of the corresponding hamster LMX1 were 92% identical at the amino acid level and that the DNA-binding domains were 100% identical at the amino acid level. They used the human chromosome 9 EST to rescreen the hamster pancreatic islet beta cell library and isolated hamster LMX1B. Sequence comparison suggested that human and hamster LMX1B and chicken LMX1 (<a href="#26" class="mim-tip-reference" title="Vogel, A., Rodriguez, C., Warnken, W., Izpisua Belmonte, J. C. <strong>Dorsal cell fate specified by chick Lmx1 during vertebrate limb development.</strong> Nature 378: 716-720, 1995. Note: Erratum: Nature 379: 848 only, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7501017/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7501017</a>] [<a href="https://doi.org/10.1038/378716a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7501017">Vogel et al., 1995</a>) are homologs of the same gene, which is closely related to hamster LMX1. <a href="#15" class="mim-tip-reference" title="Iannotti, C. A., Inoue, H., Bernal, E., Aoki, M., Liu, l., Donis-Keller, H., German, M. S., Permutt, M. A. <strong>Identification of a human LMX1 (LMX1.1)-related gene, LMX1.2: tissue-specific expression and linkage mapping on chromosome 9.</strong> Genomics 46: 520-524, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9441763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9441763</a>] [<a href="https://doi.org/10.1006/geno.1997.5075" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9441763">Iannotti et al. (1997)</a> performed RT-PCR analysis on total RNAs from 11 adult human tissues and found expression of LMX1B in most of the tissues, with highest levels in testis, thyroid, duodenum, skeletal muscle, and pancreatic islets. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8136842+9441763+7501017" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Dreyer, S. D., Zhou, G., Baldini, A., Winterpacht, A., Zabel, B., Cole, W., Johnson, R. L., Lee, B. <strong>Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome.</strong> Nature Genet. 19: 47-50, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590287</a>] [<a href="https://doi.org/10.1038/ng0598-47" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590287">Dreyer et al. (1998)</a> isolated an LMX1B cDNA and stated that the open reading frame encodes 372 amino acids and contains 2 N-terminal zinc-binding LIM domains, 1 homeodomain, and a C-terminal glutamine-rich domain. The mouse and human sequences are 99% identical. Northern blot analysis of RNA from human fetal and adult tissues revealed a major 7.0-kb transcript abundant in fetal and adult kidney. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590287" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Dunston, J. A., Hamlington, J. D., Zaveri, J., Sweeney, E., Sibbring, J., Tran, C., Malbroux, M., O'Neill, J. P., Mountford, R., McIntosh, I. <strong>The human LMX1B gene: transcription unit, promoter, and pathogenic mutations.</strong> Genomics 84: 565-576, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15498463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15498463</a>] [<a href="https://doi.org/10.1016/j.ygeno.2004.06.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15498463">Dunston et al. (2004)</a> identified an upstream start codon in the LMX1B gene that is in-frame with the previously determined open reading frame, extending the protein to 395 or 402 amino acids, depending on exon 7 splice-site selection. Upstream of this start codon are 2 additional short open reading frames. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15498463" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#9" class="mim-tip-reference" title="Dreyer, S. D., Morello, R., German, M. S., Zabel, B., Winterpacht, A., Lunstrum, G. P., Horton, W. A., Oberg, K. C., Lee, B. <strong>LMX1B transactivation and expression in nail-patella syndrome.</strong> Hum. Molec. Genet. 9: 1067-1074, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10767331/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10767331</a>] [<a href="https://doi.org/10.1093/hmg/9.7.1067" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10767331">Dreyer et al. (2000)</a> noted strong expression of Lmx1b in dorsal mesenchymal tissues (precursors of muscle, tendons, joints, and patella) and also in anterior structures of the murine limb by in situ hybridization, mimicking the anterior to posterior gradient of joint and nail dysplasia observed in patients with nail-patella syndrome (NPS; <a href="/entry/161200">161200</a>). Transfection studies showed that both the LIM domain-interacting protein LDB1 (<a href="/entry/603451">603451</a>) and the helix-loop-helix protein E47/shPan1 (<a href="/entry/147141">147141</a>), regulated LMX1B action. While cotransfections of E47/shPan1 with LMX1B resulted in a synergistic effect on reporter activity, LDB1 downregulated LMX1B-mediated transactivation irrespective of E47/shPan1. Mutant LMX1B proteins containing human mutations affecting each of the helices or the N-terminal arm of the homeodomain abolished transactivation, while LIM B domain and truncation mutations retained residual activity. These mutations failed to act in a dominant-negative manner on wildtype LMX1B in mixing studies, thereby further supporting haploinsufficiency as the mechanism underlying NPS pathogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10767331" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Kania, A., Johnson, R. L., Jessell, T. M. <strong>Coordinate roles for LIM homeobox genes in directing the dorsoventral trajectory of motor axons in the vertebrate limb.</strong> Cell 102: 161-173, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10943837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10943837</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)00022-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10943837">Kania et al. (2000)</a> showed that Lim1 (LHX1; <a href="/entry/601999">601999</a>) and Lmx1b control the initial trajectory of motor axons in the developing mammalian limb. The expression of Lim1 by a lateral set of lateral motor column (LMC) neurons ensured that their axons selected a dorsal trajectory in the limb. In a complementary manner, the expression of Lmx1b by dorsal limb mesenchymal cells was shown to control the dorsal and ventral axonal trajectories of medial and lateral LMC neurons. In the absence of these 2 proteins, motor axons appeared to select dorsal and ventral trajectories at random. Thus, LIM homeodomain proteins act within motor neurons and cells that guide motor axons to establish the fidelity of a binary choice in axonal trajectory. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10943837" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Morello, R., Zhou, G., Dreyer, S. D., Harvey, S. J., Ninomiya, Y., Thorner, P. S., Miner, J. H., Cole, W., Winterpacht, A., Zabel, B., Oberg, K. C., Lee, B. <strong>Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome.</strong> Nature Genet. 27: 205-208, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11175791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11175791</a>] [<a href="https://doi.org/10.1038/84853" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11175791">Morello et al. (2001)</a> reported that, in Lmx1b -/- mice, expression of both the alpha-3 and alpha-4 chains of type IV collagen is strongly diminished in glomerular basement membrane, whereas that of alpha-1, alpha-2, and alpha-5 type IV collagen is unchanged. Moreover, LMX1B binds specifically to a putative enhancer sequence in intron 1 of both mouse and human COL4A4 (<a href="/entry/120131">120131</a>) and upregulates reporter constructs containing this enhancer-like sequence. These data indicated that LMX1B directly regulates the coordinated expression of the alpha-3(IV) and alpha-4(IV) collagen required for normal GBM morphogenesis and that its dysregulation in glomerular basement membrane contributes to the renal pathology and nephrosis in nail-patella syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11175791" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Ding, Y.-Q., Marklund, U., Yuan, W., Yin, J., Wegman, L., Ericson, J., Deneris, E., Johnson, R. L., Chen, Z.-F. <strong>Lmx1b is essential for the development of serotonergic neurons.</strong> Nature Neurosci. 6: 933-938, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12897786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12897786</a>] [<a href="https://doi.org/10.1038/nn1104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12897786">Ding et al. (2003)</a> presented evidence suggesting that Lmx1b is required for the development of 5-HT (5-hydroxytryptamine) neurons in the central nervous system in mice, and that Lmx1b acts as a critical mediator downstream of Shh (<a href="/entry/600725">600725</a>) and Nkx2.2 (<a href="/entry/604612">604612</a>) in a signaling cascade to direct specification and/or differentiation of 5-HT neurons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12897786" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Johnson, R. L., Tabin, C. J. <strong>Molecular models for vertebrate limb development.</strong> Cell 90: 979-990, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9323126/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9323126</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80364-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9323126">Johnson and Tabin (1997)</a> reviewed the role of this gene, which they referred to as LMX1, and others in limb development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9323126" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Marini, M., Giacopelli, F., Seri, M., Ravazzolo, R. <strong>Interaction of the LMX1B and PAX2 gene products suggests possible molecular basis of differential phenotypes in nail-patella syndrome.</strong> Europ. J. Hum. Genet. 13: 789-792, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15785774/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15785774</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15785774">Marini et al. (2005)</a> demonstrated an interaction between LMX1B and the PAX2 gene (<a href="/entry/167409">167409</a>) using both direct yeast 2-hybrid assays and coimmunoprecipitation studies. Experiments with deletion constructs indicated that the LMX1B homeodomain interacted with the PAX2 homeodomain. <a href="#21" class="mim-tip-reference" title="Marini, M., Giacopelli, F., Seri, M., Ravazzolo, R. <strong>Interaction of the LMX1B and PAX2 gene products suggests possible molecular basis of differential phenotypes in nail-patella syndrome.</strong> Europ. J. Hum. Genet. 13: 789-792, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15785774/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15785774</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201405" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15785774">Marini et al. (2005)</a> suggested that PAX2 may be a modifier gene in NPS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15785774" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By analyzing Lmx1b conditional knockout mice, <a href="#8" class="mim-tip-reference" title="Donovan, L. J., Spencer, W. C., Kitt, M. M., Eastman, B. A., Lobur, K. J., Jiao, K., Silver, J., Deneris, E. S. <strong>Lmx1b is required at multiple stages to build expansive serotonergic axon architectures.</strong> eLife 8: e48788, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31355748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31355748</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31355748[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/10.7554/eLife.48788" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31355748">Donovan et al. (2019)</a> showed that Lmx1b was required for formation of both ascending and descending 5-HT axon projection pathways, as Lmx1b deficiency in 5-HT neurons resulted in delayed primary pathway formation followed by a profound failure of ascending axons to selectively route into preexisting fiber tracts. Stage-specific knockdown of Lmx1b at different early postnatal timepoints of mouse development revealed that Lmx1b acted temporally at successive stages to control 5-HT axon primary outgrowth, selective routing, and terminal arborization. RNA-sequencing analysis revealed that Lmx1b controlled axon-related transcriptomes and identified an ascending-specific axonal Lmx1b-to-Pet1 (FEV; <a href="/entry/607150">607150</a>) regulatory cascade. Lmx1b acted through Pet1 continually over an extended postnatal period to control stage-specific gene expression and to generate both early and late 5-HT terminal arbor patterns in different forebrain regions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31355748" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="#27" class="mim-tip-reference" title="Vollrath, D., Jaramillo-Babb, V. L., Clough, M. V., McIntosh, I., Scott, K. M., Lichter, P. R., Richards, J. E. <strong>Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome.</strong> Hum. Molec. Genet. 7: 1091-1098, 1998. Erratum: Hum. Molec. Genet. 7: 1333 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9618165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9618165</a>] [<a href="https://doi.org/10.1093/hmg/7.7.1091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9618165">Vollrath et al. (1998)</a> determined that the LMX1B gene contains at least 8 exons in a genomic region with high CG content. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9618165" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Dunston, J. A., Hamlington, J. D., Zaveri, J., Sweeney, E., Sibbring, J., Tran, C., Malbroux, M., O'Neill, J. P., Mountford, R., McIntosh, I. <strong>The human LMX1B gene: transcription unit, promoter, and pathogenic mutations.</strong> Genomics 84: 565-576, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15498463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15498463</a>] [<a href="https://doi.org/10.1016/j.ygeno.2004.06.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15498463">Dunston et al. (2004)</a> determined that the LMX1B transcription start site is located within a cluster of 4 CpG islands and is not associated with a consensus TATA box. The 5-prime UTR contains CCAAT boxes, a basic transcription element, and binding sites for SP1 (<a href="/entry/189906">189906</a>), OCT1 (<a href="/entry/164175">164175</a>), and TCF (<a href="/entry/142410">142410</a>)/LEF1 (<a href="/entry/153245">153245</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15498463" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>By PCR analysis of rodent-human somatic cell hybrid DNA, <a href="#15" class="mim-tip-reference" title="Iannotti, C. A., Inoue, H., Bernal, E., Aoki, M., Liu, l., Donis-Keller, H., German, M. S., Permutt, M. A. <strong>Identification of a human LMX1 (LMX1.1)-related gene, LMX1.2: tissue-specific expression and linkage mapping on chromosome 9.</strong> Genomics 46: 520-524, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9441763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9441763</a>] [<a href="https://doi.org/10.1006/geno.1997.5075" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9441763">Iannotti et al. (1997)</a> confirmed the mapping of the LMX1 gene to chromosome 1 and the LMX1B gene to chromosome 9. The authors identified a simple sequence repeat polymorphisms in a P1 genomic clone containing LMX1B and used the resulting polymorphic markers to construct a genetic linkage map that localized LMX1B to 9q32-q34.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9441763" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Nail-Patella Syndrome</em></strong></p><p>
|
|
<a href="#10" class="mim-tip-reference" title="Dreyer, S. D., Zhou, G., Baldini, A., Winterpacht, A., Zabel, B., Cole, W., Johnson, R. L., Lee, B. <strong>Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome.</strong> Nature Genet. 19: 47-50, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590287</a>] [<a href="https://doi.org/10.1038/ng0598-47" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590287">Dreyer et al. (1998)</a> identified de novo heterozygous mutations in the LMX1B gene (<a href="/entry/161200#0001">161200.0001</a>-<a href="/entry/161200#0003">161200.0003</a>) in 3 unrelated patients with nail-patella syndrome (NPS; <a href="/entry/161200">161200</a>). Functional studies showed that one of these mutations disrupted sequence-specific DNA binding, while the other 2 mutations resulted in premature termination of translation. All 3 patients had presented in early childhood with nail dysplasia involving at least the thumbs, elbow stiffness with limitation of pronation and supination, and poorly ossified, malformed patellae. They also had classic radiographic features, including iliac flaring and iliac horns. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590287" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Vollrath, D., Jaramillo-Babb, V. L., Clough, M. V., McIntosh, I., Scott, K. M., Lichter, P. R., Richards, J. E. <strong>Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome.</strong> Hum. Molec. Genet. 7: 1091-1098, 1998. Erratum: Hum. Molec. Genet. 7: 1333 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9618165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9618165</a>] [<a href="https://doi.org/10.1093/hmg/7.7.1091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9618165">Vollrath et al. (1998)</a> sequenced a large segment of LMX1B from the genomic DNA of probands from 4 families with nail-patella syndrome and open angle glaucoma (OAG; see <a href="/entry/137760">137760</a>) and identified 4 mutations: 2 stop codons, a deletion causing a frameshift, and a missense mutation in a functionally important residue. The presence of these putative loss-of-function mutations in the DNA of individuals with NPS indicated that haploinsufficiency of LMX1B underlies this disorder. The results helped explain the high degree of variability in the NPS phenotype, and suggested that the skeletal defects in NPS are a result of the diminished dorsoventral patterning activity of LMX1B protein during limb development. The results further suggested that the NPS and OAG phenotypes in the families studied resulted from mutations in a single gene, LMX1B. Although renal abnormalities accompanying NPS were well known, the cosegregation of open angle glaucoma with NPS in other families (<a href="#20" class="mim-tip-reference" title="Lichter, P. R., Richards, J. E., Downs, C. A., Stringham, H. M., Boehnke, M., Farley, F. A. <strong>Cosegregation of open-angle glaucoma and the nail-patella syndrome.</strong> Am. J. Ophthal. 124: 506-515, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9323941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9323941</a>] [<a href="https://doi.org/10.1016/s0002-9394(14)70866-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9323941">Lichter et al., 1997</a>) was a less well-known finding. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9618165+9323941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="McIntosh, I., Dreyer, S. D., Clough, M. V., Dunston, J. A., Eyaid, W., Roig, C. M., Montgomery, T., Ala-Mello, S., Kaitila, I., Winterpacht, A., Zabel, B., Frydman, M., Cole, W. G., Francomano, C. A., Lee, B. <strong>Mutation analysis of LMX1B gene in nail-patella syndrome patients.</strong> Am. J. Hum. Genet. 63: 1651-1658, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837817</a>] [<a href="https://doi.org/10.1086/302165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9837817">McIntosh et al. (1998)</a> screened 41 NPS families for LMX1B mutations. A total of 25 mutations were identified in 37 families. The nature of the mutations supported the hypothesis that NPS is the result of haploinsufficiency for LMX1B. There was no evidence of correlation between aspects of the NPS phenotype and specific mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837817" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Clough, M. V., Hamlington, J. D., McIntosh, I. <strong>Restricted distribution of loss-of-function mutations within the LMX1B genes of nail-patella syndrome patients.</strong> Hum. Mutat. 14: 459-465, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10571942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10571942</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(199912)14:6<459::AID-HUMU3>3.0.CO;2-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10571942">Clough et al. (1999)</a> stated that a total of 64 point mutations and small deletions or insertions in the LMX1B gene had been reported and that they were concentrated within either the LIM or homeodomains. No nail-patella syndrome mutations had been observed within the C-terminal third of the coding sequence, suggesting that mutations in this region are not inactivating. These findings supported the hypothesis that NPS results from a 50% reduction in LMX1B function via a reduction in synthesis, disruption of secondary structure, or failure to bind DNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10571942" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Dunston, J. A., Hamlington, J. D., Zaveri, J., Sweeney, E., Sibbring, J., Tran, C., Malbroux, M., O'Neill, J. P., Mountford, R., McIntosh, I. <strong>The human LMX1B gene: transcription unit, promoter, and pathogenic mutations.</strong> Genomics 84: 565-576, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15498463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15498463</a>] [<a href="https://doi.org/10.1016/j.ygeno.2004.06.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15498463">Dunston et al. (2004)</a> identified 47 additional mutations within the coding region of the LMX1B gene, as well as 9 deletions of large portions of the gene. No mutations were identified in the promoter or in highly conserved intronic sequences. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15498463" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 multiplex ligation-probe amplification (MLPA) analysis, <a href="#1" class="mim-tip-reference" title="Bongers, E. M. H. F., de Wijs, I. J., Marcelis, C., Hoefsloot, L. H., Knoers, N. V. A. M. <strong>Identification of entire LMX1B gene deletions in nail patella syndrome: evidence for haploinsufficiency as the main pathogenic mechanism underlying dominant inheritance in man.</strong> Europ. J. Hum. Genet. 16: 1240-1244, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18414507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18414507</a>] [<a href="https://doi.org/10.1038/ejhg.2008.83" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18414507">Bongers et al. (2008)</a> identified a heterozygous deletion of the entire LMX1B gene (<a href="#0013">602575.0013</a>) in 2 unrelated patients with nail-patella syndrome. The phenotype was similar to other reported cases with point or truncating mutations. The findings confirmed that haploinsufficiency of LMX1B is the pathogenic mechanism in nail-patella syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18414507" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Focal Segmental Glomerulosclerosis 10</em></strong></p><p>
|
|
In 5 affected members of a large multigenerational family (family F) with focal segmental glomerulosclerosis-10 (FSGS10; <a href="/entry/256020">256020</a>), <a href="#3" class="mim-tip-reference" title="Boyer, O., Woerner, S., Yang, F., Oakeley, E. J., Linghu, B., Gribouval, O., Tete, M.-J., Duca, J. S., Klickstein, L., Damask, A. J., Szustakowski, J. D., Heibel, F., and 10 others. <strong>LMX1B mutations cause hereditary FSGS without extrarenal involvement.</strong> J. Am. Soc. Nephrol. 24: 1216-1222, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23687361/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23687361</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23687361[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/10.1681/ASN.2013020171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23687361">Boyer et al. (2013)</a> identified a heterozygous missense mutation in the LMX1B gene (R246Q; <a href="#0014">602575.0014</a>). The mutation, which was found by a combination of linkage analysis and exome sequencing, segregated with the disorder in the family. Direct sequencing of the LMX1B gene in a cohort of 73 unrelated families with a similar phenotype identified a heterozygous R246Q mutation in an affected mother and daughter (family V) and a heterozygous R246P (<a href="#0015">602575.0015</a>) mutation in an affected father and daughter (family B). Neither variant was present in the Exome Sequencing Project. Functional studies of the variants and studies of patient cells were not performed, but <a href="#3" class="mim-tip-reference" title="Boyer, O., Woerner, S., Yang, F., Oakeley, E. J., Linghu, B., Gribouval, O., Tete, M.-J., Duca, J. S., Klickstein, L., Damask, A. J., Szustakowski, J. D., Heibel, F., and 10 others. <strong>LMX1B mutations cause hereditary FSGS without extrarenal involvement.</strong> J. Am. Soc. Nephrol. 24: 1216-1222, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23687361/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23687361</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23687361[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/10.1681/ASN.2013020171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23687361">Boyer et al. (2013)</a> noted that residue R246 is highly conserved and located in the homeobox domain, which is important for DNA binding and transcriptional activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23687361" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 6-year-old Japanese girl with FSGS10, <a href="#16" class="mim-tip-reference" title="Isojima, T., Harita, Y., Furuyama, M., Sugawara, N., Ishizuka, K., Horita, S., Kajiho, Y., Miura, K., Igarashi, T., Hattori, M., Kitanaka, S. <strong>LMX1B mutation with residual transcriptional activity as a cause of isolated glomerulopathy.</strong> Nephrol. Dial. Transplant. 29: 81-88, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24042019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24042019</a>] [<a href="https://doi.org/10.1093/ndt/gft359" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24042019">Isojima et al. (2014)</a> identified a de novo heterozygous R246Q substitution in the LMX1B gene. The mutation, which was found by direct sequencing of the LMX1B gene, was not present in the dbSNP database or among Japanese controls. In vitro functional expression studies showed that the mutation partially impaired transcriptional activity of LMX1B compared to controls, but not to the extent as mutations associated with NPS. There was no evidence for a dominant-negative effect, and the authors postulated haploinsufficiency. Renal biopsy from the patient showed podocyte effacement, a thickened glomerular basement membrane (GBM) due to abnormal deposition of type III collagen, and altered expression of CD2AP (<a href="/entry/604241">604241</a>), which plays a role in podocyte development and cytoskeleton remodeling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24042019" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 18 affected members from 2 large multigenerational families (DUK35705 and DUK34319) with FSGS10, <a href="#12" class="mim-tip-reference" title="Hall, G., Lane, B., Chryst-Ladd, M., Wu, G., Lin, J.-J., Qin, X., Hauser, E. R., Gbadegesin, R. <strong>Dysregulation of WTI (-KTS) is associated with the kidney-specific effects of the LMX1B R246Q mutation.</strong> Sci. Rep. 7: 39933, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28059119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28059119</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28059119[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/srep39933" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28059119">Hall et al. (2017)</a> identified a heterozygous R246Q mutation in the LMX1B gene. The mutation, which was found by a combination of linkage analysis and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. In vitro functional expression studies in human podocyte cell lines transfected with the mutation showed altered expression of certain key podocyte genes, suggesting that the mutation may exert a haploinsufficiency effect on the transcriptional regulation of these genes. However, additional studies indicated that the R246Q mutation exerted a dominant-negative effect on certain WT1 (<a href="/entry/607102">607102</a>) isoforms, which may have also caused alterations in the expression of podocyte-related genes. <a href="#12" class="mim-tip-reference" title="Hall, G., Lane, B., Chryst-Ladd, M., Wu, G., Lin, J.-J., Qin, X., Hauser, E. R., Gbadegesin, R. <strong>Dysregulation of WTI (-KTS) is associated with the kidney-specific effects of the LMX1B R246Q mutation.</strong> Sci. Rep. 7: 39933, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28059119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28059119</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28059119[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/srep39933" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28059119">Hall et al. (2017)</a> noted that the renal glomerular phenotype observed in these patients includes a wide variety of light microscopic findings, including focal segmental glomerulosclerosis, minimal change disease, membranous nephropathy, and even immune complex glomerulonephritis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28059119" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 heterozygous R246Q mutation was identified in patients with FSGS10 by <a href="#19" class="mim-tip-reference" title="Lei, L., Oh, G., Sutherland, S., Abra, G., Higgins, J., Sibley, R., Troxell, M., Kambham, N. <strong>Myelin bodies in LMX1B-associated nephropathy: potential for misdiagnosis.</strong> Pediat. Nephrol. 35: 1647-1657, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32356190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32356190</a>] [<a href="https://doi.org/10.1007/s00467-020-04564-w" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32356190">Lei et al. (2020)</a> and <a href="#25" class="mim-tip-reference" title="Pinto e Vairo, F., Pichurin, P. N., Fervenza, F. C., Nasr, S. H., Mills, K., Schmitz, C. T., Klee, E. W., Herrmann, S. M. <strong>Nail-patella-like renal disease masquerading as Fabry disease on kidney biopsy: a case report.</strong> BMC Nephrol. 21: 341, 2020. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32791958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32791958</a>] [<a href="https://doi.org/10.1186/s12882-020-02012-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32791958">Pinto e Vairo et al. (2020)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=32791958+32356190" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="genotypePhenotypeCorrelations" class="mim-anchor"></a>
|
|
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGenotypePhenotypeCorrelationsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#2" class="mim-tip-reference" title="Bongers, E. M. H. F., Huysmans, F. T., Levtchenko, E., de Rooy, J. W., Blickman, J. G., Admiraal, R. J. C., Huygen, P. L. M., Cruysberg, J. R. M., Toolens, P. A. M. P., Prins, J. B., Krabbe, P. F. M., Borm, G. F., Schoots, J., van Bokhoven, H., van Remortele, A. M. F., Hoefsloot, L. H., van Kampen, A., Knoers, N. V. A. M. <strong>Genotype-phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy.</strong> Europ. J. Hum. Genet. 13: 935-946, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15928687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15928687</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201446" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15928687">Bongers et al. (2005)</a> performed LMX1B mutation analysis and comprehensive examinations in 106 subjects from 32 NPS families and found that individuals with an LMXB1 mutation located in the homeodomain showed significantly more frequent and higher values of nephropathy and proteinuria than subjects with mutations in the LIM domains. No clear genotype-phenotype association was apparent for extrarenal manifestations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15928687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>Dorsoventral limb patterning in vertebrates is controlled by the LIM-homeodomain protein Lmx1b, which is expressed in a spatially and temporally restricted manner along the dorsoventral limb axis (<a href="#26" class="mim-tip-reference" title="Vogel, A., Rodriguez, C., Warnken, W., Izpisua Belmonte, J. C. <strong>Dorsal cell fate specified by chick Lmx1 during vertebrate limb development.</strong> Nature 378: 716-720, 1995. Note: Erratum: Nature 379: 848 only, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7501017/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7501017</a>] [<a href="https://doi.org/10.1038/378716a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7501017">Vogel et al., 1995</a>). <a href="#4" class="mim-tip-reference" title="Chen, H., Lun, Y., Ovchinnikov, D., Kokubo, H., Oberg, K. C., Pepicelli, C. V., Gan, L., Lee, B., Johnson, R. L. <strong>Limb and kidney defects in Lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome.</strong> Nature Genet. 19: 51-55, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590288</a>] [<a href="https://doi.org/10.1038/ng0598-51" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590288">Chen et al. (1998)</a> described a phenotype resulting from targeted disruption of Lmx1b in mice. The results demonstrated that Lmx1b is essential for the specification of dorsal limb fate at both the zeugopodal and autopodal levels with prominent phenotypes including absence of nails and patellae. Using an interspecific backcross panel, <a href="#24" class="mim-tip-reference" title="Pilz, A., Prohaska, R., Peters, J., Abbott, C. <strong>Genetic linkage analysis of the Ak1, Col5a1, Epb7.2, Fpgs, Grp78, Pbx3, and Notch1 genes in the region of mouse chromosome 2 homologous to human chromosome 9q.</strong> Genomics 21: 104-109, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8088777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8088777</a>] [<a href="https://doi.org/10.1006/geno.1994.1230" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8088777">Pilz et al. (1994)</a> mapped the Lmx1b gene to the distal portion of mouse chromosome 2 in a region syntenic to human 9q34, where the nail-patella syndrome gene is located. Furthermore, kidneys of Lmx1b mutant mice exhibited pathologic changes similar to those observed in nail-patella syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8088777+7501017+9590288" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Hamano, Y., Grunkemeyer, J. A., Sudhakar, A., Zeisberg, M., Cosgrove, D., Morello, R., Lee, B., Sugimoto, H., Kalluri, R. <strong>Determinants of vascular permeability in the kidney glomerulus.</strong> J. Biol. Chem. 277: 31154-31162, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12039968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12039968</a>] [<a href="https://doi.org/10.1074/jbc.M204806200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12039968">Hamano et al. (2002)</a> characterized the renal defects of mice deficient in Lmx1b, which controls the expression of several glomerulus-specific proteins. Lmx1b-null mice died immediately after birth with massive glomerular vascular leaks. Glomerular basement membranes of these mice showed altered architecture, reduced expression of the type IV collagens alpha-3 (<a href="/entry/120070">120070</a>) and alpha-4 (COL4A4), and altered expression of the slit diaphragm proteins nephrin (<a href="/entry/602716">602716</a>) and podocin (<a href="/entry/604766">604766</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12039968" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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>15 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/602575" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=602575[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 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMX1B, ASN269LYS
|
|
</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> rs121909486 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909486;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/rs121909486?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=rs121909486" 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=rs121909486" 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=RCV000007415 OR RCV001380261 OR RCV005049319" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007415, RCV001380261, RCV005049319" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007415...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with nail-patella syndrome (NPS; <a href="/entry/161200">161200</a>) who presented at 5 years of age with elbow contractures without evidence of ocular or renal abnormalities, <a href="#10" class="mim-tip-reference" title="Dreyer, S. D., Zhou, G., Baldini, A., Winterpacht, A., Zabel, B., Cole, W., Johnson, R. L., Lee, B. <strong>Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome.</strong> Nature Genet. 19: 47-50, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590287</a>] [<a href="https://doi.org/10.1038/ng0598-47" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590287">Dreyer et al. (1998)</a> found a C-to-A transversion in the LMX1B gene that resulted in substitution of lysine for asparagine at amino acid position 246. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590287" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Dunston, J. A., Hamlington, J. D., Zaveri, J., Sweeney, E., Sibbring, J., Tran, C., Malbroux, M., O'Neill, J. P., Mountford, R., McIntosh, I. <strong>The human LMX1B gene: transcription unit, promoter, and pathogenic mutations.</strong> Genomics 84: 565-576, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15498463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15498463</a>] [<a href="https://doi.org/10.1016/j.ygeno.2004.06.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15498463">Dunston et al. (2004)</a> identified an upstream start codon in-frame with the published open reading frame of the LMX1B gene, revealing an additional 23 amino acids in-frame with the reported start codon; thus, this mutation results in an asn269-to-lys (N269K) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15498463" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMX1B, ARG221TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121909487 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909487;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=rs121909487" 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=rs121909487" 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=RCV000007416 OR RCV001388091" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007416, RCV001388091" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007416...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with typical nail-patella syndrome (NPS; <a href="/entry/161200">161200</a>), who presented at 6 years with joint stiffness and irregular pigmentation of the iris, but without evidence of kidney dysfunction, <a href="#10" class="mim-tip-reference" title="Dreyer, S. D., Zhou, G., Baldini, A., Winterpacht, A., Zabel, B., Cole, W., Johnson, R. L., Lee, B. <strong>Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome.</strong> Nature Genet. 19: 47-50, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590287</a>] [<a href="https://doi.org/10.1038/ng0598-47" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590287">Dreyer et al. (1998)</a> found a C-to-T transition in the LMX1B gene that resulted in an arg198-to-ter substitution was predicted to cause premature termination of the polypeptide with abolition of both the homeodomain and the putative glutamine-rich activation domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590287" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Dunston, J. A., Hamlington, J. D., Zaveri, J., Sweeney, E., Sibbring, J., Tran, C., Malbroux, M., O'Neill, J. P., Mountford, R., McIntosh, I. <strong>The human LMX1B gene: transcription unit, promoter, and pathogenic mutations.</strong> Genomics 84: 565-576, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15498463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15498463</a>] [<a href="https://doi.org/10.1016/j.ygeno.2004.06.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15498463">Dunston et al. (2004)</a> identified an upstream start codon in-frame with the published open reading frame of the LMX1B gene, revealing an additional 23 amino acids in-frame with the reported start codon; thus, this mutation results in an arg221-to-ter (R221X) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15498463" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMX1B, 1-BP INS, 713A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007417" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007417" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007417</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with classic features of nail-patella syndrome (NPS; <a href="/entry/161200">161200</a>) who presented in infancy with proteinuria and ultimately developed nephrotic syndrome, <a href="#10" class="mim-tip-reference" title="Dreyer, S. D., Zhou, G., Baldini, A., Winterpacht, A., Zabel, B., Cole, W., Johnson, R. L., Lee, B. <strong>Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome.</strong> Nature Genet. 19: 47-50, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590287</a>] [<a href="https://doi.org/10.1038/ng0598-47" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9590287">Dreyer et al. (1998)</a> identified a single nucleotide A insertion in the LMX1B gene, resulting in a frameshift mutation disrupting the reading frame at codon 233 in the homeodomain and predicting translation termination at codon 327 in the glutamine-rich C-terminal domain (713insA). Light microscopic analysis of a kidney biopsy from this patient showed only mild interstitial fibrosis; ultrastructural studies revealed thickened and split glomerular basement membranes, and fusion and hyperplasia of foot processes similar to that identified in Lmx1b -/- mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590287" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMX1B, CYS95PHE
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121909488 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909488;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=rs121909488" 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=rs121909488" 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=RCV000007418" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007418" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007418</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-generation family (UM:47) of German ancestry, <a href="#27" class="mim-tip-reference" title="Vollrath, D., Jaramillo-Babb, V. L., Clough, M. V., McIntosh, I., Scott, K. M., Lichter, P. R., Richards, J. E. <strong>Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome.</strong> Hum. Molec. Genet. 7: 1091-1098, 1998. Erratum: Hum. Molec. Genet. 7: 1333 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9618165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9618165</a>] [<a href="https://doi.org/10.1093/hmg/7.7.1091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9618165">Vollrath et al. (1998)</a> found typical features of nail-patella syndrome (NPS; <a href="/entry/161200">161200</a>) in all members who had open angle glaucoma, as well as in members who did not have POAG. Proteinuria was not present. Age at onset of glaucoma ranged from 18 to 41 years (mean, 32 years). The proband was found to be heterozygous for a G-to-T transversion in exon 3 of the LMX1B gene that resulted in a cys95-to-phe amino acid substitution in the LIM2 domain of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9618165" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMX1B, 2-BP DEL, 233TG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007419 OR RCV002512873" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007419, RCV002512873" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007419...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-generation family (UM:65) of French and Irish ancestry, <a href="#27" class="mim-tip-reference" title="Vollrath, D., Jaramillo-Babb, V. L., Clough, M. V., McIntosh, I., Scott, K. M., Lichter, P. R., Richards, J. E. <strong>Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome.</strong> Hum. Molec. Genet. 7: 1091-1098, 1998. Erratum: Hum. Molec. Genet. 7: 1333 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9618165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9618165</a>] [<a href="https://doi.org/10.1093/hmg/7.7.1091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9618165">Vollrath et al. (1998)</a> found that the proband and 6 other individuals with glaucoma also had nail-patella syndrome (NPS; <a href="/entry/161200">161200</a>). Age at onset of glaucoma ranged from birth to 54 years (mean, 24 years). Proteinuria was not found in family members who were screened, but medical records indicated that the proband's mother had proteinuria and kidney disease. The proband of family UM:65 was heterozygous for a 2-bp deletion in exon 2 (233delTG) of the LMX1B gene, predicting a severely truncated protein that lacks part of the LIM1 domain and all of the LIM2 and homeodomains, and contains a stretch of 44 N-terminal amino acid residues generated from an incorrect reading frame. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9618165" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMX1B, GLN59TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121909489 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909489;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=rs121909489" 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=rs121909489" 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=RCV000007420 OR RCV000760427 OR RCV005049320" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007420, RCV000760427, RCV005049320" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007420...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#27" class="mim-tip-reference" title="Vollrath, D., Jaramillo-Babb, V. L., Clough, M. V., McIntosh, I., Scott, K. M., Lichter, P. R., Richards, J. E. <strong>Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome.</strong> Hum. Molec. Genet. 7: 1091-1098, 1998. Erratum: Hum. Molec. Genet. 7: 1333 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9618165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9618165</a>] [<a href="https://doi.org/10.1093/hmg/7.7.1091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9618165">Vollrath et al. (1998)</a> reported that members of family UM:68 with nail-patella syndrome (NPS; <a href="/entry/161200">161200</a>) and open angle glaucoma had features of NPS that were said to have come from a Cherokee Indian ancestor. Age at onset of OAG ranged from 40 to 77 years (mean, approximately 56 years). In contrast to the other 3 families studied by <a href="#27" class="mim-tip-reference" title="Vollrath, D., Jaramillo-Babb, V. L., Clough, M. V., McIntosh, I., Scott, K. M., Lichter, P. R., Richards, J. E. <strong>Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome.</strong> Hum. Molec. Genet. 7: 1091-1098, 1998. Erratum: Hum. Molec. Genet. 7: 1333 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9618165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9618165</a>] [<a href="https://doi.org/10.1093/hmg/7.7.1091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9618165">Vollrath et al. (1998)</a>, all of the individuals with NPS in UM:68 were reported to have proteinuria. The proband of UM:68 was heterozygous for a C-to-T transition in exon 2 of the LMX1B gene that created a premature stop codon (gln59 to ter). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9618165" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMX1B, ARG208TER
|
|
</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> rs121909490 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909490;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/rs121909490?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=rs121909490" 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=rs121909490" 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=RCV000007421 OR RCV000414681 OR RCV004639120" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007421, RCV000414681, RCV004639120" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007421...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#27" class="mim-tip-reference" title="Vollrath, D., Jaramillo-Babb, V. L., Clough, M. V., McIntosh, I., Scott, K. M., Lichter, P. R., Richards, J. E. <strong>Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome.</strong> Hum. Molec. Genet. 7: 1091-1098, 1998. Erratum: Hum. Molec. Genet. 7: 1333 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9618165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9618165</a>] [<a href="https://doi.org/10.1093/hmg/7.7.1091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9618165">Vollrath et al. (1998)</a> described an LMX1B mutation, arg208 to ter, as the cause of nail-patella syndrome (NPS; <a href="/entry/161200">161200</a>) and open angle glaucoma in a Caucasian family (UM:310). No proteinuria was known in the family. As in the other families studied by <a href="#27" class="mim-tip-reference" title="Vollrath, D., Jaramillo-Babb, V. L., Clough, M. V., McIntosh, I., Scott, K. M., Lichter, P. R., Richards, J. E. <strong>Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome.</strong> Hum. Molec. Genet. 7: 1091-1098, 1998. Erratum: Hum. Molec. Genet. 7: 1333 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9618165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9618165</a>] [<a href="https://doi.org/10.1093/hmg/7.7.1091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9618165">Vollrath et al. (1998)</a>, the severity of fingernail anomalies ranged from mild ridging to hypoplasia and aplasia. Elbow mobility was likewise variable. Age at onset of glaucoma ranged from 40 to 50 years (mean, 45 years). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9618165" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMX1B, ARG200GLN
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121909491 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909491;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=rs121909491" 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=rs121909491" 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=RCV000007422 OR RCV001388092 OR RCV004748508 OR RCV005042000" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007422, RCV001388092, RCV004748508, RCV005042000" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007422...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#22" class="mim-tip-reference" title="McIntosh, I., Dreyer, S. D., Clough, M. V., Dunston, J. A., Eyaid, W., Roig, C. M., Montgomery, T., Ala-Mello, S., Kaitila, I., Winterpacht, A., Zabel, B., Frydman, M., Cole, W. G., Francomano, C. A., Lee, B. <strong>Mutation analysis of LMX1B gene in nail-patella syndrome patients.</strong> Am. J. Hum. Genet. 63: 1651-1658, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837817</a>] [<a href="https://doi.org/10.1086/302165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9837817">McIntosh et al. (1998)</a> described a 599G-A transition in the LM1B gene, resulting in an arg200-to-gln amino acid substitution in the homeodomain, in 5 presumably unrelated families with nail-patella syndrome (NPS; <a href="/entry/161200">161200</a>). The mutation ablated a MspI restriction site. Putatively the gene had an effect on DNA binding. The recurrence of this mutation was not unexpected, since it was the result of a transition at a CpG dinucleotide. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837817" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMX1B, 672, G-A, +1
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1427331961 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1427331961;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/rs1427331961?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=rs1427331961" 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=rs1427331961" 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=RCV000007423" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007423" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007423</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family in which 3 members had nail-patella syndrome (NPS; <a href="/entry/161200">161200</a>), <a href="#22" class="mim-tip-reference" title="McIntosh, I., Dreyer, S. D., Clough, M. V., Dunston, J. A., Eyaid, W., Roig, C. M., Montgomery, T., Ala-Mello, S., Kaitila, I., Winterpacht, A., Zabel, B., Frydman, M., Cole, W. G., Francomano, C. A., Lee, B. <strong>Mutation analysis of LMX1B gene in nail-patella syndrome patients.</strong> Am. J. Hum. Genet. 63: 1651-1658, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837817</a>] [<a href="https://doi.org/10.1086/302165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9837817">McIntosh et al. (1998)</a> demonstrated a splice site mutation, 672+1G-A, in the homeodomain of the LMX1B gene, resulting in loss of exon 4, a frameshift, and a premature termination codon. The mutation occurred in the same codon as another splice mutation (<a href="#0010">602575.0010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837817" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMX1B, 672, G-T, +1
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1427331961 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1427331961;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/rs1427331961?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=rs1427331961" 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=rs1427331961" 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=RCV000625602 OR RCV001860462" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000625602, RCV001860462" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000625602...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family in which 2 members had nail-patella syndrome (NPS; <a href="/entry/161200">161200</a>), <a href="#22" class="mim-tip-reference" title="McIntosh, I., Dreyer, S. D., Clough, M. V., Dunston, J. A., Eyaid, W., Roig, C. M., Montgomery, T., Ala-Mello, S., Kaitila, I., Winterpacht, A., Zabel, B., Frydman, M., Cole, W. G., Francomano, C. A., Lee, B. <strong>Mutation analysis of LMX1B gene in nail-patella syndrome patients.</strong> Am. J. Hum. Genet. 63: 1651-1658, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837817</a>] [<a href="https://doi.org/10.1086/302165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9837817">McIntosh et al. (1998)</a> demonstrated a splice site mutation, 672+1G-T, in the homeodomain of the LMX1B gene, which resulted in loss of exon 4, a frameshift, and a premature termination codon. The same nucleotide was involved as in another splice mutation, 672+1G-A (<a href="#0009">602575.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837817" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMX1B, ARG226TER
|
|
</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> rs121909492 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121909492;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/rs121909492?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=rs121909492" 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=rs121909492" 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=RCV000007425 OR RCV001380260" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007425, RCV001380260" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007425...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 affected members of a family with nail-patella syndrome (NPS; <a href="/entry/161200">161200</a>), <a href="#22" class="mim-tip-reference" title="McIntosh, I., Dreyer, S. D., Clough, M. V., Dunston, J. A., Eyaid, W., Roig, C. M., Montgomery, T., Ala-Mello, S., Kaitila, I., Winterpacht, A., Zabel, B., Frydman, M., Cole, W. G., Francomano, C. A., Lee, B. <strong>Mutation analysis of LMX1B gene in nail-patella syndrome patients.</strong> Am. J. Hum. Genet. 63: 1651-1658, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837817</a>] [<a href="https://doi.org/10.1086/302165" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9837817">McIntosh et al. (1998)</a> identified a 676C-T transition in the LMX1B gene, resulting in an arg226-to-ter substitution in the homeodomain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837817" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMX1B, 17-BP DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007426" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007426" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007426</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p><a href="#14" class="mim-tip-reference" title="Hamlington, J. D., Clough, M. V., Dunston, J. A., McIntosh, I. <strong>Deletion of a branch-point consensus sequence in the LMX1B gene causes exon skipping in a family with nail patella syndrome.</strong> Europ. J. Hum. Genet. 8: 311-314, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10854116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10854116</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200448" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10854116">Hamlington et al. (2000)</a> found that the basis of the nail-patella syndrome (NPS; <a href="/entry/161200">161200</a>) in an extensively affected kindred was a 17-bp deletion in intron 1 starting 37 bp upstream of exon 2 of the LMX1B gene. The deletion removed a recognition sequence for the restriction enzyme EagI; restriction digestion of PCR-amplified DNA from 14 affected and 11 unaffected members indicated that the deletion was found only in persons with NPS and was not found in 50 unrelated individuals from an unaffected control population. The deletion encompassed a consensus branchpoint sequence. RNA analysis demonstrated that deletion of the branchpoint sequence resulted in skipping of the downstream exon. <a href="#14" class="mim-tip-reference" title="Hamlington, J. D., Clough, M. V., Dunston, J. A., McIntosh, I. <strong>Deletion of a branch-point consensus sequence in the LMX1B gene causes exon skipping in a family with nail patella syndrome.</strong> Europ. J. Hum. Genet. 8: 311-314, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10854116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10854116</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200448" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10854116">Hamlington et al. (2000)</a> suggested a mechanism to explain this phenomenon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10854116" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMX1B, DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000007427" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007427" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007427</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated patients with nail-patella syndrome (NPS; <a href="/entry/161200">161200</a>), <a href="#1" class="mim-tip-reference" title="Bongers, E. M. H. F., de Wijs, I. J., Marcelis, C., Hoefsloot, L. H., Knoers, N. V. A. M. <strong>Identification of entire LMX1B gene deletions in nail patella syndrome: evidence for haploinsufficiency as the main pathogenic mechanism underlying dominant inheritance in man.</strong> Europ. J. Hum. Genet. 16: 1240-1244, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18414507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18414507</a>] [<a href="https://doi.org/10.1038/ejhg.2008.83" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18414507">Bongers et al. (2008)</a> identified a heterozygous deletion of the entire LMX1B gene. The deletion was de novo and limited to the LMX1B gene in 1 patient, whereas the deletion was inherited and included some flanking regions in the other patient. The phenotype was similar to other reported cases with point or truncating mutations. The findings confirmed that haploinsufficiency of LMX1B is the pathogenic mechanism in nail-patella syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18414507" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 FOCAL SEGMENTAL GLOMERULOSCLEROSIS 10</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMX1B, ARG246GLN
|
|
</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> rs1191455921 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1191455921;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/rs1191455921?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=rs1191455921" 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=rs1191455921" 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=RCV000594256 OR RCV001281185 OR RCV001328157 OR RCV001807647 OR RCV002476296 OR RCV003915707 OR RCV003994037" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000594256, RCV001281185, RCV001328157, RCV001807647, RCV002476296, RCV003915707, RCV003994037" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000594256...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 affected members of a large multigenerational family (family F) of European descent with focal segmental glomerulosclerosis-10 (FSGS10; <a href="/entry/256020">256020</a>), <a href="#3" class="mim-tip-reference" title="Boyer, O., Woerner, S., Yang, F., Oakeley, E. J., Linghu, B., Gribouval, O., Tete, M.-J., Duca, J. S., Klickstein, L., Damask, A. J., Szustakowski, J. D., Heibel, F., and 10 others. <strong>LMX1B mutations cause hereditary FSGS without extrarenal involvement.</strong> J. Am. Soc. Nephrol. 24: 1216-1222, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23687361/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23687361</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23687361[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/10.1681/ASN.2013020171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23687361">Boyer et al. (2013)</a> identified a heterozygous c.737G-A transition in exon 4 of the LMX1B gene, resulting in an arg246-to-gln (R246Q) substitution at a highly conserved residue in the homeodomain, which is important for DNA binding and necessary for transcriptional activation. The mutation, which was found by a combination of linkage analysis and exome sequencing, segregated with the disorder in the family. The variant was not present in the Exome Sequencing Project database. Two affected members of another European family (family V) with the same phenotype were also found to carry a heterozygous R246Q mutation. Functional studies of the variant and studies of patient cells were not performed, but <a href="#3" class="mim-tip-reference" title="Boyer, O., Woerner, S., Yang, F., Oakeley, E. J., Linghu, B., Gribouval, O., Tete, M.-J., Duca, J. S., Klickstein, L., Damask, A. J., Szustakowski, J. D., Heibel, F., and 10 others. <strong>LMX1B mutations cause hereditary FSGS without extrarenal involvement.</strong> J. Am. Soc. Nephrol. 24: 1216-1222, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23687361/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23687361</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23687361[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/10.1681/ASN.2013020171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23687361">Boyer et al. (2013)</a> hypothesized that the mutation might interfere with DNA binding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23687361" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 6-year-old Japanese girl with FSGS10, <a href="#16" class="mim-tip-reference" title="Isojima, T., Harita, Y., Furuyama, M., Sugawara, N., Ishizuka, K., Horita, S., Kajiho, Y., Miura, K., Igarashi, T., Hattori, M., Kitanaka, S. <strong>LMX1B mutation with residual transcriptional activity as a cause of isolated glomerulopathy.</strong> Nephrol. Dial. Transplant. 29: 81-88, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24042019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24042019</a>] [<a href="https://doi.org/10.1093/ndt/gft359" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24042019">Isojima et al. (2014)</a> identified a de novo heterozygous arg246-to-gln (R246Q) substitution in the LMX1B gene. The mutation, which was found by direct sequencing of the LMX1B gene, was not present in the dbSNP database or among Japanese controls. In vitro functional expression studies showed that the mutation partially impaired transcriptional activity of LMX1B compared to controls, but not to the extent as mutations associated with NPS. There was no evidence for a dominant-negative effect, and the authors postulated haploinsufficiency. Renal biopsy from the patient showed podocyte effacement, a thickened glomerular basement membrane (GBM) due to abnormal deposition of type III collagen, and altered expression of CD2AP (<a href="/entry/604241">604241</a>), which plays a role in podocyte development and cytoskeleton remodeling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24042019" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 18 affected members of 2 large multigenerational families (DUK35705 and DUK34319) with FSGS10, <a href="#12" class="mim-tip-reference" title="Hall, G., Lane, B., Chryst-Ladd, M., Wu, G., Lin, J.-J., Qin, X., Hauser, E. R., Gbadegesin, R. <strong>Dysregulation of WTI (-KTS) is associated with the kidney-specific effects of the LMX1B R246Q mutation.</strong> Sci. Rep. 7: 39933, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28059119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28059119</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28059119[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/srep39933" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28059119">Hall et al. (2017)</a> identified a heterozygous R246Q mutation in the LMX1B gene. The mutation, which was found by a combination of linkage analysis and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. In vitro functional expression studies in human podocyte cell lines transfected with the mutation showed altered expression of certain key podocyte genes, suggesting that the mutation may exert a haploinsufficiency effect on the transcriptional regulation of these genes. However, additional studies indicated that the R246Q mutation exerted a dominant-negative effect on certain WT1 (<a href="/entry/607102">607102</a>) isoforms, which may have also caused alterations in the expression of podocyte-related genes. <a href="#12" class="mim-tip-reference" title="Hall, G., Lane, B., Chryst-Ladd, M., Wu, G., Lin, J.-J., Qin, X., Hauser, E. R., Gbadegesin, R. <strong>Dysregulation of WTI (-KTS) is associated with the kidney-specific effects of the LMX1B R246Q mutation.</strong> Sci. Rep. 7: 39933, 2017. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28059119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28059119</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28059119[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/srep39933" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28059119">Hall et al. (2017)</a> noted that the renal glomerular phenotype observed in these patients includes a wide variety of light microscopic findings, including focal segmental glomerulosclerosis, minimal change disease, membranous nephropathy, and even immune complex glomerulonephritis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28059119" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#25" class="mim-tip-reference" title="Pinto e Vairo, F., Pichurin, P. N., Fervenza, F. C., Nasr, S. H., Mills, K., Schmitz, C. T., Klee, E. W., Herrmann, S. M. <strong>Nail-patella-like renal disease masquerading as Fabry disease on kidney biopsy: a case report.</strong> BMC Nephrol. 21: 341, 2020. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32791958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32791958</a>] [<a href="https://doi.org/10.1186/s12882-020-02012-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32791958">Pinto e Vairo et al. (2020)</a> identified a heterozygous c.737G-A transition (c.737G-A, NM_002316.3) in the LMX1B gene, resulting in a R246Q substitution, in a 65-year-old woman with FSGS10 and a family history of chronic kidney disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32791958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Lei, L., Oh, G., Sutherland, S., Abra, G., Higgins, J., Sibley, R., Troxell, M., Kambham, N. <strong>Myelin bodies in LMX1B-associated nephropathy: potential for misdiagnosis.</strong> Pediat. Nephrol. 35: 1647-1657, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32356190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32356190</a>] [<a href="https://doi.org/10.1007/s00467-020-04564-w" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32356190">Lei et al. (2020)</a> identified heterozygosity for the R246Q mutation in patients from 2 families with FSGS10. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32356190" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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 FOCAL SEGMENTAL GLOMERULOSCLEROSIS 10</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMX1B, ARG246PRO
|
|
</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> rs1191455921 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1191455921;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/rs1191455921?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=rs1191455921" 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=rs1191455921" 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=RCV001807651 OR RCV002260131" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001807651, RCV002260131" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001807651...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a father and daughter of European descent (family B) with focal segmental glomerulosclerosis-10 (FSGS10; <a href="/entry/256020">256020</a>), <a href="#3" class="mim-tip-reference" title="Boyer, O., Woerner, S., Yang, F., Oakeley, E. J., Linghu, B., Gribouval, O., Tete, M.-J., Duca, J. S., Klickstein, L., Damask, A. J., Szustakowski, J. D., Heibel, F., and 10 others. <strong>LMX1B mutations cause hereditary FSGS without extrarenal involvement.</strong> J. Am. Soc. Nephrol. 24: 1216-1222, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23687361/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23687361</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23687361[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/10.1681/ASN.2013020171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23687361">Boyer et al. (2013)</a> identified a heterozygous c.737G-C transversion in exon 4 of the LMX1B gene, resulting in an arg246-to-pro (R246P) substitution at a highly conserved residue in the homeodomain, which is important for DNA binding and necessary for transcriptional activation. The mutation, which was found by direct sequencing of the LMX1B gene, was not present in the Exome Sequencing Project database. This family was ascertained from a cohort of 73 unrelated families with a similar phenotype. Functional studies of the variant and studies of patient cells were not performed, but <a href="#3" class="mim-tip-reference" title="Boyer, O., Woerner, S., Yang, F., Oakeley, E. J., Linghu, B., Gribouval, O., Tete, M.-J., Duca, J. S., Klickstein, L., Damask, A. J., Szustakowski, J. D., Heibel, F., and 10 others. <strong>LMX1B mutations cause hereditary FSGS without extrarenal involvement.</strong> J. Am. Soc. Nephrol. 24: 1216-1222, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23687361/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23687361</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23687361[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/10.1681/ASN.2013020171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23687361">Boyer et al. (2013)</a> hypothesized that the mutation might interfere with DNA binding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23687361" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon 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="Bongers2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bongers, E. M. H. F., de Wijs, I. J., Marcelis, C., Hoefsloot, L. H., Knoers, N. V. A. M.
|
|
<strong>Identification of entire LMX1B gene deletions in nail patella syndrome: evidence for haploinsufficiency as the main pathogenic mechanism underlying dominant inheritance in man.</strong>
|
|
Europ. J. Hum. Genet. 16: 1240-1244, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18414507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18414507</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18414507" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ejhg.2008.83" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Bongers2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bongers, E. M. H. F., Huysmans, F. T., Levtchenko, E., de Rooy, J. W., Blickman, J. G., Admiraal, R. J. C., Huygen, P. L. M., Cruysberg, J. R. M., Toolens, P. A. M. P., Prins, J. B., Krabbe, P. F. M., Borm, G. F., Schoots, J., van Bokhoven, H., van Remortele, A. M. F., Hoefsloot, L. H., van Kampen, A., Knoers, N. V. A. M.
|
|
<strong>Genotype-phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy.</strong>
|
|
Europ. J. Hum. Genet. 13: 935-946, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15928687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15928687</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15928687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.ejhg.5201446" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Boyer2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Boyer, O., Woerner, S., Yang, F., Oakeley, E. J., Linghu, B., Gribouval, O., Tete, M.-J., Duca, J. S., Klickstein, L., Damask, A. J., Szustakowski, J. D., Heibel, F., and 10 others.
|
|
<strong>LMX1B mutations cause hereditary FSGS without extrarenal involvement.</strong>
|
|
J. Am. Soc. Nephrol. 24: 1216-1222, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23687361/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23687361</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23687361[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=23687361" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1681/ASN.2013020171" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Chen1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, H., Lun, Y., Ovchinnikov, D., Kokubo, H., Oberg, K. C., Pepicelli, C. V., Gan, L., Lee, B., Johnson, R. L.
|
|
<strong>Limb and kidney defects in Lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome.</strong>
|
|
Nature Genet. 19: 51-55, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590288</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590288" 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/ng0598-51" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Church1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Church, D. M., Stotler, C. J., Rutter, J. L., Murrell, J. R., Trofatter, J. A., Buckler, A. J.
|
|
<strong>Isolation of genes from complex sources of mammalian genomic DNA using exon amplification.</strong>
|
|
Nature Genet. 6: 98-105, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8136842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8136842</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8136842" 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/ng0194-98" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Clough1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Clough, M. V., Hamlington, J. D., McIntosh, I.
|
|
<strong>Restricted distribution of loss-of-function mutations within the LMX1B genes of nail-patella syndrome patients.</strong>
|
|
Hum. Mutat. 14: 459-465, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10571942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10571942</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10571942" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1098-1004(199912)14:6<459::AID-HUMU3>3.0.CO;2-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Ding2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ding, Y.-Q., Marklund, U., Yuan, W., Yin, J., Wegman, L., Ericson, J., Deneris, E., Johnson, R. L., Chen, Z.-F.
|
|
<strong>Lmx1b is essential for the development of serotonergic neurons.</strong>
|
|
Nature Neurosci. 6: 933-938, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12897786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12897786</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12897786" 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/nn1104" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Donovan2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Donovan, L. J., Spencer, W. C., Kitt, M. M., Eastman, B. A., Lobur, K. J., Jiao, K., Silver, J., Deneris, E. S.
|
|
<strong>Lmx1b is required at multiple stages to build expansive serotonergic axon architectures.</strong>
|
|
eLife 8: e48788, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31355748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31355748</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31355748[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=31355748" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.7554/eLife.48788" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Dreyer2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dreyer, S. D., Morello, R., German, M. S., Zabel, B., Winterpacht, A., Lunstrum, G. P., Horton, W. A., Oberg, K. C., Lee, B.
|
|
<strong>LMX1B transactivation and expression in nail-patella syndrome.</strong>
|
|
Hum. Molec. Genet. 9: 1067-1074, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10767331/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10767331</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10767331" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/9.7.1067" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Dreyer1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dreyer, S. D., Zhou, G., Baldini, A., Winterpacht, A., Zabel, B., Cole, W., Johnson, R. L., Lee, B.
|
|
<strong>Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome.</strong>
|
|
Nature Genet. 19: 47-50, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9590287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9590287</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9590287" 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/ng0598-47" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Dunston2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dunston, J. A., Hamlington, J. D., Zaveri, J., Sweeney, E., Sibbring, J., Tran, C., Malbroux, M., O'Neill, J. P., Mountford, R., McIntosh, I.
|
|
<strong>The human LMX1B gene: transcription unit, promoter, and pathogenic mutations.</strong>
|
|
Genomics 84: 565-576, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15498463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15498463</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15498463" 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.ygeno.2004.06.002" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Hall2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hall, G., Lane, B., Chryst-Ladd, M., Wu, G., Lin, J.-J., Qin, X., Hauser, E. R., Gbadegesin, R.
|
|
<strong>Dysregulation of WTI (-KTS) is associated with the kidney-specific effects of the LMX1B R246Q mutation.</strong>
|
|
Sci. Rep. 7: 39933, 2017. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28059119/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28059119</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28059119[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=28059119" 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/srep39933" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Hamano2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hamano, Y., Grunkemeyer, J. A., Sudhakar, A., Zeisberg, M., Cosgrove, D., Morello, R., Lee, B., Sugimoto, H., Kalluri, R.
|
|
<strong>Determinants of vascular permeability in the kidney glomerulus.</strong>
|
|
J. Biol. Chem. 277: 31154-31162, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12039968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12039968</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12039968" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M204806200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Hamlington2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hamlington, J. D., Clough, M. V., Dunston, J. A., McIntosh, I.
|
|
<strong>Deletion of a branch-point consensus sequence in the LMX1B gene causes exon skipping in a family with nail patella syndrome.</strong>
|
|
Europ. J. Hum. Genet. 8: 311-314, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10854116/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10854116</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10854116" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.ejhg.5200448" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Iannotti1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Iannotti, C. A., Inoue, H., Bernal, E., Aoki, M., Liu, l., Donis-Keller, H., German, M. S., Permutt, M. A.
|
|
<strong>Identification of a human LMX1 (LMX1.1)-related gene, LMX1.2: tissue-specific expression and linkage mapping on chromosome 9.</strong>
|
|
Genomics 46: 520-524, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9441763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9441763</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9441763" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1997.5075" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Isojima2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Isojima, T., Harita, Y., Furuyama, M., Sugawara, N., Ishizuka, K., Horita, S., Kajiho, Y., Miura, K., Igarashi, T., Hattori, M., Kitanaka, S.
|
|
<strong>LMX1B mutation with residual transcriptional activity as a cause of isolated glomerulopathy.</strong>
|
|
Nephrol. Dial. Transplant. 29: 81-88, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24042019/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24042019</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24042019" 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/ndt/gft359" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Johnson1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johnson, R. L., Tabin, C. J.
|
|
<strong>Molecular models for vertebrate limb development.</strong>
|
|
Cell 90: 979-990, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9323126/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9323126</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9323126" 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)80364-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Kania2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kania, A., Johnson, R. L., Jessell, T. M.
|
|
<strong>Coordinate roles for LIM homeobox genes in directing the dorsoventral trajectory of motor axons in the vertebrate limb.</strong>
|
|
Cell 102: 161-173, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10943837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10943837</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10943837" 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)00022-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Lei2020" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lei, L., Oh, G., Sutherland, S., Abra, G., Higgins, J., Sibley, R., Troxell, M., Kambham, N.
|
|
<strong>Myelin bodies in LMX1B-associated nephropathy: potential for misdiagnosis.</strong>
|
|
Pediat. Nephrol. 35: 1647-1657, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32356190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32356190</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32356190" 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/s00467-020-04564-w" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Lichter1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lichter, P. R., Richards, J. E., Downs, C. A., Stringham, H. M., Boehnke, M., Farley, F. A.
|
|
<strong>Cosegregation of open-angle glaucoma and the nail-patella syndrome.</strong>
|
|
Am. J. Ophthal. 124: 506-515, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9323941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9323941</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9323941" 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/s0002-9394(14)70866-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Marini2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Marini, M., Giacopelli, F., Seri, M., Ravazzolo, R.
|
|
<strong>Interaction of the LMX1B and PAX2 gene products suggests possible molecular basis of differential phenotypes in nail-patella syndrome.</strong>
|
|
Europ. J. Hum. Genet. 13: 789-792, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15785774/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15785774</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15785774" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.ejhg.5201405" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="McIntosh1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McIntosh, I., Dreyer, S. D., Clough, M. V., Dunston, J. A., Eyaid, W., Roig, C. M., Montgomery, T., Ala-Mello, S., Kaitila, I., Winterpacht, A., Zabel, B., Frydman, M., Cole, W. G., Francomano, C. A., Lee, B.
|
|
<strong>Mutation analysis of LMX1B gene in nail-patella syndrome patients.</strong>
|
|
Am. J. Hum. Genet. 63: 1651-1658, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837817</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837817" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302165" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Morello2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Morello, R., Zhou, G., Dreyer, S. D., Harvey, S. J., Ninomiya, Y., Thorner, P. S., Miner, J. H., Cole, W., Winterpacht, A., Zabel, B., Oberg, K. C., Lee, B.
|
|
<strong>Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome.</strong>
|
|
Nature Genet. 27: 205-208, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11175791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11175791</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11175791" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/84853" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Pilz1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pilz, A., Prohaska, R., Peters, J., Abbott, C.
|
|
<strong>Genetic linkage analysis of the Ak1, Col5a1, Epb7.2, Fpgs, Grp78, Pbx3, and Notch1 genes in the region of mouse chromosome 2 homologous to human chromosome 9q.</strong>
|
|
Genomics 21: 104-109, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8088777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8088777</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8088777" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/geno.1994.1230" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Pinto e Vairo2020" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pinto e Vairo, F., Pichurin, P. N., Fervenza, F. C., Nasr, S. H., Mills, K., Schmitz, C. T., Klee, E. W., Herrmann, S. M.
|
|
<strong>Nail-patella-like renal disease masquerading as Fabry disease on kidney biopsy: a case report.</strong>
|
|
BMC Nephrol. 21: 341, 2020. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32791958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32791958</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32791958" 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/s12882-020-02012-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Vogel1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vogel, A., Rodriguez, C., Warnken, W., Izpisua Belmonte, J. C.
|
|
<strong>Dorsal cell fate specified by chick Lmx1 during vertebrate limb development.</strong>
|
|
Nature 378: 716-720, 1995. Note: Erratum: Nature 379: 848 only, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7501017/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7501017</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7501017" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/378716a0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Vollrath1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vollrath, D., Jaramillo-Babb, V. L., Clough, M. V., McIntosh, I., Scott, K. M., Lichter, P. R., Richards, J. E.
|
|
<strong>Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome.</strong>
|
|
Hum. Molec. Genet. 7: 1091-1098, 1998. Erratum: Hum. Molec. Genet. 7: 1333 only, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9618165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9618165</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9618165" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/7.7.1091" 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">
|
|
Bao Lige - updated : 03/11/2022
|
|
</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">
|
|
Cassandra L. Kniffin - updated : 11/24/2020<br>Cassandra L. Kniffin - updated : 2/25/2009<br>Marla J. F. O'Neill - updated : 2/14/2006<br>Cassandra L. Kniffin - updated : 6/16/2005<br>Patricia A. Hartz - updated : 8/26/2004<br>Cassandra L. Kniffin - updated : 8/15/2003<br>Patricia A. Hartz - updated : 1/23/2003<br>Victor A. McKusick - updated : 1/25/2001<br>Victor A. McKusick - updated : 11/1/2000<br>Stylianos E. Antonarakis - updated : 8/4/2000<br>George E. Tiller - updated : 5/8/2000<br>Victor A. McKusick - updated : 12/11/1998<br>Sheryl A. Jankowski - updated : 8/11/1998<br>Victor A. McKusick - updated : 6/19/1998<br>Ada Hamosh - updated : 4/30/1998
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 4/27/1998
|
|
</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 : 07/25/2024
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 02/08/2024<br>carol : 01/09/2024<br>carol : 09/21/2022<br>mgross : 03/11/2022<br>carol : 12/15/2020<br>carol : 12/11/2020<br>alopez : 12/07/2020<br>ckniffin : 11/24/2020<br>terry : 03/14/2013<br>terry : 10/4/2012<br>wwang : 3/19/2009<br>ckniffin : 2/25/2009<br>alopez : 7/5/2007<br>wwang : 2/16/2006<br>terry : 2/14/2006<br>wwang : 7/7/2005<br>ckniffin : 6/16/2005<br>terry : 4/5/2005<br>mgross : 8/30/2004<br>mgross : 8/30/2004<br>terry : 8/26/2004<br>terry : 3/18/2004<br>alopez : 9/2/2003<br>carol : 8/18/2003<br>ckniffin : 8/15/2003<br>mgross : 1/23/2003<br>carol : 2/13/2002<br>alopez : 1/29/2001<br>terry : 1/25/2001<br>mcapotos : 11/8/2000<br>mcapotos : 11/3/2000<br>terry : 11/1/2000<br>mgross : 8/4/2000<br>alopez : 5/8/2000<br>mcapotos : 1/4/2000<br>jlewis : 6/24/1999<br>carol : 12/15/1998<br>terry : 12/11/1998<br>carol : 8/11/1998<br>carol : 6/22/1998<br>terry : 6/19/1998<br>alopez : 4/30/1998<br>alopez : 4/27/1998
|
|
</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> 602575
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
LIM HOMEOBOX TRANSCRIPTION FACTOR 1, BETA; LMX1B
|
|
|
|
</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">
|
|
LMX1.2
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: LMX1B</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 22199006, 236527004;
|
|
|
|
|
|
<strong>ICD10CM:</strong> Q87.2;
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 9q33.3
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 9:126,613,928-126,701,032 </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">
|
|
9q33.3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Focal segmental glomerulosclerosis 10
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
256020
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Nail-patella syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
161200
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The LMX1B gene encodes a transcription factor that belongs to the LIM-homeodomain family of proteins. These proteins are vital for the normal development of dorsal limb structures in vertebrates, components of the renal glomerular filtration barrier, and the anterior segment of the eye (summary by Isojima et al., 2014 and Hall et al., 2017). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>LIM-homeodomain proteins are characterized by the presence of 2 tandem cysteine/histidine-rich, zinc-binding LIM domains. LMX1 (600298), a LIM-homeodomain-containing protein expressed selectively in insulin-producing beta cell lines, has been shown to activate insulin gene transcription. Iannotti et al. (1997) searched a human EST database with hamster LMX1 sequences to isolate the human LMX1 gene for physical mapping and identification of polymorphic markers. They obtained 2 highly homologous sequences, originally identified by exon trapping of human chromosome 9 (Church et al., 1994), and showed that the ESTs represented a closely related but distinct gene, designated LMX1.2 or LMX1B. Iannotti et al. (1997) found that the sequence of a 482-bp RT-PCR product of human LMX1B and that of the corresponding hamster LMX1 were 92% identical at the amino acid level and that the DNA-binding domains were 100% identical at the amino acid level. They used the human chromosome 9 EST to rescreen the hamster pancreatic islet beta cell library and isolated hamster LMX1B. Sequence comparison suggested that human and hamster LMX1B and chicken LMX1 (Vogel et al., 1995) are homologs of the same gene, which is closely related to hamster LMX1. Iannotti et al. (1997) performed RT-PCR analysis on total RNAs from 11 adult human tissues and found expression of LMX1B in most of the tissues, with highest levels in testis, thyroid, duodenum, skeletal muscle, and pancreatic islets. </p><p>Dreyer et al. (1998) isolated an LMX1B cDNA and stated that the open reading frame encodes 372 amino acids and contains 2 N-terminal zinc-binding LIM domains, 1 homeodomain, and a C-terminal glutamine-rich domain. The mouse and human sequences are 99% identical. Northern blot analysis of RNA from human fetal and adult tissues revealed a major 7.0-kb transcript abundant in fetal and adult kidney. </p><p>Dunston et al. (2004) identified an upstream start codon in the LMX1B gene that is in-frame with the previously determined open reading frame, extending the protein to 395 or 402 amino acids, depending on exon 7 splice-site selection. Upstream of this start codon are 2 additional short open reading frames. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Dreyer et al. (2000) noted strong expression of Lmx1b in dorsal mesenchymal tissues (precursors of muscle, tendons, joints, and patella) and also in anterior structures of the murine limb by in situ hybridization, mimicking the anterior to posterior gradient of joint and nail dysplasia observed in patients with nail-patella syndrome (NPS; 161200). Transfection studies showed that both the LIM domain-interacting protein LDB1 (603451) and the helix-loop-helix protein E47/shPan1 (147141), regulated LMX1B action. While cotransfections of E47/shPan1 with LMX1B resulted in a synergistic effect on reporter activity, LDB1 downregulated LMX1B-mediated transactivation irrespective of E47/shPan1. Mutant LMX1B proteins containing human mutations affecting each of the helices or the N-terminal arm of the homeodomain abolished transactivation, while LIM B domain and truncation mutations retained residual activity. These mutations failed to act in a dominant-negative manner on wildtype LMX1B in mixing studies, thereby further supporting haploinsufficiency as the mechanism underlying NPS pathogenesis. </p><p>Kania et al. (2000) showed that Lim1 (LHX1; 601999) and Lmx1b control the initial trajectory of motor axons in the developing mammalian limb. The expression of Lim1 by a lateral set of lateral motor column (LMC) neurons ensured that their axons selected a dorsal trajectory in the limb. In a complementary manner, the expression of Lmx1b by dorsal limb mesenchymal cells was shown to control the dorsal and ventral axonal trajectories of medial and lateral LMC neurons. In the absence of these 2 proteins, motor axons appeared to select dorsal and ventral trajectories at random. Thus, LIM homeodomain proteins act within motor neurons and cells that guide motor axons to establish the fidelity of a binary choice in axonal trajectory. </p><p>Morello et al. (2001) reported that, in Lmx1b -/- mice, expression of both the alpha-3 and alpha-4 chains of type IV collagen is strongly diminished in glomerular basement membrane, whereas that of alpha-1, alpha-2, and alpha-5 type IV collagen is unchanged. Moreover, LMX1B binds specifically to a putative enhancer sequence in intron 1 of both mouse and human COL4A4 (120131) and upregulates reporter constructs containing this enhancer-like sequence. These data indicated that LMX1B directly regulates the coordinated expression of the alpha-3(IV) and alpha-4(IV) collagen required for normal GBM morphogenesis and that its dysregulation in glomerular basement membrane contributes to the renal pathology and nephrosis in nail-patella syndrome. </p><p>Ding et al. (2003) presented evidence suggesting that Lmx1b is required for the development of 5-HT (5-hydroxytryptamine) neurons in the central nervous system in mice, and that Lmx1b acts as a critical mediator downstream of Shh (600725) and Nkx2.2 (604612) in a signaling cascade to direct specification and/or differentiation of 5-HT neurons. </p><p>Johnson and Tabin (1997) reviewed the role of this gene, which they referred to as LMX1, and others in limb development. </p><p>Marini et al. (2005) demonstrated an interaction between LMX1B and the PAX2 gene (167409) using both direct yeast 2-hybrid assays and coimmunoprecipitation studies. Experiments with deletion constructs indicated that the LMX1B homeodomain interacted with the PAX2 homeodomain. Marini et al. (2005) suggested that PAX2 may be a modifier gene in NPS. </p><p>By analyzing Lmx1b conditional knockout mice, Donovan et al. (2019) showed that Lmx1b was required for formation of both ascending and descending 5-HT axon projection pathways, as Lmx1b deficiency in 5-HT neurons resulted in delayed primary pathway formation followed by a profound failure of ascending axons to selectively route into preexisting fiber tracts. Stage-specific knockdown of Lmx1b at different early postnatal timepoints of mouse development revealed that Lmx1b acted temporally at successive stages to control 5-HT axon primary outgrowth, selective routing, and terminal arborization. RNA-sequencing analysis revealed that Lmx1b controlled axon-related transcriptomes and identified an ascending-specific axonal Lmx1b-to-Pet1 (FEV; 607150) regulatory cascade. Lmx1b acted through Pet1 continually over an extended postnatal period to control stage-specific gene expression and to generate both early and late 5-HT terminal arbor patterns in different forebrain regions. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Vollrath et al. (1998) determined that the LMX1B gene contains at least 8 exons in a genomic region with high CG content. </p><p>Dunston et al. (2004) determined that the LMX1B transcription start site is located within a cluster of 4 CpG islands and is not associated with a consensus TATA box. The 5-prime UTR contains CCAAT boxes, a basic transcription element, and binding sites for SP1 (189906), OCT1 (164175), and TCF (142410)/LEF1 (153245). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By PCR analysis of rodent-human somatic cell hybrid DNA, Iannotti et al. (1997) confirmed the mapping of the LMX1 gene to chromosome 1 and the LMX1B gene to chromosome 9. The authors identified a simple sequence repeat polymorphisms in a P1 genomic clone containing LMX1B and used the resulting polymorphic markers to construct a genetic linkage map that localized LMX1B to 9q32-q34.1. </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>Nail-Patella Syndrome</em></strong></p><p>
|
|
Dreyer et al. (1998) identified de novo heterozygous mutations in the LMX1B gene (161200.0001-161200.0003) in 3 unrelated patients with nail-patella syndrome (NPS; 161200). Functional studies showed that one of these mutations disrupted sequence-specific DNA binding, while the other 2 mutations resulted in premature termination of translation. All 3 patients had presented in early childhood with nail dysplasia involving at least the thumbs, elbow stiffness with limitation of pronation and supination, and poorly ossified, malformed patellae. They also had classic radiographic features, including iliac flaring and iliac horns. </p><p>Vollrath et al. (1998) sequenced a large segment of LMX1B from the genomic DNA of probands from 4 families with nail-patella syndrome and open angle glaucoma (OAG; see 137760) and identified 4 mutations: 2 stop codons, a deletion causing a frameshift, and a missense mutation in a functionally important residue. The presence of these putative loss-of-function mutations in the DNA of individuals with NPS indicated that haploinsufficiency of LMX1B underlies this disorder. The results helped explain the high degree of variability in the NPS phenotype, and suggested that the skeletal defects in NPS are a result of the diminished dorsoventral patterning activity of LMX1B protein during limb development. The results further suggested that the NPS and OAG phenotypes in the families studied resulted from mutations in a single gene, LMX1B. Although renal abnormalities accompanying NPS were well known, the cosegregation of open angle glaucoma with NPS in other families (Lichter et al., 1997) was a less well-known finding. </p><p>McIntosh et al. (1998) screened 41 NPS families for LMX1B mutations. A total of 25 mutations were identified in 37 families. The nature of the mutations supported the hypothesis that NPS is the result of haploinsufficiency for LMX1B. There was no evidence of correlation between aspects of the NPS phenotype and specific mutations. </p><p>Clough et al. (1999) stated that a total of 64 point mutations and small deletions or insertions in the LMX1B gene had been reported and that they were concentrated within either the LIM or homeodomains. No nail-patella syndrome mutations had been observed within the C-terminal third of the coding sequence, suggesting that mutations in this region are not inactivating. These findings supported the hypothesis that NPS results from a 50% reduction in LMX1B function via a reduction in synthesis, disruption of secondary structure, or failure to bind DNA. </p><p>Dunston et al. (2004) identified 47 additional mutations within the coding region of the LMX1B gene, as well as 9 deletions of large portions of the gene. No mutations were identified in the promoter or in highly conserved intronic sequences. </p><p>Using multiplex ligation-probe amplification (MLPA) analysis, Bongers et al. (2008) identified a heterozygous deletion of the entire LMX1B gene (602575.0013) in 2 unrelated patients with nail-patella syndrome. The phenotype was similar to other reported cases with point or truncating mutations. The findings confirmed that haploinsufficiency of LMX1B is the pathogenic mechanism in nail-patella syndrome. </p><p><strong><em>Focal Segmental Glomerulosclerosis 10</em></strong></p><p>
|
|
In 5 affected members of a large multigenerational family (family F) with focal segmental glomerulosclerosis-10 (FSGS10; 256020), Boyer et al. (2013) identified a heterozygous missense mutation in the LMX1B gene (R246Q; 602575.0014). The mutation, which was found by a combination of linkage analysis and exome sequencing, segregated with the disorder in the family. Direct sequencing of the LMX1B gene in a cohort of 73 unrelated families with a similar phenotype identified a heterozygous R246Q mutation in an affected mother and daughter (family V) and a heterozygous R246P (602575.0015) mutation in an affected father and daughter (family B). Neither variant was present in the Exome Sequencing Project. Functional studies of the variants and studies of patient cells were not performed, but Boyer et al. (2013) noted that residue R246 is highly conserved and located in the homeobox domain, which is important for DNA binding and transcriptional activation. </p><p>In a 6-year-old Japanese girl with FSGS10, Isojima et al. (2014) identified a de novo heterozygous R246Q substitution in the LMX1B gene. The mutation, which was found by direct sequencing of the LMX1B gene, was not present in the dbSNP database or among Japanese controls. In vitro functional expression studies showed that the mutation partially impaired transcriptional activity of LMX1B compared to controls, but not to the extent as mutations associated with NPS. There was no evidence for a dominant-negative effect, and the authors postulated haploinsufficiency. Renal biopsy from the patient showed podocyte effacement, a thickened glomerular basement membrane (GBM) due to abnormal deposition of type III collagen, and altered expression of CD2AP (604241), which plays a role in podocyte development and cytoskeleton remodeling. </p><p>In 18 affected members from 2 large multigenerational families (DUK35705 and DUK34319) with FSGS10, Hall et al. (2017) identified a heterozygous R246Q mutation in the LMX1B gene. The mutation, which was found by a combination of linkage analysis and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. In vitro functional expression studies in human podocyte cell lines transfected with the mutation showed altered expression of certain key podocyte genes, suggesting that the mutation may exert a haploinsufficiency effect on the transcriptional regulation of these genes. However, additional studies indicated that the R246Q mutation exerted a dominant-negative effect on certain WT1 (607102) isoforms, which may have also caused alterations in the expression of podocyte-related genes. Hall et al. (2017) noted that the renal glomerular phenotype observed in these patients includes a wide variety of light microscopic findings, including focal segmental glomerulosclerosis, minimal change disease, membranous nephropathy, and even immune complex glomerulonephritis. </p><p>A heterozygous R246Q mutation was identified in patients with FSGS10 by Lei et al. (2020) and Pinto e Vairo et al. (2020). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Bongers et al. (2005) performed LMX1B mutation analysis and comprehensive examinations in 106 subjects from 32 NPS families and found that individuals with an LMXB1 mutation located in the homeodomain showed significantly more frequent and higher values of nephropathy and proteinuria than subjects with mutations in the LIM domains. No clear genotype-phenotype association was apparent for extrarenal manifestations. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Dorsoventral limb patterning in vertebrates is controlled by the LIM-homeodomain protein Lmx1b, which is expressed in a spatially and temporally restricted manner along the dorsoventral limb axis (Vogel et al., 1995). Chen et al. (1998) described a phenotype resulting from targeted disruption of Lmx1b in mice. The results demonstrated that Lmx1b is essential for the specification of dorsal limb fate at both the zeugopodal and autopodal levels with prominent phenotypes including absence of nails and patellae. Using an interspecific backcross panel, Pilz et al. (1994) mapped the Lmx1b gene to the distal portion of mouse chromosome 2 in a region syntenic to human 9q34, where the nail-patella syndrome gene is located. Furthermore, kidneys of Lmx1b mutant mice exhibited pathologic changes similar to those observed in nail-patella syndrome. </p><p>Hamano et al. (2002) characterized the renal defects of mice deficient in Lmx1b, which controls the expression of several glomerulus-specific proteins. Lmx1b-null mice died immediately after birth with massive glomerular vascular leaks. Glomerular basement membranes of these mice showed altered architecture, reduced expression of the type IV collagens alpha-3 (120070) and alpha-4 (COL4A4), and altered expression of the slit diaphragm proteins nephrin (602716) and podocin (604766). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>15 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMX1B, ASN269LYS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121909486,
|
|
|
|
|
|
gnomAD: rs121909486,
|
|
|
|
|
|
ClinVar: RCV000007415, RCV001380261, RCV005049319
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with nail-patella syndrome (NPS; 161200) who presented at 5 years of age with elbow contractures without evidence of ocular or renal abnormalities, Dreyer et al. (1998) found a C-to-A transversion in the LMX1B gene that resulted in substitution of lysine for asparagine at amino acid position 246. </p><p>Dunston et al. (2004) identified an upstream start codon in-frame with the published open reading frame of the LMX1B gene, revealing an additional 23 amino acids in-frame with the reported start codon; thus, this mutation results in an asn269-to-lys (N269K) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMX1B, ARG221TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121909487,
|
|
|
|
|
|
|
|
ClinVar: RCV000007416, RCV001388091
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with typical nail-patella syndrome (NPS; 161200), who presented at 6 years with joint stiffness and irregular pigmentation of the iris, but without evidence of kidney dysfunction, Dreyer et al. (1998) found a C-to-T transition in the LMX1B gene that resulted in an arg198-to-ter substitution was predicted to cause premature termination of the polypeptide with abolition of both the homeodomain and the putative glutamine-rich activation domain. </p><p>Dunston et al. (2004) identified an upstream start codon in-frame with the published open reading frame of the LMX1B gene, revealing an additional 23 amino acids in-frame with the reported start codon; thus, this mutation results in an arg221-to-ter (R221X) substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMX1B, 1-BP INS, 713A
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000007417
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with classic features of nail-patella syndrome (NPS; 161200) who presented in infancy with proteinuria and ultimately developed nephrotic syndrome, Dreyer et al. (1998) identified a single nucleotide A insertion in the LMX1B gene, resulting in a frameshift mutation disrupting the reading frame at codon 233 in the homeodomain and predicting translation termination at codon 327 in the glutamine-rich C-terminal domain (713insA). Light microscopic analysis of a kidney biopsy from this patient showed only mild interstitial fibrosis; ultrastructural studies revealed thickened and split glomerular basement membranes, and fusion and hyperplasia of foot processes similar to that identified in Lmx1b -/- mice. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMX1B, CYS95PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121909488,
|
|
|
|
|
|
|
|
ClinVar: RCV000007418
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-generation family (UM:47) of German ancestry, Vollrath et al. (1998) found typical features of nail-patella syndrome (NPS; 161200) in all members who had open angle glaucoma, as well as in members who did not have POAG. Proteinuria was not present. Age at onset of glaucoma ranged from 18 to 41 years (mean, 32 years). The proband was found to be heterozygous for a G-to-T transversion in exon 3 of the LMX1B gene that resulted in a cys95-to-phe amino acid substitution in the LIM2 domain of the protein. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMX1B, 2-BP DEL, 233TG
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000007419, RCV002512873
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-generation family (UM:65) of French and Irish ancestry, Vollrath et al. (1998) found that the proband and 6 other individuals with glaucoma also had nail-patella syndrome (NPS; 161200). Age at onset of glaucoma ranged from birth to 54 years (mean, 24 years). Proteinuria was not found in family members who were screened, but medical records indicated that the proband's mother had proteinuria and kidney disease. The proband of family UM:65 was heterozygous for a 2-bp deletion in exon 2 (233delTG) of the LMX1B gene, predicting a severely truncated protein that lacks part of the LIM1 domain and all of the LIM2 and homeodomains, and contains a stretch of 44 N-terminal amino acid residues generated from an incorrect reading frame. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMX1B, GLN59TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121909489,
|
|
|
|
|
|
|
|
ClinVar: RCV000007420, RCV000760427, RCV005049320
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Vollrath et al. (1998) reported that members of family UM:68 with nail-patella syndrome (NPS; 161200) and open angle glaucoma had features of NPS that were said to have come from a Cherokee Indian ancestor. Age at onset of OAG ranged from 40 to 77 years (mean, approximately 56 years). In contrast to the other 3 families studied by Vollrath et al. (1998), all of the individuals with NPS in UM:68 were reported to have proteinuria. The proband of UM:68 was heterozygous for a C-to-T transition in exon 2 of the LMX1B gene that created a premature stop codon (gln59 to ter). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMX1B, ARG208TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121909490,
|
|
|
|
|
|
gnomAD: rs121909490,
|
|
|
|
|
|
ClinVar: RCV000007421, RCV000414681, RCV004639120
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Vollrath et al. (1998) described an LMX1B mutation, arg208 to ter, as the cause of nail-patella syndrome (NPS; 161200) and open angle glaucoma in a Caucasian family (UM:310). No proteinuria was known in the family. As in the other families studied by Vollrath et al. (1998), the severity of fingernail anomalies ranged from mild ridging to hypoplasia and aplasia. Elbow mobility was likewise variable. Age at onset of glaucoma ranged from 40 to 50 years (mean, 45 years). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMX1B, ARG200GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121909491,
|
|
|
|
|
|
|
|
ClinVar: RCV000007422, RCV001388092, RCV004748508, RCV005042000
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>McIntosh et al. (1998) described a 599G-A transition in the LM1B gene, resulting in an arg200-to-gln amino acid substitution in the homeodomain, in 5 presumably unrelated families with nail-patella syndrome (NPS; 161200). The mutation ablated a MspI restriction site. Putatively the gene had an effect on DNA binding. The recurrence of this mutation was not unexpected, since it was the result of a transition at a CpG dinucleotide. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMX1B, 672, G-A, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1427331961,
|
|
|
|
|
|
gnomAD: rs1427331961,
|
|
|
|
|
|
ClinVar: RCV000007423
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family in which 3 members had nail-patella syndrome (NPS; 161200), McIntosh et al. (1998) demonstrated a splice site mutation, 672+1G-A, in the homeodomain of the LMX1B gene, resulting in loss of exon 4, a frameshift, and a premature termination codon. The mutation occurred in the same codon as another splice mutation (602575.0010). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMX1B, 672, G-T, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1427331961,
|
|
|
|
|
|
gnomAD: rs1427331961,
|
|
|
|
|
|
ClinVar: RCV000625602, RCV001860462
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family in which 2 members had nail-patella syndrome (NPS; 161200), McIntosh et al. (1998) demonstrated a splice site mutation, 672+1G-T, in the homeodomain of the LMX1B gene, which resulted in loss of exon 4, a frameshift, and a premature termination codon. The same nucleotide was involved as in another splice mutation, 672+1G-A (602575.0009). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMX1B, ARG226TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121909492,
|
|
|
|
|
|
gnomAD: rs121909492,
|
|
|
|
|
|
ClinVar: RCV000007425, RCV001380260
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 affected members of a family with nail-patella syndrome (NPS; 161200), McIntosh et al. (1998) identified a 676C-T transition in the LMX1B gene, resulting in an arg226-to-ter substitution in the homeodomain. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMX1B, 17-BP DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000007426
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Hamlington et al. (2000) found that the basis of the nail-patella syndrome (NPS; 161200) in an extensively affected kindred was a 17-bp deletion in intron 1 starting 37 bp upstream of exon 2 of the LMX1B gene. The deletion removed a recognition sequence for the restriction enzyme EagI; restriction digestion of PCR-amplified DNA from 14 affected and 11 unaffected members indicated that the deletion was found only in persons with NPS and was not found in 50 unrelated individuals from an unaffected control population. The deletion encompassed a consensus branchpoint sequence. RNA analysis demonstrated that deletion of the branchpoint sequence resulted in skipping of the downstream exon. Hamlington et al. (2000) suggested a mechanism to explain this phenomenon. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 NAIL-PATELLA SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMX1B, DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000007427
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated patients with nail-patella syndrome (NPS; 161200), Bongers et al. (2008) identified a heterozygous deletion of the entire LMX1B gene. The deletion was de novo and limited to the LMX1B gene in 1 patient, whereas the deletion was inherited and included some flanking regions in the other patient. The phenotype was similar to other reported cases with point or truncating mutations. The findings confirmed that haploinsufficiency of LMX1B is the pathogenic mechanism in nail-patella syndrome. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 FOCAL SEGMENTAL GLOMERULOSCLEROSIS 10</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMX1B, ARG246GLN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1191455921,
|
|
|
|
|
|
gnomAD: rs1191455921,
|
|
|
|
|
|
ClinVar: RCV000594256, RCV001281185, RCV001328157, RCV001807647, RCV002476296, RCV003915707, RCV003994037
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 affected members of a large multigenerational family (family F) of European descent with focal segmental glomerulosclerosis-10 (FSGS10; 256020), Boyer et al. (2013) identified a heterozygous c.737G-A transition in exon 4 of the LMX1B gene, resulting in an arg246-to-gln (R246Q) substitution at a highly conserved residue in the homeodomain, which is important for DNA binding and necessary for transcriptional activation. The mutation, which was found by a combination of linkage analysis and exome sequencing, segregated with the disorder in the family. The variant was not present in the Exome Sequencing Project database. Two affected members of another European family (family V) with the same phenotype were also found to carry a heterozygous R246Q mutation. Functional studies of the variant and studies of patient cells were not performed, but Boyer et al. (2013) hypothesized that the mutation might interfere with DNA binding. </p><p>In a 6-year-old Japanese girl with FSGS10, Isojima et al. (2014) identified a de novo heterozygous arg246-to-gln (R246Q) substitution in the LMX1B gene. The mutation, which was found by direct sequencing of the LMX1B gene, was not present in the dbSNP database or among Japanese controls. In vitro functional expression studies showed that the mutation partially impaired transcriptional activity of LMX1B compared to controls, but not to the extent as mutations associated with NPS. There was no evidence for a dominant-negative effect, and the authors postulated haploinsufficiency. Renal biopsy from the patient showed podocyte effacement, a thickened glomerular basement membrane (GBM) due to abnormal deposition of type III collagen, and altered expression of CD2AP (604241), which plays a role in podocyte development and cytoskeleton remodeling. </p><p>In 18 affected members of 2 large multigenerational families (DUK35705 and DUK34319) with FSGS10, Hall et al. (2017) identified a heterozygous R246Q mutation in the LMX1B gene. The mutation, which was found by a combination of linkage analysis and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. In vitro functional expression studies in human podocyte cell lines transfected with the mutation showed altered expression of certain key podocyte genes, suggesting that the mutation may exert a haploinsufficiency effect on the transcriptional regulation of these genes. However, additional studies indicated that the R246Q mutation exerted a dominant-negative effect on certain WT1 (607102) isoforms, which may have also caused alterations in the expression of podocyte-related genes. Hall et al. (2017) noted that the renal glomerular phenotype observed in these patients includes a wide variety of light microscopic findings, including focal segmental glomerulosclerosis, minimal change disease, membranous nephropathy, and even immune complex glomerulonephritis. </p><p>Pinto e Vairo et al. (2020) identified a heterozygous c.737G-A transition (c.737G-A, NM_002316.3) in the LMX1B gene, resulting in a R246Q substitution, in a 65-year-old woman with FSGS10 and a family history of chronic kidney disease. </p><p>Lei et al. (2020) identified heterozygosity for the R246Q mutation in patients from 2 families with FSGS10. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 FOCAL SEGMENTAL GLOMERULOSCLEROSIS 10</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMX1B, ARG246PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1191455921,
|
|
|
|
|
|
gnomAD: rs1191455921,
|
|
|
|
|
|
ClinVar: RCV001807651, RCV002260131
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a father and daughter of European descent (family B) with focal segmental glomerulosclerosis-10 (FSGS10; 256020), Boyer et al. (2013) identified a heterozygous c.737G-C transversion in exon 4 of the LMX1B gene, resulting in an arg246-to-pro (R246P) substitution at a highly conserved residue in the homeodomain, which is important for DNA binding and necessary for transcriptional activation. The mutation, which was found by direct sequencing of the LMX1B gene, was not present in the Exome Sequencing Project database. This family was ascertained from a cohort of 73 unrelated families with a similar phenotype. Functional studies of the variant and studies of patient cells were not performed, but Boyer et al. (2013) hypothesized that the mutation might interfere with DNA binding. </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">
|
|
Bongers, E. M. H. F., de Wijs, I. J., Marcelis, C., Hoefsloot, L. H., Knoers, N. V. A. M.
|
|
<strong>Identification of entire LMX1B gene deletions in nail patella syndrome: evidence for haploinsufficiency as the main pathogenic mechanism underlying dominant inheritance in man.</strong>
|
|
Europ. J. Hum. Genet. 16: 1240-1244, 2008.
|
|
|
|
|
|
[PubMed: 18414507]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ejhg.2008.83]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bongers, E. M. H. F., Huysmans, F. T., Levtchenko, E., de Rooy, J. W., Blickman, J. G., Admiraal, R. J. C., Huygen, P. L. M., Cruysberg, J. R. M., Toolens, P. A. M. P., Prins, J. B., Krabbe, P. F. M., Borm, G. F., Schoots, J., van Bokhoven, H., van Remortele, A. M. F., Hoefsloot, L. H., van Kampen, A., Knoers, N. V. A. M.
|
|
<strong>Genotype-phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy.</strong>
|
|
Europ. J. Hum. Genet. 13: 935-946, 2005.
|
|
|
|
|
|
[PubMed: 15928687]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5201446]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Boyer, O., Woerner, S., Yang, F., Oakeley, E. J., Linghu, B., Gribouval, O., Tete, M.-J., Duca, J. S., Klickstein, L., Damask, A. J., Szustakowski, J. D., Heibel, F., and 10 others.
|
|
<strong>LMX1B mutations cause hereditary FSGS without extrarenal involvement.</strong>
|
|
J. Am. Soc. Nephrol. 24: 1216-1222, 2013.
|
|
|
|
|
|
[PubMed: 23687361]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1681/ASN.2013020171]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, H., Lun, Y., Ovchinnikov, D., Kokubo, H., Oberg, K. C., Pepicelli, C. V., Gan, L., Lee, B., Johnson, R. L.
|
|
<strong>Limb and kidney defects in Lmx1b mutant mice suggest an involvement of LMX1B in human nail patella syndrome.</strong>
|
|
Nature Genet. 19: 51-55, 1998.
|
|
|
|
|
|
[PubMed: 9590288]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0598-51]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Church, D. M., Stotler, C. J., Rutter, J. L., Murrell, J. R., Trofatter, J. A., Buckler, A. J.
|
|
<strong>Isolation of genes from complex sources of mammalian genomic DNA using exon amplification.</strong>
|
|
Nature Genet. 6: 98-105, 1994.
|
|
|
|
|
|
[PubMed: 8136842]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0194-98]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Clough, M. V., Hamlington, J. D., McIntosh, I.
|
|
<strong>Restricted distribution of loss-of-function mutations within the LMX1B genes of nail-patella syndrome patients.</strong>
|
|
Hum. Mutat. 14: 459-465, 1999.
|
|
|
|
|
|
[PubMed: 10571942]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(199912)14:6<459::AID-HUMU3>3.0.CO;2-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ding, Y.-Q., Marklund, U., Yuan, W., Yin, J., Wegman, L., Ericson, J., Deneris, E., Johnson, R. L., Chen, Z.-F.
|
|
<strong>Lmx1b is essential for the development of serotonergic neurons.</strong>
|
|
Nature Neurosci. 6: 933-938, 2003.
|
|
|
|
|
|
[PubMed: 12897786]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nn1104]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Donovan, L. J., Spencer, W. C., Kitt, M. M., Eastman, B. A., Lobur, K. J., Jiao, K., Silver, J., Deneris, E. S.
|
|
<strong>Lmx1b is required at multiple stages to build expansive serotonergic axon architectures.</strong>
|
|
eLife 8: e48788, 2019.
|
|
|
|
|
|
[PubMed: 31355748]
|
|
|
|
|
|
[Full Text: https://doi.org/10.7554/eLife.48788]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dreyer, S. D., Morello, R., German, M. S., Zabel, B., Winterpacht, A., Lunstrum, G. P., Horton, W. A., Oberg, K. C., Lee, B.
|
|
<strong>LMX1B transactivation and expression in nail-patella syndrome.</strong>
|
|
Hum. Molec. Genet. 9: 1067-1074, 2000.
|
|
|
|
|
|
[PubMed: 10767331]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/9.7.1067]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dreyer, S. D., Zhou, G., Baldini, A., Winterpacht, A., Zabel, B., Cole, W., Johnson, R. L., Lee, B.
|
|
<strong>Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome.</strong>
|
|
Nature Genet. 19: 47-50, 1998.
|
|
|
|
|
|
[PubMed: 9590287]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0598-47]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dunston, J. A., Hamlington, J. D., Zaveri, J., Sweeney, E., Sibbring, J., Tran, C., Malbroux, M., O'Neill, J. P., Mountford, R., McIntosh, I.
|
|
<strong>The human LMX1B gene: transcription unit, promoter, and pathogenic mutations.</strong>
|
|
Genomics 84: 565-576, 2004.
|
|
|
|
|
|
[PubMed: 15498463]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ygeno.2004.06.002]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hall, G., Lane, B., Chryst-Ladd, M., Wu, G., Lin, J.-J., Qin, X., Hauser, E. R., Gbadegesin, R.
|
|
<strong>Dysregulation of WTI (-KTS) is associated with the kidney-specific effects of the LMX1B R246Q mutation.</strong>
|
|
Sci. Rep. 7: 39933, 2017. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 28059119]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/srep39933]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hamano, Y., Grunkemeyer, J. A., Sudhakar, A., Zeisberg, M., Cosgrove, D., Morello, R., Lee, B., Sugimoto, H., Kalluri, R.
|
|
<strong>Determinants of vascular permeability in the kidney glomerulus.</strong>
|
|
J. Biol. Chem. 277: 31154-31162, 2002.
|
|
|
|
|
|
[PubMed: 12039968]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M204806200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hamlington, J. D., Clough, M. V., Dunston, J. A., McIntosh, I.
|
|
<strong>Deletion of a branch-point consensus sequence in the LMX1B gene causes exon skipping in a family with nail patella syndrome.</strong>
|
|
Europ. J. Hum. Genet. 8: 311-314, 2000.
|
|
|
|
|
|
[PubMed: 10854116]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5200448]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Iannotti, C. A., Inoue, H., Bernal, E., Aoki, M., Liu, l., Donis-Keller, H., German, M. S., Permutt, M. A.
|
|
<strong>Identification of a human LMX1 (LMX1.1)-related gene, LMX1.2: tissue-specific expression and linkage mapping on chromosome 9.</strong>
|
|
Genomics 46: 520-524, 1997.
|
|
|
|
|
|
[PubMed: 9441763]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1997.5075]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Isojima, T., Harita, Y., Furuyama, M., Sugawara, N., Ishizuka, K., Horita, S., Kajiho, Y., Miura, K., Igarashi, T., Hattori, M., Kitanaka, S.
|
|
<strong>LMX1B mutation with residual transcriptional activity as a cause of isolated glomerulopathy.</strong>
|
|
Nephrol. Dial. Transplant. 29: 81-88, 2014.
|
|
|
|
|
|
[PubMed: 24042019]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/ndt/gft359]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johnson, R. L., Tabin, C. J.
|
|
<strong>Molecular models for vertebrate limb development.</strong>
|
|
Cell 90: 979-990, 1997.
|
|
|
|
|
|
[PubMed: 9323126]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)80364-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kania, A., Johnson, R. L., Jessell, T. M.
|
|
<strong>Coordinate roles for LIM homeobox genes in directing the dorsoventral trajectory of motor axons in the vertebrate limb.</strong>
|
|
Cell 102: 161-173, 2000.
|
|
|
|
|
|
[PubMed: 10943837]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)00022-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lei, L., Oh, G., Sutherland, S., Abra, G., Higgins, J., Sibley, R., Troxell, M., Kambham, N.
|
|
<strong>Myelin bodies in LMX1B-associated nephropathy: potential for misdiagnosis.</strong>
|
|
Pediat. Nephrol. 35: 1647-1657, 2020.
|
|
|
|
|
|
[PubMed: 32356190]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00467-020-04564-w]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lichter, P. R., Richards, J. E., Downs, C. A., Stringham, H. M., Boehnke, M., Farley, F. A.
|
|
<strong>Cosegregation of open-angle glaucoma and the nail-patella syndrome.</strong>
|
|
Am. J. Ophthal. 124: 506-515, 1997.
|
|
|
|
|
|
[PubMed: 9323941]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0002-9394(14)70866-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Marini, M., Giacopelli, F., Seri, M., Ravazzolo, R.
|
|
<strong>Interaction of the LMX1B and PAX2 gene products suggests possible molecular basis of differential phenotypes in nail-patella syndrome.</strong>
|
|
Europ. J. Hum. Genet. 13: 789-792, 2005.
|
|
|
|
|
|
[PubMed: 15785774]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5201405]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McIntosh, I., Dreyer, S. D., Clough, M. V., Dunston, J. A., Eyaid, W., Roig, C. M., Montgomery, T., Ala-Mello, S., Kaitila, I., Winterpacht, A., Zabel, B., Frydman, M., Cole, W. G., Francomano, C. A., Lee, B.
|
|
<strong>Mutation analysis of LMX1B gene in nail-patella syndrome patients.</strong>
|
|
Am. J. Hum. Genet. 63: 1651-1658, 1998.
|
|
|
|
|
|
[PubMed: 9837817]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302165]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Morello, R., Zhou, G., Dreyer, S. D., Harvey, S. J., Ninomiya, Y., Thorner, P. S., Miner, J. H., Cole, W., Winterpacht, A., Zabel, B., Oberg, K. C., Lee, B.
|
|
<strong>Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome.</strong>
|
|
Nature Genet. 27: 205-208, 2001.
|
|
|
|
|
|
[PubMed: 11175791]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/84853]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pilz, A., Prohaska, R., Peters, J., Abbott, C.
|
|
<strong>Genetic linkage analysis of the Ak1, Col5a1, Epb7.2, Fpgs, Grp78, Pbx3, and Notch1 genes in the region of mouse chromosome 2 homologous to human chromosome 9q.</strong>
|
|
Genomics 21: 104-109, 1994.
|
|
|
|
|
|
[PubMed: 8088777]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1994.1230]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pinto e Vairo, F., Pichurin, P. N., Fervenza, F. C., Nasr, S. H., Mills, K., Schmitz, C. T., Klee, E. W., Herrmann, S. M.
|
|
<strong>Nail-patella-like renal disease masquerading as Fabry disease on kidney biopsy: a case report.</strong>
|
|
BMC Nephrol. 21: 341, 2020. Note: Electronic Article.
|
|
|
|
|
|
[PubMed: 32791958]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1186/s12882-020-02012-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vogel, A., Rodriguez, C., Warnken, W., Izpisua Belmonte, J. C.
|
|
<strong>Dorsal cell fate specified by chick Lmx1 during vertebrate limb development.</strong>
|
|
Nature 378: 716-720, 1995. Note: Erratum: Nature 379: 848 only, 1996.
|
|
|
|
|
|
[PubMed: 7501017]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/378716a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vollrath, D., Jaramillo-Babb, V. L., Clough, M. V., McIntosh, I., Scott, K. M., Lichter, P. R., Richards, J. E.
|
|
<strong>Loss-of-function mutations in the LIM-homeodomain gene, LMX1B, in nail-patella syndrome.</strong>
|
|
Hum. Molec. Genet. 7: 1091-1098, 1998. Erratum: Hum. Molec. Genet. 7: 1333 only, 1998.
|
|
|
|
|
|
[PubMed: 9618165]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/7.7.1091]
|
|
|
|
|
|
</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">
|
|
Bao Lige - updated : 03/11/2022<br>Cassandra L. Kniffin - updated : 11/24/2020<br>Cassandra L. Kniffin - updated : 2/25/2009<br>Marla J. F. O'Neill - updated : 2/14/2006<br>Cassandra L. Kniffin - updated : 6/16/2005<br>Patricia A. Hartz - updated : 8/26/2004<br>Cassandra L. Kniffin - updated : 8/15/2003<br>Patricia A. Hartz - updated : 1/23/2003<br>Victor A. McKusick - updated : 1/25/2001<br>Victor A. McKusick - updated : 11/1/2000<br>Stylianos E. Antonarakis - updated : 8/4/2000<br>George E. Tiller - updated : 5/8/2000<br>Victor A. McKusick - updated : 12/11/1998<br>Sheryl A. Jankowski - updated : 8/11/1998<br>Victor A. McKusick - updated : 6/19/1998<br>Ada Hamosh - updated : 4/30/1998
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 4/27/1998
|
|
</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 : 07/25/2024<br>alopez : 02/08/2024<br>carol : 01/09/2024<br>carol : 09/21/2022<br>mgross : 03/11/2022<br>carol : 12/15/2020<br>carol : 12/11/2020<br>alopez : 12/07/2020<br>ckniffin : 11/24/2020<br>terry : 03/14/2013<br>terry : 10/4/2012<br>wwang : 3/19/2009<br>ckniffin : 2/25/2009<br>alopez : 7/5/2007<br>wwang : 2/16/2006<br>terry : 2/14/2006<br>wwang : 7/7/2005<br>ckniffin : 6/16/2005<br>terry : 4/5/2005<br>mgross : 8/30/2004<br>mgross : 8/30/2004<br>terry : 8/26/2004<br>terry : 3/18/2004<br>alopez : 9/2/2003<br>carol : 8/18/2003<br>ckniffin : 8/15/2003<br>mgross : 1/23/2003<br>carol : 2/13/2002<br>alopez : 1/29/2001<br>terry : 1/25/2001<br>mcapotos : 11/8/2000<br>mcapotos : 11/3/2000<br>terry : 11/1/2000<br>mgross : 8/4/2000<br>alopez : 5/8/2000<br>mcapotos : 1/4/2000<br>jlewis : 6/24/1999<br>carol : 12/15/1998<br>terry : 12/11/1998<br>carol : 8/11/1998<br>carol : 6/22/1998<br>terry : 6/19/1998<br>alopez : 4/30/1998<br>alopez : 4/27/1998
|
|
</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>
|
|
|
|
|