4081 lines
338 KiB
Text
4081 lines
338 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
|
|
|
|
- *150340 - LAMIN B1; LMNB1
|
|
|
|
|
|
- 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=150340"><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 class="hidden-sm hidden-xs">
|
|
|
|
|
|
Display:
|
|
|
|
|
|
<label style="font-weight: normal"><input type="checkbox" id="mimToggleChangeBars" checked /> Change Bars </label>
|
|
|
|
|
|
</span>
|
|
|
|
|
|
</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">*150340</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="#cytogenetics">Cytogenetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/150340">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=ENSG00000113368;t=ENST00000261366" 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=4001" 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=150340" 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=ENSG00000113368;t=ENST00000261366" 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_001198557,NM_005573,NR_134488,NR_177109,XM_047417173,XM_047417174,XM_047417175" 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_005573" 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=150340" 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=01036&isoform_id=01036_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/LMNB1" 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/125953,307106,576840,5031877,15126742,50415798,74354337,119569230,119569231,189069155,194381652,310689049,2217355800,2217355802,2217355804,2462602489,2462602491" 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/P20700" 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=4001" 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=ENSG00000113368;t=ENST00000261366" 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=LMNB1" 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=LMNB1" 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+4001" 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/LMNB1" 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:4001" 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/4001" 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=chr5&hgg_gene=ENST00000261366.10&hgg_start=126776623&hgg_end=126837020&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:6637" 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://medlineplus.gov/genetics/gene/lmnb1" 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=150340[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=150340[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.deciphergenomics.org/gene/LMNB1/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000113368" 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=LMNB1" 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=LMNB1" 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=LMNB1" 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=LMNB1&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/PA30403" 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:6637" 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/FBgn0002525.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:96795" 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/LMNB1#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:96795" 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/4001/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=4001" 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=WBGene00003052;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-020424-2" 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://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:4001" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://reactome.org/content/query?q=LMNB1&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> 448054001<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>
|
|
150340
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
LAMIN B1; LMNB1
|
|
|
|
</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">
|
|
LMNB
|
|
</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=LMNB1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">LMNB1</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/5/408?start=-3&limit=10&highlight=408">5q23.2</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr5:126776623-126837020&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'})">5:126,776,623-126,837,020</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=621061,169500,619179" 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="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/5/408?start=-3&limit=10&highlight=408">
|
|
5q23.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Leukodystrophy, demyelinating, adult-onset, autosomal dominant, atypical
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/621061"> 621061 </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">
|
|
Leukodystrophy, demyelinating, adult-onset, autosomal dominant, typical
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/169500"> 169500 </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">
|
|
Microcephaly 26, primary, autosomal dominant
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/619179"> 619179 </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/150340" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/150340" 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>Lamins are the major components of the nuclear lamina which underlies the nuclear envelope of eukaryotic cells (see lamin A, <a href="/entry/150330">150330</a>). <a href="#15" class="mim-tip-reference" title="Maeno, H., Sugimoto, K., Nakajima, N. <strong>Genomic structure of the mouse gene (Lmnb1) encoding nuclear lamin B1.</strong> Genomics 30: 342-346, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8586436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8586436</a>] [<a href="https://doi.org/10.1006/geno.1995.9868" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8586436">Maeno et al. (1995)</a> noted that lamins are members of the intermediate filament protein family. Vertebrate lamins are classified into 2 types, A and B, and mammalian somatic cells show 2 species of each type: lamins A and C for the A type and B1 and B2 for the B type. In addition, germ-cell-specific lamins have been reported for both types (<a href="#8" class="mim-tip-reference" title="Furukawa, K., Hotta, Y. <strong>cDNA cloning of a germ cell specific lamin B3 from mouse spermatocytes and analysis of its function by ectopic expression in somatic cells.</strong> EMBO J. 12: 97-106, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8094052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8094052</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1993.tb05635.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8094052">Furukawa and Hotta, 1993</a> and <a href="#9" class="mim-tip-reference" title="Furukawa, K., Inagaki, H., Hotta, Y. <strong>Identification and cloning of an mRNA coding for a germ cell-specific A-type lamin in mice.</strong> Exp. Cell Res. 212: 426-430, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8187835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8187835</a>] [<a href="https://doi.org/10.1006/excr.1994.1164" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8187835">Furukawa et al., 1994</a>). Whereas A-type lamins are expressed in a developmentally controlled manner, B-type lamins are expressed in all kinds of cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8094052+8187835+8586436" 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><a href="#19" class="mim-tip-reference" title="Pollard, K. M., Chan, E. K., Grant, B. J., Sullivan, K. E., Tan, E. M., Glass, C. A. <strong>In vitro posttranslational modification of lamin B clones from a human T-cell line.</strong> Molec. Cell. Biol. 10: 2164-2175, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2325650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2325650</a>] [<a href="https://doi.org/10.1128/mcb.10.5.2164-2175.1990" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2325650">Pollard et al. (1990)</a> cloned a lamin B cDNA from the human T-cell line MOLT-4. LMNB1 encodes a deduced 586-amino acid protein with a calculated molecular mass of 66,334 Da. The LMNB1 protein shares approximately 72% sequence similarity with lamin A/C (<a href="/entry/150330">150330</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2325650" 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>Lamin B, a component of the interphase nuclear lamina, is required to maintain nuclear shape and mechanical integrity (<a href="#11" class="mim-tip-reference" title="Goldman, R. D., Gruenbaum, Y., Moir, R. D., Shumaker, D. K., Spann, T. P. <strong>Nuclear lamins: building blocks of nuclear architecture.</strong> Genes Dev. 16: 533-547, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11877373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11877373</a>] [<a href="https://doi.org/10.1101/gad.960502" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11877373">Goldman et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11877373" 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="Tsai, M.-Y., Wang, S., Heidinger, J. M., Shumaker, D. K., Adam, S. A., Goldman, R. D., Zheng, Y. <strong>A mitotic lamin B matrix induced by RanGTP required for spindle assembly.</strong> Science 311: 1887-1893, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16543417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16543417</a>] [<a href="https://doi.org/10.1126/science.1122771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16543417">Tsai et al. (2006)</a> reported that lamin B has a role in spindle assembly. Lamin B assembled into a matrix-like network in mitosis through a process that depended on the presence of the GTP-bound form of the small guanosine triphosphatase (GTPase) Ran (<a href="/entry/601179">601179</a>). Depletion of lamin B resulted in defects in spindle assembly. Dominant-negative mutant lamin B proteins that disrupt lamin B assembly in interphase nuclei also disrupted spindle assembly in mitosis. Furthermore, lamin B was essential for the formation of the mitotic matrix that tethers a number of spindle assembly factors. <a href="#21" class="mim-tip-reference" title="Tsai, M.-Y., Wang, S., Heidinger, J. M., Shumaker, D. K., Adam, S. A., Goldman, R. D., Zheng, Y. <strong>A mitotic lamin B matrix induced by RanGTP required for spindle assembly.</strong> Science 311: 1887-1893, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16543417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16543417</a>] [<a href="https://doi.org/10.1126/science.1122771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16543417">Tsai et al. (2006)</a> proposed that lamin B is a structural component of the long-sought-after spindle matrix that promotes microtubule assembly and organization in mitosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16543417" 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="Kim, Y., Sharov, A. A., McDole, K., Cheng, M., Hao, H., Fan, C.-M., Gaiano, N., Ko, M. S. H., Zheng, Y. <strong>Mouse B-type lamins are required for proper organogenesis but not by embryonic stem cells.</strong> Science 334: 1706-1710, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22116031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22116031</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22116031[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1211222" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22116031">Kim et al. (2011)</a> found that mouse embryonic stem cells do not need any lamins for self-renewal and pluripotency. Although genomewide lamin-B binding profiles correlate with reduced gene expression, such binding is not directly required for gene silencing in embryonic stem cells or trophectoderm cells. However, B-type lamins are required for proper organogenesis. Defects in spindle orientation in neural progenitor cells and migration of neurons probably cause brain disorganizations found in lamin-B-null mice. <a href="#13" class="mim-tip-reference" title="Kim, Y., Sharov, A. A., McDole, K., Cheng, M., Hao, H., Fan, C.-M., Gaiano, N., Ko, M. S. H., Zheng, Y. <strong>Mouse B-type lamins are required for proper organogenesis but not by embryonic stem cells.</strong> Science 334: 1706-1710, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22116031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22116031</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22116031[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1211222" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22116031">Kim et al. (2011)</a> concluded that their studies not only disprove several prevailing views of lamin-Bs but also establish a foundation for redefining the function of the nuclear lamina in the context of tissue building and homeostasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22116031" 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="Dou, Z., Xu, C., Donahue, G., Shimi, T., Pan, J.-A., Zhu, J., Ivanov, A., Capell, B. C., Drake, A. M., Shah, P. P., Catanzaro, J. M., Ricketts, M. D., Lamark, T., Adam, S. A., Marmorstein, R., Zong, W.-X., Johansen, T., Goldman, R. D., Adams, P. D., Berger, S. L. <strong>Autophagy mediates degradation of nuclear lamina.</strong> Nature 527: 105-109, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26524528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26524528</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26524528[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/nature15548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26524528">Dou et al. (2015)</a> reported that the autophagy machinery mediates degradation of nuclear lamina components in mammals. The autophagy protein LC3/Atg8 (<a href="/entry/601242">601242</a>), which is involved in autophagy membrane trafficking and substrate delivery, is present in the nucleus and directly interacts with the nuclear lamina protein lamin B1, and binds to lamin-associated domains on chromatin. This LC3-lamin B1 interaction does not downregulate lamin B1 during starvation, but mediates its degradation upon oncogenic insults, such as by activated RAS (see <a href="/entry/190020">190020</a>). Lamin B1 degradation is achieved by nucleus-to-cytoplasm transport that delivers lamin B1 to the lysosome. Inhibiting autophagy or the LC3-lamin B1 interaction prevented activated RAS-induced lamin B1 loss and attenuated oncogene-induced senescence in primary human cells. <a href="#6" class="mim-tip-reference" title="Dou, Z., Xu, C., Donahue, G., Shimi, T., Pan, J.-A., Zhu, J., Ivanov, A., Capell, B. C., Drake, A. M., Shah, P. P., Catanzaro, J. M., Ricketts, M. D., Lamark, T., Adam, S. A., Marmorstein, R., Zong, W.-X., Johansen, T., Goldman, R. D., Adams, P. D., Berger, S. L. <strong>Autophagy mediates degradation of nuclear lamina.</strong> Nature 527: 105-109, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26524528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26524528</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26524528[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/nature15548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26524528">Dou et al. (2015)</a> concluded that this function of autophagy acts as a guarding mechanism protecting cells from tumorigenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26524528" 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="#14" class="mim-tip-reference" title="Lin, F., Worman, H. J. <strong>Structural organization of the human gene (LMNB1) encoding nuclear lamin B1.</strong> Genomics 27: 230-236, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7557986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7557986</a>] [<a href="https://doi.org/10.1006/geno.1995.1036" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7557986">Lin and Worman (1995)</a> determined that the human LMNB1 gene contains 11 exons. The transcription unit spans more than 45 kb and the transcription start site is 348 nucleotides upstream from the translation initiation codon. Exon 1 codes for the N-terminal head domain and the first portion of the central rod domain, exons 2 through 6 the central rod domain, and exons 7 through 11 the C-terminal tail domain. Intron positions are conserved in other lamin genes from frogs, mice, and humans but different in lamin genes from Drosophila and C. elegans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7557986" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Maeno, H., Sugimoto, K., Nakajima, N. <strong>Genomic structure of the mouse gene (Lmnb1) encoding nuclear lamin B1.</strong> Genomics 30: 342-346, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8586436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8586436</a>] [<a href="https://doi.org/10.1006/geno.1995.9868" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8586436">Maeno et al. (1995)</a> demonstrated that the mouse lamin B1 gene spans about 43 kb of the genome and contains 11 exons, Exon/intron structure of the B1 gene clearly showed the conserved organization among the intermediate filament protein family genes. The presumptive promoter region has high GC content and contains a CAAT box and multiple Sp1 sites but no classical TATA box, suggesting to the authors that the lamin B1 gene has a typical housekeeping gene promoter with a CpG island. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8586436" 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>The lamin B gene in the mouse is located on chromosome 18 (<a href="#12" class="mim-tip-reference" title="Justice, M. J., Gilbert, D. J., Kinzler, K. W., Vogelstein, B., Buchberg, A. M., Ceci, J. D., Matsuda, Y., Chapman, V. M., Patriotis, C., Makris, A., Tsichlis, P. N., Jenkins, N. A., Copeland, N. G. <strong>A molecular genetic linkage map of mouse chromosome 18 reveals extensive linkage conservation with human chromosomes 5 and 18.</strong> Genomics 13: 1281-1288, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1354644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1354644</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90047-v" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1354644">Justice et al., 1992</a>) in a region of linkage homology to the long arm of human chromosome 5. <a href="#23" class="mim-tip-reference" title="Wydner, K. L., McNeil, J. A., Lin, F., Worman, H. J., Lawrence, J. B. <strong>Chromosomal assignment of human nuclear envelope protein genes LMNA, LMNB1, and LBR by fluorescence in situ hybridization.</strong> Genomics 32: 474-478, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8838815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8838815</a>] [<a href="https://doi.org/10.1006/geno.1996.0146" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8838815">Wydner et al. (1996)</a> mapped the human LMNB1 gene to 5q23.3-q31.1 by fluorescence in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1354644+8838815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cytogenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimCytogeneticsFold" id="mimCytogeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCytogeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cytogenetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCytogeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p><strong><em>Typical Autosomal Dominant Adult-Onset Demyelinating Leukodystrophy</em></strong></p><p>
|
|
In affected members of a 4 unrelated families, including the large multigenerational Irish family from New Jersey (family K2685) originally reported by <a href="#7" class="mim-tip-reference" title="Eldridge, R., Anayiotos, C. P., Schlesinger, S., Cowen, D., Bever, C., Patronas, N., McFarland, H. <strong>Hereditary adult-onset leukodystrophy simulating chronic progressive multiple sclerosis.</strong> New Eng. J. Med. 311: 948-953, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6472420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6472420</a>] [<a href="https://doi.org/10.1056/NEJM198410113111504" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6472420">Eldridge et al. (1984)</a>, with typical autosomal dominant adult-onset demyelinating leukodystrophy (ADLDTY; <a href="/entry/169500">169500</a>) <a href="#16" class="mim-tip-reference" title="Padiath, Q. S., Saigoh, K., Schiffmann, R., Asahara, H., Yamada, T., Koeppen, A., Hogan, K., Ptacek, L. J., Fu, Y.-H. <strong>Lamin B1 duplications cause autosomal dominant leukodystrophy.</strong> Nature Genet. 38: 1114-1123, 2006. Note: Erratum: Nature Genet. 39: 276 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16951681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16951681</a>] [<a href="https://doi.org/10.1038/ng1872" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16951681">Padiath et al. (2006)</a> identified a heterozygous tandem genomic duplication on chromosome 5q23 resulting in an extra copy of the LMNB1 gene. The duplication was identified by sequencing genomic DNA from affected individuals and also from mouse-human hybrid cell lines derived from cells of affected individuals. The duplications segregated with the disorder in the families. The hybrid cell lines enabled <a href="#16" class="mim-tip-reference" title="Padiath, Q. S., Saigoh, K., Schiffmann, R., Asahara, H., Yamada, T., Koeppen, A., Hogan, K., Ptacek, L. J., Fu, Y.-H. <strong>Lamin B1 duplications cause autosomal dominant leukodystrophy.</strong> Nature Genet. 38: 1114-1123, 2006. Note: Erratum: Nature Genet. 39: 276 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16951681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16951681</a>] [<a href="https://doi.org/10.1038/ng1872" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16951681">Padiath et al. (2006)</a> to separate chromosomes derived from each of the 2 parents of an individual and to assign phase unambiguously when identifying sequencing variants. They constructed a haplotype map of the chromosome carrying the disease-causing mutation and observed a large shared haplotype block in the critical region in 2 families, suggesting a common founder. The other 2 families each carried unique duplications. Increased expression of lamin B1 in Drosophila melanogaster resulted in a degenerative phenotype. In addition, an abnormal nuclear morphology was apparent when cultured cells overexpressed this protein. Antibodies to lamin B are found in individuals with autoimmune diseases, and it is also an antigen recognized by a monoclonal antibody raised against plaques from brains of individuals with multiple sclerosis (<a href="/entry/126200">126200</a>). This raised the possibility that lamin B may be a link to the autoimmune attack that occurs in multiple sclerosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16951681+6472420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Brussino, A., Vaula, G., Cagnoli, C., Mauro, A., Pradotto, L., Daniele, D., Di Gregorio, E., Barberis, M., Arduino, C., Squadrone, S., Abete, M. C., Migone, N., Calabrese, O., Brusco, A. <strong>A novel family with lamin B1 duplication associated with adult-onset leucoencephalopathy.</strong> J. Neurol. Neurosurg. Psychiat. 80: 237-240, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19151023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19151023</a>] [<a href="https://doi.org/10.1136/jnnp.2008.147330" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19151023">Brussino et al. (2009)</a> found a 140- to 190-kb duplication of 5q including the entire LMNB1 gene, the AX748201 transcript, and the 3-prime end of the MARCH3 gene (<a href="/entry/613333">613333</a>) in 1 of 8 Italian probands with adult-onset leukoencephalopathy. The patient's affected cousin also carried the duplication, and there was a family history of a similar disorder. Lamin B1 expression was increased in lymphoblasts from one of the patients with the duplication. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19151023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 4 unrelated families with typical ADLD, <a href="#20" class="mim-tip-reference" title="Schuster, J., Sundblom, J., Thuresson, A.-C., Hassin-Baer, S., Klopstock, T., Dichgans, M., Cohen, O. S., Raininko, R., Melberg, A., Dahl, N. <strong>Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms.</strong> Neurogenetics 12: 65-72, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21225301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21225301</a>] [<a href="https://doi.org/10.1007/s10048-010-0269-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21225301">Schuster et al. (2011)</a> found heterozygous duplications involving the LMNB1 gene. All 4 duplications were of different sizes, ranging from 107 to 218 kb, supporting independent events. Five patients from 2 families had about a 2-fold increased level of LMNB1 protein in white blood cells, and LMNB1 mRNA was also increased compared to controls. Each duplication extended over part of the MARCH3 gene, but MARCH3 mRNA was not increased in patient leukocytes. <a href="#20" class="mim-tip-reference" title="Schuster, J., Sundblom, J., Thuresson, A.-C., Hassin-Baer, S., Klopstock, T., Dichgans, M., Cohen, O. S., Raininko, R., Melberg, A., Dahl, N. <strong>Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms.</strong> Neurogenetics 12: 65-72, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21225301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21225301</a>] [<a href="https://doi.org/10.1007/s10048-010-0269-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21225301">Schuster et al. (2011)</a> concluded that an accurate molecular diagnosis of the disorder could be made by direct analysis of LMNB1 in peripheral leukocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21225301" 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 symptomatic man with ADLD and his asymptomatic sister who had leukodystrophy on brain imaging, <a href="#5" class="mim-tip-reference" title="Dos Santos, M. M., Grond-Ginsbach, C., Aksay, S. S., Chen, B., Tchatchou, S., Wolf, N. I., van der Knaap, M. S., Grau, A. J. <strong>Adult-onset autosomal dominant leukodystrophy due to LMNB1 gene duplication. (Letter)</strong> J. Neurol. 259: 579-581, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21909802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21909802</a>] [<a href="https://doi.org/10.1007/s00415-011-6225-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21909802">Dos Santos et al. (2012)</a> identified a heterozygous 148-kb duplication on chromosome 5q23.2 including the LMNB1 gene, but not the MARCH3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21909802" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using a custom array, <a href="#10" class="mim-tip-reference" title="Giorgio, E., Rolyan, H., Kropp, L., Chakka, A. B., Yatsenko, S., Di Gregorio, E., Lacerenza, D., Vaula, G., Talarico, F., Mandich, P., Toro, C., Pierre, E. E., and 26 others. <strong>Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression.</strong> Hum. Mutat. 34: 1160-1171, 2013. Note: Erratum: Hum. Mutat. 35: 149 only, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23649844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23649844</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23649844[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.22348" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23649844">Giorgio et al. (2013)</a> performed detailed breakpoint junction sequence analysis of the duplicated 5q23 region containing the LMNB1 gene in 20 independent families with ADLD in whom genomic LMNB1 duplication was initially identified by aCGH, QT-PCR, or MLPA. Seven families had previously been reported (<a href="#2" class="mim-tip-reference" title="Brussino, A., Vaula, G., Cagnoli, C., Mauro, A., Pradotto, L., Daniele, D., Di Gregorio, E., Barberis, M., Arduino, C., Squadrone, S., Abete, M. C., Migone, N., Calabrese, O., Brusco, A. <strong>A novel family with lamin B1 duplication associated with adult-onset leucoencephalopathy.</strong> J. Neurol. Neurosurg. Psychiat. 80: 237-240, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19151023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19151023</a>] [<a href="https://doi.org/10.1136/jnnp.2008.147330" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19151023">Brussino et al., 2009</a>; <a href="#20" class="mim-tip-reference" title="Schuster, J., Sundblom, J., Thuresson, A.-C., Hassin-Baer, S., Klopstock, T., Dichgans, M., Cohen, O. S., Raininko, R., Melberg, A., Dahl, N. <strong>Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms.</strong> Neurogenetics 12: 65-72, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21225301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21225301</a>] [<a href="https://doi.org/10.1007/s10048-010-0269-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21225301">Schuster et al., 2011</a>; <a href="#5" class="mim-tip-reference" title="Dos Santos, M. M., Grond-Ginsbach, C., Aksay, S. S., Chen, B., Tchatchou, S., Wolf, N. I., van der Knaap, M. S., Grau, A. J. <strong>Adult-onset autosomal dominant leukodystrophy due to LMNB1 gene duplication. (Letter)</strong> J. Neurol. 259: 579-581, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21909802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21909802</a>] [<a href="https://doi.org/10.1007/s00415-011-6225-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21909802">Dos Santos et al., 2012</a>). There were a total of 16 unique heterozygous rearrangements. Three of the duplications were shared by more than 1 family: 1 was found in 3 families and the other 2 duplications were found in 2 families each. Individuals with identical junctions shared the same haplotype, consistent with a founder effect. Duplication sizes ranged from about 128 kb to 475 kb. The largest duplication also included the PHAX (<a href="/entry/604924">604924</a>), ALDH7A1 (<a href="/entry/107323">107323</a>), and GRAMD3 (GRAMD2B; <a href="/entry/620182">620182</a>) genes. Comparison of all the samples identified a 72-kb minimal critical duplicated region required for ADLD that contained only the LMNB1 gene. All but 1 of the duplications were in the direct tandem orientation; the remaining duplication was inverted (see ADLDAT, <a href="/entry/621061">621061</a>). Characterization of the junction sequences showed that most (11 of 15) showed short stretches of microhomology overlap ranging from 1 to 6 nucleotides, whereas the others showed small insertions at the breakpoints. All duplications resulted from intrachromosomal rearrangements. Analysis of the genomic architecture suggested several potential mechanisms for the duplications, including nonhomologous end joining (NHEJ) or fork stalling and template switching/microhomology-mediated break-induced repair (FoSTeS/MMBIR). The enrichment of Alu repetitive elements at the centromeric breakpoints (found in 4 cases), higher GC content, and high frequency of repetitive sequences at breakpoints likely also played a role in mediating ADLD duplications. RT-PCR of patients fibroblasts or blood showed increased LMNB1 expression (2.1- to 4.8-fold compared to controls), as well as increased protein levels (1.6- to 3.2-fold compared to controls). There was no apparent difference in phenotype according to duplication size. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19151023+23649844+21225301+21909802" 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 high-throughput chromosome conformation capture (Hi-C) techniques to analyze topologically associating domains (TADs), <a href="#4" class="mim-tip-reference" title="Dimartino, P., Zadorozhna, M., Yumiceba, V., Basile, A., Cani, I., Melo, U. S., Henck, J., Breur, M., Tonon, C., Lodi, R., Brusco, A., Pippucci, T., and 12 others. <strong>Structural variants at the LMNB1 locus: deciphering pathomechanisms in autosomal dominant adult-onset demyelinating leukodystrophy.</strong> Ann. Neurol. 96: 855-870, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/39078102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">39078102</a>] [<a href="https://doi.org/10.1002/ana.27038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="39078102">Dimartino et al. (2024)</a> found that patients with typical ADLD (<a href="#10" class="mim-tip-reference" title="Giorgio, E., Rolyan, H., Kropp, L., Chakka, A. B., Yatsenko, S., Di Gregorio, E., Lacerenza, D., Vaula, G., Talarico, F., Mandich, P., Toro, C., Pierre, E. E., and 26 others. <strong>Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression.</strong> Hum. Mutat. 34: 1160-1171, 2013. Note: Erratum: Hum. Mutat. 35: 149 only, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23649844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23649844</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23649844[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.22348" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23649844">Giorgio et al., 2013</a>; <a href="#1" class="mim-tip-reference" title="Brunetti, V., Ferilli, M. A., Nociti, V., Silvestri, G. <strong>Teaching NeuroImages: autosomal dominant leukodystrophy in a sporadic case.</strong> Neurology 83: e121, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25224534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25224534</a>] [<a href="https://doi.org/10.1212/WNL.0000000000000803" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25224534">Brunetti et al., 2014</a>) carried intra-TAD duplications on 5q23 within the LMNB1 TAD that did not extend beyond TAD boundaries and maintained the physiologic regulatory context of LMNB1. This resulted in overexpression of the LMNB1 gene. The authors concluded that duplication of the LMNB1 gene per se is not causative of typical ADLD, which will affect ADLD diagnosis and genetic counseling. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=39078102+23649844+25224534" 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>See also atypical autosomal dominant adult-onset demyelinating leukodystrophy (ADLDAT; <a href="/entry/621061">621061</a>), which is caused by heterozygous deletions of chromosome 5q23 involving regulatory regions upstream of the LMNB1 gene.</p></div>
|
|
</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>Autosomal Dominant Primary Microcephaly 26</em></strong>
|
|
</p>
|
|
|
|
<p>In 7 patients from 5 unrelated families with autosomal dominant primary microcephaly-26 (MCPH26; <a href="/entry/619179">619179</a>), <a href="#3" class="mim-tip-reference" title="Cristofoli, F., Moss, T., Moore, H. W., Devriendt, K., Flanagan-Steet, H., May, M., Jones, J., Roelens, F., Fons, C., Fernandez, A., Martorell, L., Selicorni, A., Maitz, S., Vitiello, G., Van der Hoeven, G., Skinner, S. A., Bollen, M., Vermeesch, J. R., Steet, R., Van Esch, H. <strong>De novo variants in LMNB1 cause pronounced syndromic microcephaly and disruption of nuclear envelope integrity.</strong> Am. J. Hum. Genet. 107: 753-762, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32910914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32910914</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32910914[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2020.08.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32910914">Cristofoli et al. (2020)</a> identified heterozygous mutations in the LMNB1 gene (<a href="#0002">150340.0002</a>-<a href="#0006">150340.0006</a>). The mutations were found by whole-exome sequencing or microarray analysis and confirmed by Sanger sequencing. The mutations occurred de novo in 3 patients, whereas 1 was inherited from a mildly affected mother, and in 3 sibs were inherited from an unaffected father who was mosaic for the mutation. There was 1 intragenic deletion, 1 splice site mutation, and 3 missense variants affecting highly conserved residues. In vitro functional expression studies of the 3 missense variants showed that they caused variable abnormalities of the nuclear lamina and misshapen nuclei. One was associated with decreased protein expression, and the others caused mislocalization of LMNB1 to the cytoplasm. However, mitotic spindle formation and mitotic segregation did not appear to be affected. The authors postulated a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32910914" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
|
|
<p>In 7 unrelated patients (P1-P3, P9-P11, P13) with MCPH26, <a href="#17" class="mim-tip-reference" title="Parry, D. A., Martin, C.-A., Greene, P., Marsh, J. A., Genomics England Research Consortium, Blyth, M., Cox, H., Donnelly, D., Greenhalgh, L., Greville-Heygate, S., Harrison, V., Lachlan, K., McKenna, C., Quigley, A. J., Rea, G., Robertson, L., Suri, M., Jackson, A. P. <strong>Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy.</strong> Genet. Med. 23: 408-414, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33033404/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33033404</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33033404[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/s41436-020-00980-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33033404">Parry et al. (2021)</a> identified heterozygous mutations in the LMNB1 gene (see, e.g., <a href="#0004">150340.0004</a> and <a href="#0007">150340.0007</a>). There were 2 recurrent missense mutations and an in-frame deletion; none were present in the gnomAD database. The mutations occurred de novo in all patients for whom parental material was available. The location of the mutations predicted interference with dimer or filament assembly, and in vitro functional expression studies in cells transfected with the mutations showed that they caused abnormal LMNB1 nuclear aggregates and an altered nuclear shape. <a href="#17" class="mim-tip-reference" title="Parry, D. A., Martin, C.-A., Greene, P., Marsh, J. A., Genomics England Research Consortium, Blyth, M., Cox, H., Donnelly, D., Greenhalgh, L., Greville-Heygate, S., Harrison, V., Lachlan, K., McKenna, C., Quigley, A. J., Rea, G., Robertson, L., Suri, M., Jackson, A. P. <strong>Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy.</strong> Genet. Med. 23: 408-414, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33033404/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33033404</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33033404[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/s41436-020-00980-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33033404">Parry et al. (2021)</a> postulated that the mutations may alter the properties of lamin filaments, resulting in fragile nuclei that are susceptible to the mechanical stresses of nuclear and neuronal migration, leading to increased cell death during brain development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33033404" 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>
|
|
|
|
<div class="mim-changed mim-change"><p><strong><em>Associations Pending Confirmation</em></strong>
|
|
</p></div>
|
|
|
|
<div class="mim-changed mim-change"><p>In a 42-year-old woman of Italian ancestry, who was born in Brazil, with clinical features of ADLD, <a href="#18" class="mim-tip-reference" title="Pedroso, J. L., Munford, V., Bastos, A. U., Castro, L. P., Marussi, V. H. R., Silva, G. S., Arita, J. H., Menck, C. F. M., Barsottini, O. G. <strong>LMNB1 mutation causes cerebellar involvement and a genome instability defect.</strong> J. Neurol. Sci. 379: 249-252, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28716252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28716252</a>] [<a href="https://doi.org/10.1016/j.jns.2017.06.027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28716252">Pedroso et al. (2017)</a> identified a heterozygous missense variant in the LMNB1 gene (R29W). The variant, which was found by whole-exome sequencing, was not present in several public databases, including the Exome Sequencing Project and ExAC. Patient-derived cells showed increased expression of variant LMNB1 mRNA, as well as nuclear structural abnormalities. Functional studies demonstrated an impaired response to DNA damage, suggesting genomic instability. The patient presented at 23 years of age with progressive cerebellar atrophy and cognitive impairment. Brain imaging showed white matter abnormalities in the cerebellum, as well as atrophy of the corpus callosum, brainstem, and spinal cord. In in vitro studies, <a href="#3" class="mim-tip-reference" title="Cristofoli, F., Moss, T., Moore, H. W., Devriendt, K., Flanagan-Steet, H., May, M., Jones, J., Roelens, F., Fons, C., Fernandez, A., Martorell, L., Selicorni, A., Maitz, S., Vitiello, G., Van der Hoeven, G., Skinner, S. A., Bollen, M., Vermeesch, J. R., Steet, R., Van Esch, H. <strong>De novo variants in LMNB1 cause pronounced syndromic microcephaly and disruption of nuclear envelope integrity.</strong> Am. J. Hum. Genet. 107: 753-762, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32910914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32910914</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32910914[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2020.08.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32910914">Cristofoli et al. (2020)</a> demonstrated that the R29W variant was present in the nuclear extract, suggesting that it did not disrupt nuclear lamina localization of LMNB1. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=28716252+32910914" 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></div>
|
|
</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>Mutations affecting A-type lamins have been associated with a variety of human diseases, including muscular dystrophy (e.g., <a href="/entry/181350">181350</a>), cardiomyopathy (e.g., <a href="/entry/115200">115200</a>), lipodystrophy (e.g., <a href="/entry/151660">151660</a>), and progeria (<a href="/entry/176670">176670</a>), but mutations in B-type lamins had not been identified in humans or in experimental animals. To investigate the in vivo function of lamin B1, <a href="#22" class="mim-tip-reference" title="Vergnes, L., Peterfy, M., Bergo, M. O., Young, S. G., Reue, K. <strong>Lamin B1 is required for mouse development and nuclear integrity.</strong> Proc. Nat. Acad. Sci. 101: 10428-10433, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15232008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15232008</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15232008[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0401424101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15232008">Vergnes et al. (2004)</a> generated mice with an insertional mutation in Lmnb1. The mutation resulted in the synthesis of a mutant lamin B1 protein lacking several key functional domains, including a portion of the rod domain, the nuclear localization signal, and the CAAX motif (the C-terminal signal for farnesylation). Homozygous Lmnb1 mutant mice survived embryonic development but died at birth with defects in lung and bone. Fibroblasts from mutant embryos grew under standard cell culture conditions but displayed grossly misshapen nuclei, impaired differentiation, increased polyploidy, and premature senescence. Thus, the lamin B1 mutant mice provided evidence for a broad and nonredundant function of lamin B1 in mammalian development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15232008" 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>7 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/150340" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=150340[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 MOVED TO <a href="#cytogenetics">CYTOGENETICS</a></strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0002" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 MICROCEPHALY 26, PRIMARY, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMNB1, ALA152GLY
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs935132421 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs935132421;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=rs935132421" 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=rs935132421" 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=RCV001254640 OR RCV001292576" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001254640, RCV001292576" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001254640...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 10-year-old boy (P1), born of unrelated Belgian parents, with autosomal dominant primary microcephaly-26 (MCPH26; <a href="/entry/619179">619179</a>), <a href="#3" class="mim-tip-reference" title="Cristofoli, F., Moss, T., Moore, H. W., Devriendt, K., Flanagan-Steet, H., May, M., Jones, J., Roelens, F., Fons, C., Fernandez, A., Martorell, L., Selicorni, A., Maitz, S., Vitiello, G., Van der Hoeven, G., Skinner, S. A., Bollen, M., Vermeesch, J. R., Steet, R., Van Esch, H. <strong>De novo variants in LMNB1 cause pronounced syndromic microcephaly and disruption of nuclear envelope integrity.</strong> Am. J. Hum. Genet. 107: 753-762, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32910914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32910914</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32910914[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2020.08.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32910914">Cristofoli et al. (2020)</a> identified a de novo heterozygous c.455C-G transversion (c.455C-G, NM_005573.3) in exon 2 of the LMNB1 gene, resulting in an ala152-to-gly (A152G) substitution at a highly conserved residue in the coil 1B domain. The mutation, which was found by trio-based whole-exome sequencing and confirmed by Sanger sequencing, was not present in public databases, including gnomAD. Patient cells showed decreased levels of the mutant protein. Transfection of the mutant protein into LMNB1-null HeLa cells also resulted in reduced protein levels, suggesting possible instability of the mutant protein, although further studies did not show increased turnover of the A152G protein compared to controls. The A152G variant caused abnormalities in the nuclear lamina, including abnormal and irregular ruffling, suggesting global disruption of the nuclear envelope. There was an increase in the percentage of cells with condensed nuclei, which may have been a result of overexpression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32910914" 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 MICROCEPHALY 26, PRIMARY, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMNB1, EX6-8 DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001254644 OR RCV002287475" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001254644, RCV002287475" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001254644...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 9-year-old Belgian girl (P2) with autosomal dominant primary microcephaly-26 (MCPH26; <a href="/entry/619179">619179</a>), <a href="#3" class="mim-tip-reference" title="Cristofoli, F., Moss, T., Moore, H. W., Devriendt, K., Flanagan-Steet, H., May, M., Jones, J., Roelens, F., Fons, C., Fernandez, A., Martorell, L., Selicorni, A., Maitz, S., Vitiello, G., Van der Hoeven, G., Skinner, S. A., Bollen, M., Vermeesch, J. R., Steet, R., Van Esch, H. <strong>De novo variants in LMNB1 cause pronounced syndromic microcephaly and disruption of nuclear envelope integrity.</strong> Am. J. Hum. Genet. 107: 753-762, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32910914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32910914</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32910914[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2020.08.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32910914">Cristofoli et al. (2020)</a> identified a heterozygous in-frame deletion in the LMNB1 gene, causing the deletion of exons 6-8 (Ser314_Thr497del). The deletion, which was found by microarray analysis, was inherited from the similarly affected mother in whom it occurred de novo. The deletion was predicted to result in a shortened protein lacking the nuclear localization signal. The authors postulated that the mutation results in insufficient protein abundance in the nucleus to form a stable laminar network and acts in a dominant-negative manner. However, functional studies of the variant and studies of patient cells were not performed. These patients had a milder phenotype than the others: the proband had a head circumference (HC) of -3.6 SD, whereas her mother had a HC of -2.5 SD and had learning difficulties. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32910914" 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 MICROCEPHALY 26, PRIMARY, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMNB1, LYS33GLU
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1750497172 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1750497172;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=rs1750497172" 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=rs1750497172" 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=RCV001254641 OR RCV001292578 OR RCV002558702" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001254641, RCV001292578, RCV002558702" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001254641...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old Italian girl (P3) with autosomal dominant primary microcephaly-26 (MCPH26; <a href="/entry/619179">619179</a>), <a href="#3" class="mim-tip-reference" title="Cristofoli, F., Moss, T., Moore, H. W., Devriendt, K., Flanagan-Steet, H., May, M., Jones, J., Roelens, F., Fons, C., Fernandez, A., Martorell, L., Selicorni, A., Maitz, S., Vitiello, G., Van der Hoeven, G., Skinner, S. A., Bollen, M., Vermeesch, J. R., Steet, R., Van Esch, H. <strong>De novo variants in LMNB1 cause pronounced syndromic microcephaly and disruption of nuclear envelope integrity.</strong> Am. J. Hum. Genet. 107: 753-762, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32910914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32910914</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32910914[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2020.08.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32910914">Cristofoli et al. (2020)</a> identified a de novo heterozygous c.97A-G transition (c.97A-G, NM_005573.3) in exon 1 of the LMNB1 gene, resulting in a lys33-to-glu (K33E) substitution at a highly conserved residue in the coil 1A domain near the head of the protein. The mutation, which was found by trio-based whole-exome sequencing and confirmed by Sanger sequencing, was not present in public databases, including gnomAD. Transfection of the mutant protein into LMNB1-null HeLa cells resulted in abnormal morphology of the nuclear lamina, which appeared diffuse, poorly formed, and with no discrete boundary. There was an increase in multilobed nuclei, which was also observed in patient-derived cells. Mutant LMNB1 was dispersed throughout the cell in the cytoplasm, indicating failure to incorporate into the laminar network; LMNB1 aggregates were often observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32910914" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 unrelated patients (P1, P9, and P11) with MCPH26, <a href="#17" class="mim-tip-reference" title="Parry, D. A., Martin, C.-A., Greene, P., Marsh, J. A., Genomics England Research Consortium, Blyth, M., Cox, H., Donnelly, D., Greenhalgh, L., Greville-Heygate, S., Harrison, V., Lachlan, K., McKenna, C., Quigley, A. J., Rea, G., Robertson, L., Suri, M., Jackson, A. P. <strong>Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy.</strong> Genet. Med. 23: 408-414, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33033404/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33033404</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33033404[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/s41436-020-00980-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33033404">Parry et al. (2021)</a> identified a de novo heterozygous K33E mutation in the LMNB1 gene. The location of the mutation was predicted to interfere with dimer or filament assembly, and in vitro functional expression studies in cells transfected with the mutant protein showed that it caused abnormal LMNB1 nuclear aggregates and an altered nuclear shape. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33033404" 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 MICROCEPHALY 26, PRIMARY, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMNB1, ARG42TRP
|
|
</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> rs1245844735 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1245844735;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/rs1245844735?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=rs1245844735" 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=rs1245844735" 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=RCV001254642 OR RCV001292579 OR RCV003148939" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001254642, RCV001292579, RCV003148939" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001254642...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-year-old girl (P4) with autosomal dominant primary microcephaly-26 (MCPH26; <a href="/entry/619179">619179</a>), <a href="#3" class="mim-tip-reference" title="Cristofoli, F., Moss, T., Moore, H. W., Devriendt, K., Flanagan-Steet, H., May, M., Jones, J., Roelens, F., Fons, C., Fernandez, A., Martorell, L., Selicorni, A., Maitz, S., Vitiello, G., Van der Hoeven, G., Skinner, S. A., Bollen, M., Vermeesch, J. R., Steet, R., Van Esch, H. <strong>De novo variants in LMNB1 cause pronounced syndromic microcephaly and disruption of nuclear envelope integrity.</strong> Am. J. Hum. Genet. 107: 753-762, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32910914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32910914</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32910914[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2020.08.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32910914">Cristofoli et al. (2020)</a> identified a de novo heterozygous c.124C-T transition (c.124C-T, NM_005573.3) in exon 1 of the LMNB1 gene, resulting in an arg42-to-trp (R42W) substitution at a highly conserved residue in the coil 1A domain near the head of the protein. The mutation, which was found by trio-based whole-exome sequencing and confirmed by Sanger sequencing, was not present in public databases, including gnomAD. Transfection of the mutant protein into LMNB1-null HeLa cells resulted in abnormal morphology of the nuclear lamina, which appeared diffuse, poorly formed, and with no discrete boundary. There was an increase in multilobed nuclei, which was also observed in patient-derived cells. Mutant LMNB1 was dispersed throughout the cell in the cytoplasm, indicating failure to incorporate into the laminar network; LMNB1 aggregates were often observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32910914" 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 MICROCEPHALY 26, PRIMARY, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMNB1, IVS5DS, 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">rs1751587092 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1751587092;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=rs1751587092" 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=rs1751587092" 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=RCV001254643 OR RCV001292580 OR RCV004032919" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001254643, RCV001292580, RCV004032919" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001254643...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 sibs (P5-P7), born of unrelated Arab parents, with autosomal dominant primary microcephaly-26 (MCPH26; <a href="/entry/619179">619179</a>), <a href="#3" class="mim-tip-reference" title="Cristofoli, F., Moss, T., Moore, H. W., Devriendt, K., Flanagan-Steet, H., May, M., Jones, J., Roelens, F., Fons, C., Fernandez, A., Martorell, L., Selicorni, A., Maitz, S., Vitiello, G., Van der Hoeven, G., Skinner, S. A., Bollen, M., Vermeesch, J. R., Steet, R., Van Esch, H. <strong>De novo variants in LMNB1 cause pronounced syndromic microcephaly and disruption of nuclear envelope integrity.</strong> Am. J. Hum. Genet. 107: 753-762, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32910914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32910914</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32910914[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2020.08.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32910914">Cristofoli et al. (2020)</a> identified a heterozygous G-to-A transition in intron 5 of the LMNB1 gene (c.939+1G-A, NM_005573.3). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was inherited from an unaffected father who was mosaic for the mutation (15% mosaicism). The mutation was predicted to result in a splicing defect, but patient cells were not available for confirmation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32910914" 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 MICROCEPHALY 26, PRIMARY, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
LMNB1, ARG90PRO
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1750506249 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1750506249;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=rs1750506249" 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=rs1750506249" 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=RCV001292581" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001292581" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001292581</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated patients (P10 and P13) with autosomal dominant primary microcephaly-26 (MCPH26; <a href="/entry/619179">619179</a>), <a href="#17" class="mim-tip-reference" title="Parry, D. A., Martin, C.-A., Greene, P., Marsh, J. A., Genomics England Research Consortium, Blyth, M., Cox, H., Donnelly, D., Greenhalgh, L., Greville-Heygate, S., Harrison, V., Lachlan, K., McKenna, C., Quigley, A. J., Rea, G., Robertson, L., Suri, M., Jackson, A. P. <strong>Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy.</strong> Genet. Med. 23: 408-414, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33033404/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33033404</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33033404[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/s41436-020-00980-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33033404">Parry et al. (2021)</a> identified a heterozygous c.269G-C transversion (c.269G-C, NM_005573.4) in the LMNB1 gene, resulting in an arg90-to-pro (R90P) substitution at a highly conserved residue at the interdimer interface of the coil 1B domain. The mutation occurred de novo in P10, whereas parental information was not available for P13. The mutation, which was found by exome sequencing, was not present in the gnomAD database. The location of the mutation was predicted to interfere with dimer or filament assembly, and in vitro functional expression studies in cells transfected with the mutation showed that it caused abnormal LMNB1 nuclear aggregates and an altered nuclear shape. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33033404" 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="Brunetti2014" class="mim-anchor"></a>
|
|
<div class="mim-changed mim-change">
|
|
<p class="mim-text-font">
|
|
Brunetti, V., Ferilli, M. A., Nociti, V., Silvestri, G.
|
|
<strong>Teaching NeuroImages: autosomal dominant leukodystrophy in a sporadic case.</strong>
|
|
Neurology 83: e121, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25224534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25224534</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25224534" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1212/WNL.0000000000000803" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Brussino2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brussino, A., Vaula, G., Cagnoli, C., Mauro, A., Pradotto, L., Daniele, D., Di Gregorio, E., Barberis, M., Arduino, C., Squadrone, S., Abete, M. C., Migone, N., Calabrese, O., Brusco, A.
|
|
<strong>A novel family with lamin B1 duplication associated with adult-onset leucoencephalopathy.</strong>
|
|
J. Neurol. Neurosurg. Psychiat. 80: 237-240, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19151023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19151023</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19151023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jnnp.2008.147330" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Cristofoli2020" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cristofoli, F., Moss, T., Moore, H. W., Devriendt, K., Flanagan-Steet, H., May, M., Jones, J., Roelens, F., Fons, C., Fernandez, A., Martorell, L., Selicorni, A., Maitz, S., Vitiello, G., Van der Hoeven, G., Skinner, S. A., Bollen, M., Vermeesch, J. R., Steet, R., Van Esch, H.
|
|
<strong>De novo variants in LMNB1 cause pronounced syndromic microcephaly and disruption of nuclear envelope integrity.</strong>
|
|
Am. J. Hum. Genet. 107: 753-762, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32910914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32910914</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32910914[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=32910914" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ajhg.2020.08.015" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Dimartino2024" class="mim-anchor"></a>
|
|
<div class="mim-changed mim-change">
|
|
<p class="mim-text-font">
|
|
Dimartino, P., Zadorozhna, M., Yumiceba, V., Basile, A., Cani, I., Melo, U. S., Henck, J., Breur, M., Tonon, C., Lodi, R., Brusco, A., Pippucci, T., and 12 others.
|
|
<strong>Structural variants at the LMNB1 locus: deciphering pathomechanisms in autosomal dominant adult-onset demyelinating leukodystrophy.</strong>
|
|
Ann. Neurol. 96: 855-870, 2024.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/39078102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">39078102</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=39078102" 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/ana.27038" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Dos Santos2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dos Santos, M. M., Grond-Ginsbach, C., Aksay, S. S., Chen, B., Tchatchou, S., Wolf, N. I., van der Knaap, M. S., Grau, A. J.
|
|
<strong>Adult-onset autosomal dominant leukodystrophy due to LMNB1 gene duplication. (Letter)</strong>
|
|
J. Neurol. 259: 579-581, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21909802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21909802</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21909802" 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/s00415-011-6225-4" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Dou2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dou, Z., Xu, C., Donahue, G., Shimi, T., Pan, J.-A., Zhu, J., Ivanov, A., Capell, B. C., Drake, A. M., Shah, P. P., Catanzaro, J. M., Ricketts, M. D., Lamark, T., Adam, S. A., Marmorstein, R., Zong, W.-X., Johansen, T., Goldman, R. D., Adams, P. D., Berger, S. L.
|
|
<strong>Autophagy mediates degradation of nuclear lamina.</strong>
|
|
Nature 527: 105-109, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26524528/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26524528</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26524528[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=26524528" 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/nature15548" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Eldridge1984" class="mim-anchor"></a>
|
|
<div class="mim-changed mim-change">
|
|
<p class="mim-text-font">
|
|
Eldridge, R., Anayiotos, C. P., Schlesinger, S., Cowen, D., Bever, C., Patronas, N., McFarland, H.
|
|
<strong>Hereditary adult-onset leukodystrophy simulating chronic progressive multiple sclerosis.</strong>
|
|
New Eng. J. Med. 311: 948-953, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6472420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6472420</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6472420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM198410113111504" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Furukawa1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Furukawa, K., Hotta, Y.
|
|
<strong>cDNA cloning of a germ cell specific lamin B3 from mouse spermatocytes and analysis of its function by ectopic expression in somatic cells.</strong>
|
|
EMBO J. 12: 97-106, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8094052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8094052</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8094052" 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/j.1460-2075.1993.tb05635.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Furukawa1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Furukawa, K., Inagaki, H., Hotta, Y.
|
|
<strong>Identification and cloning of an mRNA coding for a germ cell-specific A-type lamin in mice.</strong>
|
|
Exp. Cell Res. 212: 426-430, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8187835/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8187835</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8187835" 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/excr.1994.1164" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Giorgio2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giorgio, E., Rolyan, H., Kropp, L., Chakka, A. B., Yatsenko, S., Di Gregorio, E., Lacerenza, D., Vaula, G., Talarico, F., Mandich, P., Toro, C., Pierre, E. E., and 26 others.
|
|
<strong>Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression.</strong>
|
|
Hum. Mutat. 34: 1160-1171, 2013. Note: Erratum: Hum. Mutat. 35: 149 only, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23649844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23649844</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23649844[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=23649844" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.22348" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Goldman2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goldman, R. D., Gruenbaum, Y., Moir, R. D., Shumaker, D. K., Spann, T. P.
|
|
<strong>Nuclear lamins: building blocks of nuclear architecture.</strong>
|
|
Genes Dev. 16: 533-547, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11877373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11877373</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11877373" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1101/gad.960502" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Justice1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Justice, M. J., Gilbert, D. J., Kinzler, K. W., Vogelstein, B., Buchberg, A. M., Ceci, J. D., Matsuda, Y., Chapman, V. M., Patriotis, C., Makris, A., Tsichlis, P. N., Jenkins, N. A., Copeland, N. G.
|
|
<strong>A molecular genetic linkage map of mouse chromosome 18 reveals extensive linkage conservation with human chromosomes 5 and 18.</strong>
|
|
Genomics 13: 1281-1288, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1354644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1354644</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1354644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(92)90047-v" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Kim2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kim, Y., Sharov, A. A., McDole, K., Cheng, M., Hao, H., Fan, C.-M., Gaiano, N., Ko, M. S. H., Zheng, Y.
|
|
<strong>Mouse B-type lamins are required for proper organogenesis but not by embryonic stem cells.</strong>
|
|
Science 334: 1706-1710, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22116031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22116031</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22116031[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=22116031" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1211222" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Lin1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lin, F., Worman, H. J.
|
|
<strong>Structural organization of the human gene (LMNB1) encoding nuclear lamin B1.</strong>
|
|
Genomics 27: 230-236, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7557986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7557986</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7557986" 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.1995.1036" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Maeno1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maeno, H., Sugimoto, K., Nakajima, N.
|
|
<strong>Genomic structure of the mouse gene (Lmnb1) encoding nuclear lamin B1.</strong>
|
|
Genomics 30: 342-346, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8586436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8586436</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8586436" 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.1995.9868" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Padiath2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Padiath, Q. S., Saigoh, K., Schiffmann, R., Asahara, H., Yamada, T., Koeppen, A., Hogan, K., Ptacek, L. J., Fu, Y.-H.
|
|
<strong>Lamin B1 duplications cause autosomal dominant leukodystrophy.</strong>
|
|
Nature Genet. 38: 1114-1123, 2006. Note: Erratum: Nature Genet. 39: 276 only, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16951681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16951681</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16951681" 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/ng1872" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Parry2021" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Parry, D. A., Martin, C.-A., Greene, P., Marsh, J. A., Genomics England Research Consortium, Blyth, M., Cox, H., Donnelly, D., Greenhalgh, L., Greville-Heygate, S., Harrison, V., Lachlan, K., McKenna, C., Quigley, A. J., Rea, G., Robertson, L., Suri, M., Jackson, A. P.
|
|
<strong>Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy.</strong>
|
|
Genet. Med. 23: 408-414, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33033404/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33033404</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33033404[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=33033404" 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/s41436-020-00980-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Pedroso2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pedroso, J. L., Munford, V., Bastos, A. U., Castro, L. P., Marussi, V. H. R., Silva, G. S., Arita, J. H., Menck, C. F. M., Barsottini, O. G.
|
|
<strong>LMNB1 mutation causes cerebellar involvement and a genome instability defect.</strong>
|
|
J. Neurol. Sci. 379: 249-252, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28716252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28716252</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28716252" 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.jns.2017.06.027" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Pollard1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pollard, K. M., Chan, E. K., Grant, B. J., Sullivan, K. E., Tan, E. M., Glass, C. A.
|
|
<strong>In vitro posttranslational modification of lamin B clones from a human T-cell line.</strong>
|
|
Molec. Cell. Biol. 10: 2164-2175, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2325650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2325650</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2325650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/mcb.10.5.2164-2175.1990" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Schuster2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schuster, J., Sundblom, J., Thuresson, A.-C., Hassin-Baer, S., Klopstock, T., Dichgans, M., Cohen, O. S., Raininko, R., Melberg, A., Dahl, N.
|
|
<strong>Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms.</strong>
|
|
Neurogenetics 12: 65-72, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21225301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21225301</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21225301" 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/s10048-010-0269-y" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Tsai2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tsai, M.-Y., Wang, S., Heidinger, J. M., Shumaker, D. K., Adam, S. A., Goldman, R. D., Zheng, Y.
|
|
<strong>A mitotic lamin B matrix induced by RanGTP required for spindle assembly.</strong>
|
|
Science 311: 1887-1893, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16543417/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16543417</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16543417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1122771" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Vergnes2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vergnes, L., Peterfy, M., Bergo, M. O., Young, S. G., Reue, K.
|
|
<strong>Lamin B1 is required for mouse development and nuclear integrity.</strong>
|
|
Proc. Nat. Acad. Sci. 101: 10428-10433, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15232008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15232008</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15232008[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=15232008" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0401424101" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Wydner1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wydner, K. L., McNeil, J. A., Lin, F., Worman, H. J., Lawrence, J. B.
|
|
<strong>Chromosomal assignment of human nuclear envelope protein genes LMNA, LMNB1, and LBR by fluorescence in situ hybridization.</strong>
|
|
Genomics 32: 474-478, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8838815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8838815</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8838815" 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.1996.0146" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 01/16/2025
|
|
</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 : 02/12/2021<br>Ada Hamosh - updated : 1/20/2016<br>Cassandra L. Kniffin - updated : 10/24/2013<br>Cassandra L. Kniffin - updated : 6/5/2012<br>Ada Hamosh - updated : 2/7/2012<br>Victor A. McKusick - updated : 10/26/2006<br>Ada Hamosh - updated : 5/1/2006<br>Anne M. Stumpf - updated : 9/7/2004<br>Victor A. McKusick - updated : 9/1/2004<br>Alan F. Scott - updated : 4/22/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 1/5/1988
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 01/31/2025
|
|
</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 : 01/17/2025<br>ckniffin : 01/16/2025<br>carol : 01/13/2023<br>alopez : 02/19/2021<br>ckniffin : 02/12/2021<br>alopez : 03/18/2016<br>alopez : 1/20/2016<br>alopez : 2/10/2015<br>carol : 2/21/2014<br>carol : 10/28/2013<br>carol : 10/25/2013<br>ckniffin : 10/24/2013<br>alopez : 6/18/2012<br>ckniffin : 6/5/2012<br>alopez : 2/9/2012<br>terry : 2/7/2012<br>alopez : 2/19/2007<br>alopez : 10/27/2006<br>alopez : 10/27/2006<br>terry : 10/26/2006<br>carol : 5/2/2006<br>carol : 5/2/2006<br>terry : 5/1/2006<br>alopez : 9/7/2004<br>alopez : 9/6/2004<br>terry : 9/1/2004<br>mark : 4/25/1996<br>mark : 4/23/1996<br>terry : 4/22/1996<br>mark : 4/22/1996<br>terry : 2/6/1996<br>mark : 1/15/1996<br>carol : 8/14/1992<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>ddp : 10/27/1989<br>marie : 3/25/1988<br>root : 1/28/1988
|
|
</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> 150340
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
LAMIN B1; LMNB1
|
|
|
|
</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">
|
|
LMNB
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: LMNB1</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 448054001;
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 5q23.2
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 5:126,776,623-126,837,020 </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="3">
|
|
<span class="mim-font">
|
|
5q23.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Leukodystrophy, demyelinating, adult-onset, autosomal dominant, atypical
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
621061
|
|
</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">
|
|
Leukodystrophy, demyelinating, adult-onset, autosomal dominant, typical
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
169500
|
|
</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">
|
|
Microcephaly 26, primary, autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
619179
|
|
</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>Lamins are the major components of the nuclear lamina which underlies the nuclear envelope of eukaryotic cells (see lamin A, 150330). Maeno et al. (1995) noted that lamins are members of the intermediate filament protein family. Vertebrate lamins are classified into 2 types, A and B, and mammalian somatic cells show 2 species of each type: lamins A and C for the A type and B1 and B2 for the B type. In addition, germ-cell-specific lamins have been reported for both types (Furukawa and Hotta, 1993 and Furukawa et al., 1994). Whereas A-type lamins are expressed in a developmentally controlled manner, B-type lamins are expressed in all kinds of cells. </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>Pollard et al. (1990) cloned a lamin B cDNA from the human T-cell line MOLT-4. LMNB1 encodes a deduced 586-amino acid protein with a calculated molecular mass of 66,334 Da. The LMNB1 protein shares approximately 72% sequence similarity with lamin A/C (150330). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Lamin B, a component of the interphase nuclear lamina, is required to maintain nuclear shape and mechanical integrity (Goldman et al., 2002). </p><p>Tsai et al. (2006) reported that lamin B has a role in spindle assembly. Lamin B assembled into a matrix-like network in mitosis through a process that depended on the presence of the GTP-bound form of the small guanosine triphosphatase (GTPase) Ran (601179). Depletion of lamin B resulted in defects in spindle assembly. Dominant-negative mutant lamin B proteins that disrupt lamin B assembly in interphase nuclei also disrupted spindle assembly in mitosis. Furthermore, lamin B was essential for the formation of the mitotic matrix that tethers a number of spindle assembly factors. Tsai et al. (2006) proposed that lamin B is a structural component of the long-sought-after spindle matrix that promotes microtubule assembly and organization in mitosis. </p><p>Kim et al. (2011) found that mouse embryonic stem cells do not need any lamins for self-renewal and pluripotency. Although genomewide lamin-B binding profiles correlate with reduced gene expression, such binding is not directly required for gene silencing in embryonic stem cells or trophectoderm cells. However, B-type lamins are required for proper organogenesis. Defects in spindle orientation in neural progenitor cells and migration of neurons probably cause brain disorganizations found in lamin-B-null mice. Kim et al. (2011) concluded that their studies not only disprove several prevailing views of lamin-Bs but also establish a foundation for redefining the function of the nuclear lamina in the context of tissue building and homeostasis. </p><p>Dou et al. (2015) reported that the autophagy machinery mediates degradation of nuclear lamina components in mammals. The autophagy protein LC3/Atg8 (601242), which is involved in autophagy membrane trafficking and substrate delivery, is present in the nucleus and directly interacts with the nuclear lamina protein lamin B1, and binds to lamin-associated domains on chromatin. This LC3-lamin B1 interaction does not downregulate lamin B1 during starvation, but mediates its degradation upon oncogenic insults, such as by activated RAS (see 190020). Lamin B1 degradation is achieved by nucleus-to-cytoplasm transport that delivers lamin B1 to the lysosome. Inhibiting autophagy or the LC3-lamin B1 interaction prevented activated RAS-induced lamin B1 loss and attenuated oncogene-induced senescence in primary human cells. Dou et al. (2015) concluded that this function of autophagy acts as a guarding mechanism protecting cells from tumorigenesis. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Lin and Worman (1995) determined that the human LMNB1 gene contains 11 exons. The transcription unit spans more than 45 kb and the transcription start site is 348 nucleotides upstream from the translation initiation codon. Exon 1 codes for the N-terminal head domain and the first portion of the central rod domain, exons 2 through 6 the central rod domain, and exons 7 through 11 the C-terminal tail domain. Intron positions are conserved in other lamin genes from frogs, mice, and humans but different in lamin genes from Drosophila and C. elegans. </p><p>Maeno et al. (1995) demonstrated that the mouse lamin B1 gene spans about 43 kb of the genome and contains 11 exons, Exon/intron structure of the B1 gene clearly showed the conserved organization among the intermediate filament protein family genes. The presumptive promoter region has high GC content and contains a CAAT box and multiple Sp1 sites but no classical TATA box, suggesting to the authors that the lamin B1 gene has a typical housekeeping gene promoter with a CpG island. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The lamin B gene in the mouse is located on chromosome 18 (Justice et al., 1992) in a region of linkage homology to the long arm of human chromosome 5. Wydner et al. (1996) mapped the human LMNB1 gene to 5q23.3-q31.1 by fluorescence in situ hybridization. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cytogenetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Typical Autosomal Dominant Adult-Onset Demyelinating Leukodystrophy</em></strong></p><p>
|
|
In affected members of a 4 unrelated families, including the large multigenerational Irish family from New Jersey (family K2685) originally reported by Eldridge et al. (1984), with typical autosomal dominant adult-onset demyelinating leukodystrophy (ADLDTY; 169500) Padiath et al. (2006) identified a heterozygous tandem genomic duplication on chromosome 5q23 resulting in an extra copy of the LMNB1 gene. The duplication was identified by sequencing genomic DNA from affected individuals and also from mouse-human hybrid cell lines derived from cells of affected individuals. The duplications segregated with the disorder in the families. The hybrid cell lines enabled Padiath et al. (2006) to separate chromosomes derived from each of the 2 parents of an individual and to assign phase unambiguously when identifying sequencing variants. They constructed a haplotype map of the chromosome carrying the disease-causing mutation and observed a large shared haplotype block in the critical region in 2 families, suggesting a common founder. The other 2 families each carried unique duplications. Increased expression of lamin B1 in Drosophila melanogaster resulted in a degenerative phenotype. In addition, an abnormal nuclear morphology was apparent when cultured cells overexpressed this protein. Antibodies to lamin B are found in individuals with autoimmune diseases, and it is also an antigen recognized by a monoclonal antibody raised against plaques from brains of individuals with multiple sclerosis (126200). This raised the possibility that lamin B may be a link to the autoimmune attack that occurs in multiple sclerosis. </p><p>Brussino et al. (2009) found a 140- to 190-kb duplication of 5q including the entire LMNB1 gene, the AX748201 transcript, and the 3-prime end of the MARCH3 gene (613333) in 1 of 8 Italian probands with adult-onset leukoencephalopathy. The patient's affected cousin also carried the duplication, and there was a family history of a similar disorder. Lamin B1 expression was increased in lymphoblasts from one of the patients with the duplication. </p><p>In affected members of 4 unrelated families with typical ADLD, Schuster et al. (2011) found heterozygous duplications involving the LMNB1 gene. All 4 duplications were of different sizes, ranging from 107 to 218 kb, supporting independent events. Five patients from 2 families had about a 2-fold increased level of LMNB1 protein in white blood cells, and LMNB1 mRNA was also increased compared to controls. Each duplication extended over part of the MARCH3 gene, but MARCH3 mRNA was not increased in patient leukocytes. Schuster et al. (2011) concluded that an accurate molecular diagnosis of the disorder could be made by direct analysis of LMNB1 in peripheral leukocytes. </p><p>In a symptomatic man with ADLD and his asymptomatic sister who had leukodystrophy on brain imaging, Dos Santos et al. (2012) identified a heterozygous 148-kb duplication on chromosome 5q23.2 including the LMNB1 gene, but not the MARCH3 gene. </p><p>Using a custom array, Giorgio et al. (2013) performed detailed breakpoint junction sequence analysis of the duplicated 5q23 region containing the LMNB1 gene in 20 independent families with ADLD in whom genomic LMNB1 duplication was initially identified by aCGH, QT-PCR, or MLPA. Seven families had previously been reported (Brussino et al., 2009; Schuster et al., 2011; Dos Santos et al., 2012). There were a total of 16 unique heterozygous rearrangements. Three of the duplications were shared by more than 1 family: 1 was found in 3 families and the other 2 duplications were found in 2 families each. Individuals with identical junctions shared the same haplotype, consistent with a founder effect. Duplication sizes ranged from about 128 kb to 475 kb. The largest duplication also included the PHAX (604924), ALDH7A1 (107323), and GRAMD3 (GRAMD2B; 620182) genes. Comparison of all the samples identified a 72-kb minimal critical duplicated region required for ADLD that contained only the LMNB1 gene. All but 1 of the duplications were in the direct tandem orientation; the remaining duplication was inverted (see ADLDAT, 621061). Characterization of the junction sequences showed that most (11 of 15) showed short stretches of microhomology overlap ranging from 1 to 6 nucleotides, whereas the others showed small insertions at the breakpoints. All duplications resulted from intrachromosomal rearrangements. Analysis of the genomic architecture suggested several potential mechanisms for the duplications, including nonhomologous end joining (NHEJ) or fork stalling and template switching/microhomology-mediated break-induced repair (FoSTeS/MMBIR). The enrichment of Alu repetitive elements at the centromeric breakpoints (found in 4 cases), higher GC content, and high frequency of repetitive sequences at breakpoints likely also played a role in mediating ADLD duplications. RT-PCR of patients fibroblasts or blood showed increased LMNB1 expression (2.1- to 4.8-fold compared to controls), as well as increased protein levels (1.6- to 3.2-fold compared to controls). There was no apparent difference in phenotype according to duplication size. </p><p>Using high-throughput chromosome conformation capture (Hi-C) techniques to analyze topologically associating domains (TADs), Dimartino et al. (2024) found that patients with typical ADLD (Giorgio et al., 2013; Brunetti et al., 2014) carried intra-TAD duplications on 5q23 within the LMNB1 TAD that did not extend beyond TAD boundaries and maintained the physiologic regulatory context of LMNB1. This resulted in overexpression of the LMNB1 gene. The authors concluded that duplication of the LMNB1 gene per se is not causative of typical ADLD, which will affect ADLD diagnosis and genetic counseling. </p><p>See also atypical autosomal dominant adult-onset demyelinating leukodystrophy (ADLDAT; 621061), which is caused by heterozygous deletions of chromosome 5q23 involving regulatory regions upstream of the LMNB1 gene.</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>Autosomal Dominant Primary Microcephaly 26</em></strong></p><p>
|
|
In 7 patients from 5 unrelated families with autosomal dominant primary microcephaly-26 (MCPH26; 619179), Cristofoli et al. (2020) identified heterozygous mutations in the LMNB1 gene (150340.0002-150340.0006). The mutations were found by whole-exome sequencing or microarray analysis and confirmed by Sanger sequencing. The mutations occurred de novo in 3 patients, whereas 1 was inherited from a mildly affected mother, and in 3 sibs were inherited from an unaffected father who was mosaic for the mutation. There was 1 intragenic deletion, 1 splice site mutation, and 3 missense variants affecting highly conserved residues. In vitro functional expression studies of the 3 missense variants showed that they caused variable abnormalities of the nuclear lamina and misshapen nuclei. One was associated with decreased protein expression, and the others caused mislocalization of LMNB1 to the cytoplasm. However, mitotic spindle formation and mitotic segregation did not appear to be affected. The authors postulated a dominant-negative effect. </p><p>In 7 unrelated patients (P1-P3, P9-P11, P13) with MCPH26, Parry et al. (2021) identified heterozygous mutations in the LMNB1 gene (see, e.g., 150340.0004 and 150340.0007). There were 2 recurrent missense mutations and an in-frame deletion; none were present in the gnomAD database. The mutations occurred de novo in all patients for whom parental material was available. The location of the mutations predicted interference with dimer or filament assembly, and in vitro functional expression studies in cells transfected with the mutations showed that they caused abnormal LMNB1 nuclear aggregates and an altered nuclear shape. Parry et al. (2021) postulated that the mutations may alter the properties of lamin filaments, resulting in fragile nuclei that are susceptible to the mechanical stresses of nuclear and neuronal migration, leading to increased cell death during brain development. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
In a 42-year-old woman of Italian ancestry, who was born in Brazil, with clinical features of ADLD, Pedroso et al. (2017) identified a heterozygous missense variant in the LMNB1 gene (R29W). The variant, which was found by whole-exome sequencing, was not present in several public databases, including the Exome Sequencing Project and ExAC. Patient-derived cells showed increased expression of variant LMNB1 mRNA, as well as nuclear structural abnormalities. Functional studies demonstrated an impaired response to DNA damage, suggesting genomic instability. The patient presented at 23 years of age with progressive cerebellar atrophy and cognitive impairment. Brain imaging showed white matter abnormalities in the cerebellum, as well as atrophy of the corpus callosum, brainstem, and spinal cord. In in vitro studies, Cristofoli et al. (2020) demonstrated that the R29W variant was present in the nuclear extract, suggesting that it did not disrupt nuclear lamina localization of LMNB1. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Mutations affecting A-type lamins have been associated with a variety of human diseases, including muscular dystrophy (e.g., 181350), cardiomyopathy (e.g., 115200), lipodystrophy (e.g., 151660), and progeria (176670), but mutations in B-type lamins had not been identified in humans or in experimental animals. To investigate the in vivo function of lamin B1, Vergnes et al. (2004) generated mice with an insertional mutation in Lmnb1. The mutation resulted in the synthesis of a mutant lamin B1 protein lacking several key functional domains, including a portion of the rod domain, the nuclear localization signal, and the CAAX motif (the C-terminal signal for farnesylation). Homozygous Lmnb1 mutant mice survived embryonic development but died at birth with defects in lung and bone. Fibroblasts from mutant embryos grew under standard cell culture conditions but displayed grossly misshapen nuclei, impaired differentiation, increased polyploidy, and premature senescence. Thus, the lamin B1 mutant mice provided evidence for a broad and nonredundant function of lamin B1 in mammalian development. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>7 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-text-font">
|
|
<strong>.0001 MOVED TO CYTOGENETICS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 MICROCEPHALY 26, PRIMARY, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNB1, ALA152GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs935132421,
|
|
|
|
|
|
|
|
ClinVar: RCV001254640, RCV001292576
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 10-year-old boy (P1), born of unrelated Belgian parents, with autosomal dominant primary microcephaly-26 (MCPH26; 619179), Cristofoli et al. (2020) identified a de novo heterozygous c.455C-G transversion (c.455C-G, NM_005573.3) in exon 2 of the LMNB1 gene, resulting in an ala152-to-gly (A152G) substitution at a highly conserved residue in the coil 1B domain. The mutation, which was found by trio-based whole-exome sequencing and confirmed by Sanger sequencing, was not present in public databases, including gnomAD. Patient cells showed decreased levels of the mutant protein. Transfection of the mutant protein into LMNB1-null HeLa cells also resulted in reduced protein levels, suggesting possible instability of the mutant protein, although further studies did not show increased turnover of the A152G protein compared to controls. The A152G variant caused abnormalities in the nuclear lamina, including abnormal and irregular ruffling, suggesting global disruption of the nuclear envelope. There was an increase in the percentage of cells with condensed nuclei, which may have been a result of overexpression. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 MICROCEPHALY 26, PRIMARY, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNB1, EX6-8 DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV001254644, RCV002287475
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 9-year-old Belgian girl (P2) with autosomal dominant primary microcephaly-26 (MCPH26; 619179), Cristofoli et al. (2020) identified a heterozygous in-frame deletion in the LMNB1 gene, causing the deletion of exons 6-8 (Ser314_Thr497del). The deletion, which was found by microarray analysis, was inherited from the similarly affected mother in whom it occurred de novo. The deletion was predicted to result in a shortened protein lacking the nuclear localization signal. The authors postulated that the mutation results in insufficient protein abundance in the nucleus to form a stable laminar network and acts in a dominant-negative manner. However, functional studies of the variant and studies of patient cells were not performed. These patients had a milder phenotype than the others: the proband had a head circumference (HC) of -3.6 SD, whereas her mother had a HC of -2.5 SD and had learning difficulties. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 MICROCEPHALY 26, PRIMARY, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNB1, LYS33GLU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1750497172,
|
|
|
|
|
|
|
|
ClinVar: RCV001254641, RCV001292578, RCV002558702
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old Italian girl (P3) with autosomal dominant primary microcephaly-26 (MCPH26; 619179), Cristofoli et al. (2020) identified a de novo heterozygous c.97A-G transition (c.97A-G, NM_005573.3) in exon 1 of the LMNB1 gene, resulting in a lys33-to-glu (K33E) substitution at a highly conserved residue in the coil 1A domain near the head of the protein. The mutation, which was found by trio-based whole-exome sequencing and confirmed by Sanger sequencing, was not present in public databases, including gnomAD. Transfection of the mutant protein into LMNB1-null HeLa cells resulted in abnormal morphology of the nuclear lamina, which appeared diffuse, poorly formed, and with no discrete boundary. There was an increase in multilobed nuclei, which was also observed in patient-derived cells. Mutant LMNB1 was dispersed throughout the cell in the cytoplasm, indicating failure to incorporate into the laminar network; LMNB1 aggregates were often observed. </p><p>In 3 unrelated patients (P1, P9, and P11) with MCPH26, Parry et al. (2021) identified a de novo heterozygous K33E mutation in the LMNB1 gene. The location of the mutation was predicted to interfere with dimer or filament assembly, and in vitro functional expression studies in cells transfected with the mutant protein showed that it caused abnormal LMNB1 nuclear aggregates and an altered nuclear shape. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 MICROCEPHALY 26, PRIMARY, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNB1, ARG42TRP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1245844735,
|
|
|
|
|
|
gnomAD: rs1245844735,
|
|
|
|
|
|
ClinVar: RCV001254642, RCV001292579, RCV003148939
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-year-old girl (P4) with autosomal dominant primary microcephaly-26 (MCPH26; 619179), Cristofoli et al. (2020) identified a de novo heterozygous c.124C-T transition (c.124C-T, NM_005573.3) in exon 1 of the LMNB1 gene, resulting in an arg42-to-trp (R42W) substitution at a highly conserved residue in the coil 1A domain near the head of the protein. The mutation, which was found by trio-based whole-exome sequencing and confirmed by Sanger sequencing, was not present in public databases, including gnomAD. Transfection of the mutant protein into LMNB1-null HeLa cells resulted in abnormal morphology of the nuclear lamina, which appeared diffuse, poorly formed, and with no discrete boundary. There was an increase in multilobed nuclei, which was also observed in patient-derived cells. Mutant LMNB1 was dispersed throughout the cell in the cytoplasm, indicating failure to incorporate into the laminar network; LMNB1 aggregates were often observed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MICROCEPHALY 26, PRIMARY, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNB1, IVS5DS, G-A, +1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1751587092,
|
|
|
|
|
|
|
|
ClinVar: RCV001254643, RCV001292580, RCV004032919
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 sibs (P5-P7), born of unrelated Arab parents, with autosomal dominant primary microcephaly-26 (MCPH26; 619179), Cristofoli et al. (2020) identified a heterozygous G-to-A transition in intron 5 of the LMNB1 gene (c.939+1G-A, NM_005573.3). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was inherited from an unaffected father who was mosaic for the mutation (15% mosaicism). The mutation was predicted to result in a splicing defect, but patient cells were not available for confirmation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MICROCEPHALY 26, PRIMARY, AUTOSOMAL DOMINANT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
LMNB1, ARG90PRO
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1750506249,
|
|
|
|
|
|
|
|
ClinVar: RCV001292581
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated patients (P10 and P13) with autosomal dominant primary microcephaly-26 (MCPH26; 619179), Parry et al. (2021) identified a heterozygous c.269G-C transversion (c.269G-C, NM_005573.4) in the LMNB1 gene, resulting in an arg90-to-pro (R90P) substitution at a highly conserved residue at the interdimer interface of the coil 1B domain. The mutation occurred de novo in P10, whereas parental information was not available for P13. The mutation, which was found by exome sequencing, was not present in the gnomAD database. The location of the mutation was predicted to interfere with dimer or filament assembly, and in vitro functional expression studies in cells transfected with the mutation showed that it caused abnormal LMNB1 nuclear aggregates and an altered nuclear shape. </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">
|
|
Brunetti, V., Ferilli, M. A., Nociti, V., Silvestri, G.
|
|
<strong>Teaching NeuroImages: autosomal dominant leukodystrophy in a sporadic case.</strong>
|
|
Neurology 83: e121, 2014.
|
|
|
|
|
|
[PubMed: 25224534]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1212/WNL.0000000000000803]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brussino, A., Vaula, G., Cagnoli, C., Mauro, A., Pradotto, L., Daniele, D., Di Gregorio, E., Barberis, M., Arduino, C., Squadrone, S., Abete, M. C., Migone, N., Calabrese, O., Brusco, A.
|
|
<strong>A novel family with lamin B1 duplication associated with adult-onset leucoencephalopathy.</strong>
|
|
J. Neurol. Neurosurg. Psychiat. 80: 237-240, 2009.
|
|
|
|
|
|
[PubMed: 19151023]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jnnp.2008.147330]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cristofoli, F., Moss, T., Moore, H. W., Devriendt, K., Flanagan-Steet, H., May, M., Jones, J., Roelens, F., Fons, C., Fernandez, A., Martorell, L., Selicorni, A., Maitz, S., Vitiello, G., Van der Hoeven, G., Skinner, S. A., Bollen, M., Vermeesch, J. R., Steet, R., Van Esch, H.
|
|
<strong>De novo variants in LMNB1 cause pronounced syndromic microcephaly and disruption of nuclear envelope integrity.</strong>
|
|
Am. J. Hum. Genet. 107: 753-762, 2020.
|
|
|
|
|
|
[PubMed: 32910914]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2020.08.015]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dimartino, P., Zadorozhna, M., Yumiceba, V., Basile, A., Cani, I., Melo, U. S., Henck, J., Breur, M., Tonon, C., Lodi, R., Brusco, A., Pippucci, T., and 12 others.
|
|
<strong>Structural variants at the LMNB1 locus: deciphering pathomechanisms in autosomal dominant adult-onset demyelinating leukodystrophy.</strong>
|
|
Ann. Neurol. 96: 855-870, 2024.
|
|
|
|
|
|
[PubMed: 39078102]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ana.27038]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dos Santos, M. M., Grond-Ginsbach, C., Aksay, S. S., Chen, B., Tchatchou, S., Wolf, N. I., van der Knaap, M. S., Grau, A. J.
|
|
<strong>Adult-onset autosomal dominant leukodystrophy due to LMNB1 gene duplication. (Letter)</strong>
|
|
J. Neurol. 259: 579-581, 2012.
|
|
|
|
|
|
[PubMed: 21909802]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00415-011-6225-4]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dou, Z., Xu, C., Donahue, G., Shimi, T., Pan, J.-A., Zhu, J., Ivanov, A., Capell, B. C., Drake, A. M., Shah, P. P., Catanzaro, J. M., Ricketts, M. D., Lamark, T., Adam, S. A., Marmorstein, R., Zong, W.-X., Johansen, T., Goldman, R. D., Adams, P. D., Berger, S. L.
|
|
<strong>Autophagy mediates degradation of nuclear lamina.</strong>
|
|
Nature 527: 105-109, 2015.
|
|
|
|
|
|
[PubMed: 26524528]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature15548]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eldridge, R., Anayiotos, C. P., Schlesinger, S., Cowen, D., Bever, C., Patronas, N., McFarland, H.
|
|
<strong>Hereditary adult-onset leukodystrophy simulating chronic progressive multiple sclerosis.</strong>
|
|
New Eng. J. Med. 311: 948-953, 1984.
|
|
|
|
|
|
[PubMed: 6472420]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM198410113111504]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Furukawa, K., Hotta, Y.
|
|
<strong>cDNA cloning of a germ cell specific lamin B3 from mouse spermatocytes and analysis of its function by ectopic expression in somatic cells.</strong>
|
|
EMBO J. 12: 97-106, 1993.
|
|
|
|
|
|
[PubMed: 8094052]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1993.tb05635.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Furukawa, K., Inagaki, H., Hotta, Y.
|
|
<strong>Identification and cloning of an mRNA coding for a germ cell-specific A-type lamin in mice.</strong>
|
|
Exp. Cell Res. 212: 426-430, 1994.
|
|
|
|
|
|
[PubMed: 8187835]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/excr.1994.1164]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giorgio, E., Rolyan, H., Kropp, L., Chakka, A. B., Yatsenko, S., Di Gregorio, E., Lacerenza, D., Vaula, G., Talarico, F., Mandich, P., Toro, C., Pierre, E. E., and 26 others.
|
|
<strong>Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression.</strong>
|
|
Hum. Mutat. 34: 1160-1171, 2013. Note: Erratum: Hum. Mutat. 35: 149 only, 2014.
|
|
|
|
|
|
[PubMed: 23649844]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.22348]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goldman, R. D., Gruenbaum, Y., Moir, R. D., Shumaker, D. K., Spann, T. P.
|
|
<strong>Nuclear lamins: building blocks of nuclear architecture.</strong>
|
|
Genes Dev. 16: 533-547, 2002.
|
|
|
|
|
|
[PubMed: 11877373]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gad.960502]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Justice, M. J., Gilbert, D. J., Kinzler, K. W., Vogelstein, B., Buchberg, A. M., Ceci, J. D., Matsuda, Y., Chapman, V. M., Patriotis, C., Makris, A., Tsichlis, P. N., Jenkins, N. A., Copeland, N. G.
|
|
<strong>A molecular genetic linkage map of mouse chromosome 18 reveals extensive linkage conservation with human chromosomes 5 and 18.</strong>
|
|
Genomics 13: 1281-1288, 1992.
|
|
|
|
|
|
[PubMed: 1354644]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(92)90047-v]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kim, Y., Sharov, A. A., McDole, K., Cheng, M., Hao, H., Fan, C.-M., Gaiano, N., Ko, M. S. H., Zheng, Y.
|
|
<strong>Mouse B-type lamins are required for proper organogenesis but not by embryonic stem cells.</strong>
|
|
Science 334: 1706-1710, 2011.
|
|
|
|
|
|
[PubMed: 22116031]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1211222]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lin, F., Worman, H. J.
|
|
<strong>Structural organization of the human gene (LMNB1) encoding nuclear lamin B1.</strong>
|
|
Genomics 27: 230-236, 1995.
|
|
|
|
|
|
[PubMed: 7557986]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1995.1036]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maeno, H., Sugimoto, K., Nakajima, N.
|
|
<strong>Genomic structure of the mouse gene (Lmnb1) encoding nuclear lamin B1.</strong>
|
|
Genomics 30: 342-346, 1995.
|
|
|
|
|
|
[PubMed: 8586436]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1995.9868]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Padiath, Q. S., Saigoh, K., Schiffmann, R., Asahara, H., Yamada, T., Koeppen, A., Hogan, K., Ptacek, L. J., Fu, Y.-H.
|
|
<strong>Lamin B1 duplications cause autosomal dominant leukodystrophy.</strong>
|
|
Nature Genet. 38: 1114-1123, 2006. Note: Erratum: Nature Genet. 39: 276 only, 2007.
|
|
|
|
|
|
[PubMed: 16951681]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1872]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Parry, D. A., Martin, C.-A., Greene, P., Marsh, J. A., Genomics England Research Consortium, Blyth, M., Cox, H., Donnelly, D., Greenhalgh, L., Greville-Heygate, S., Harrison, V., Lachlan, K., McKenna, C., Quigley, A. J., Rea, G., Robertson, L., Suri, M., Jackson, A. P.
|
|
<strong>Heterozygous lamin B1 and lamin B2 variants cause primary microcephaly and define a novel laminopathy.</strong>
|
|
Genet. Med. 23: 408-414, 2021.
|
|
|
|
|
|
[PubMed: 33033404]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41436-020-00980-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pedroso, J. L., Munford, V., Bastos, A. U., Castro, L. P., Marussi, V. H. R., Silva, G. S., Arita, J. H., Menck, C. F. M., Barsottini, O. G.
|
|
<strong>LMNB1 mutation causes cerebellar involvement and a genome instability defect.</strong>
|
|
J. Neurol. Sci. 379: 249-252, 2017.
|
|
|
|
|
|
[PubMed: 28716252]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.jns.2017.06.027]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pollard, K. M., Chan, E. K., Grant, B. J., Sullivan, K. E., Tan, E. M., Glass, C. A.
|
|
<strong>In vitro posttranslational modification of lamin B clones from a human T-cell line.</strong>
|
|
Molec. Cell. Biol. 10: 2164-2175, 1990.
|
|
|
|
|
|
[PubMed: 2325650]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/mcb.10.5.2164-2175.1990]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schuster, J., Sundblom, J., Thuresson, A.-C., Hassin-Baer, S., Klopstock, T., Dichgans, M., Cohen, O. S., Raininko, R., Melberg, A., Dahl, N.
|
|
<strong>Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms.</strong>
|
|
Neurogenetics 12: 65-72, 2011.
|
|
|
|
|
|
[PubMed: 21225301]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10048-010-0269-y]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tsai, M.-Y., Wang, S., Heidinger, J. M., Shumaker, D. K., Adam, S. A., Goldman, R. D., Zheng, Y.
|
|
<strong>A mitotic lamin B matrix induced by RanGTP required for spindle assembly.</strong>
|
|
Science 311: 1887-1893, 2006.
|
|
|
|
|
|
[PubMed: 16543417]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1122771]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vergnes, L., Peterfy, M., Bergo, M. O., Young, S. G., Reue, K.
|
|
<strong>Lamin B1 is required for mouse development and nuclear integrity.</strong>
|
|
Proc. Nat. Acad. Sci. 101: 10428-10433, 2004.
|
|
|
|
|
|
[PubMed: 15232008]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0401424101]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wydner, K. L., McNeil, J. A., Lin, F., Worman, H. J., Lawrence, J. B.
|
|
<strong>Chromosomal assignment of human nuclear envelope protein genes LMNA, LMNB1, and LBR by fluorescence in situ hybridization.</strong>
|
|
Genomics 32: 474-478, 1996.
|
|
|
|
|
|
[PubMed: 8838815]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1996.0146]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 01/16/2025<br>Cassandra L. Kniffin - updated : 02/12/2021<br>Ada Hamosh - updated : 1/20/2016<br>Cassandra L. Kniffin - updated : 10/24/2013<br>Cassandra L. Kniffin - updated : 6/5/2012<br>Ada Hamosh - updated : 2/7/2012<br>Victor A. McKusick - updated : 10/26/2006<br>Ada Hamosh - updated : 5/1/2006<br>Anne M. Stumpf - updated : 9/7/2004<br>Victor A. McKusick - updated : 9/1/2004<br>Alan F. Scott - updated : 4/22/1996
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 1/5/1988
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 01/31/2025<br>alopez : 01/17/2025<br>ckniffin : 01/16/2025<br>carol : 01/13/2023<br>alopez : 02/19/2021<br>ckniffin : 02/12/2021<br>alopez : 03/18/2016<br>alopez : 1/20/2016<br>alopez : 2/10/2015<br>carol : 2/21/2014<br>carol : 10/28/2013<br>carol : 10/25/2013<br>ckniffin : 10/24/2013<br>alopez : 6/18/2012<br>ckniffin : 6/5/2012<br>alopez : 2/9/2012<br>terry : 2/7/2012<br>alopez : 2/19/2007<br>alopez : 10/27/2006<br>alopez : 10/27/2006<br>terry : 10/26/2006<br>carol : 5/2/2006<br>carol : 5/2/2006<br>terry : 5/1/2006<br>alopez : 9/7/2004<br>alopez : 9/6/2004<br>terry : 9/1/2004<br>mark : 4/25/1996<br>mark : 4/23/1996<br>terry : 4/22/1996<br>mark : 4/22/1996<br>terry : 2/6/1996<br>mark : 1/15/1996<br>carol : 8/14/1992<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>ddp : 10/27/1989<br>marie : 3/25/1988<br>root : 1/28/1988
|
|
</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>
|
|
|
|
|